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Hematocrit in sickle cell anemia: What are the typical baseline blood study abnormalities in patients with sickle cell disease (SCD)?

Содержание

What are the typical baseline blood study abnormalities in patients with sickle cell disease (SCD)?

Author

Joseph E Maakaron, MD Research Fellow, Department of Internal Medicine, Division of Hematology/Oncology, American University of Beirut Medical Center, Lebanon

Disclosure: Nothing to disclose.

Coauthor(s)

Ali T Taher, MD, PhD, FRCP Professor of Medicine, Associate Chair of Research, Department of Internal Medicine, Division of Hematology/Oncology, Director of Research, NK Basile Cancer Center, American University of Beirut Medical Center, Lebanon

Disclosure: Nothing to disclose.

Specialty Editor Board

Jeanne Yu, PharmD 

Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Acknowledgements

Roy Alson, MD, PhD, FACEP, FAAEM Associate Professor, Department of Emergency Medicine, Wake Forest University School of Medicine; Medical Director, Forsyth County EMS; Deputy Medical Advisor, North Carolina Office of EMS; Associate Medical Director, North Carolina Baptist AirCare

Roy Alson, MD, PhD, FACEP, FAAEM is a member of the following medical societies: Air Medical Physician Association, American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, National Association of EMS Physicians, North Carolina Medical Society, Society for Academic Emergency Medicine, and World Association for Disaster and Emergency Medicine

Disclosure: Nothing to disclose.

Jeffrey L Arnold, MD, FACEP Chairman, Department of Emergency Medicine, Santa Clara Valley Medical Center

Jeffrey L Arnold, MD, FACEP is a member of the following medical societies: American Academy of Emergency Medicine and American College of Physicians

Disclosure: Nothing to disclose.

Robert J Arceci, MD, PhD King Fahd Professor of Pediatric Oncology, Professor of Pediatrics, Oncology and the Cellular and Molecular Medicine Graduate Program, Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine

Robert J Arceci, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Pediatric Society, American Society of Hematology, and American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Wadie F Bahou, MD Chief, Division of Hematology, Hematology/Oncology Fellowship Director, Professor, Department of Internal Medicine, State University of New York at Stony Brook

Wadie F Bahou, MD is a member of the following medical societies: American Society of Hematology

Disclosure: Nothing to disclose.

Dvorah Balsam, MD Chief, Division of Pediatric Radiology, Nassau University Medical Center; Professor, Department of Clinical Radiology, State University of New York at Stony Brook

Disclosure: Nothing to disclose.

Salvatore Bertolone, MD Director, Division of Pediatric Hematology/Oncology, Department of Pediatrics, Kosair Children’s Hospital; Professor, University of Louisville School of Medicine

Salvatore Bertolone, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Education, American Association of Blood Banks, American Cancer Society, American Society of Hematology, American Society of Pediatric Hematology/Oncology, and Kentucky Medical Association

Disclosure: Nothing to disclose.

Barry E Brenner, MD, PhD, FACEP Professor of Emergency Medicine, Professor of Internal Medicine, Program Director, Emergency Medicine, Case Medical Center, University Hospitals, Case Western Reserve University School of Medicine

Barry E Brenner, MD, PhD, FACEP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Chest Physicians, American College of Emergency Physicians, American College of Physicians, American Heart Association, American Thoracic Society, Arkansas Medical Society, New York Academy of Medicine, New York Academy of Sciences,and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Marcel E Conrad, MD Distinguished Professor of Medicine (Retired), University of South Alabama College of Medicine

Marcel E Conrad, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Association of Blood Banks, American Chemical Society, American College of Physicians, American Physiological Society, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, Association of Military Surgeons of the US, International Society of Hematology, Society for Experimental Biology and Medicine, and Southwest Oncology Group

Disclosure: No financial interests None None

Nedra R Dodds, MD Medical Director, Opulence Aesthetic Medicine

Nedra R Dodds, MD is a member of the following medical societies: American Academy of Anti-Aging Medicine, American Academy of Cosmetic Surgery, American College of Emergency Physicians, American Medical Association, National Medical Association, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

James L Harper, MD Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Assistant Clinical Professor, Department of Pediatrics, Creighton University School of Medicine; Director, Continuing Medical Education, Children’s Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center

James L Harper, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Federation for Clinical Research, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Council on Medical Student Education in Pediatrics, and Hemophilia and Thrombosis Research Society

Disclosure: Nothing to disclose.

Adlette Inati, MD Head, Division of Pediatric Hematology-Oncology, Medical Director, Children’s Center for Cancer and Blood Diseases, Rafik Hariri University Hospital; Research Associate, Balamand University; Head of Post Bone Marrow Transplant Clinic and Consultant Hematologist, Chronic Care Center; Founding Faculty, Lebanese American University School of Medicine, Lebanon

Adlette Inati, MD is a member of the following medical societies: Alpha Omega Alpha, American Society of Hematology, European Hematology Association, and International Society of Hematology

Disclosure: Nothing to disclose.

Ziad N Kazzi, MD Assistant Professor, Department of Emergency Medicine, Emory University; Medical Toxicologist, Georgia Poison Center

Ziad N Kazzi, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American College of Emergency Physicians, and American College of Medical Toxicology

Disclosure: Nothing to disclose.

Richard S Krause, MD Senior Clinical Faculty/Clinical Assistant Professor, Department of Emergency Medicine, University of Buffalo State University of New York School of Medicine and Biomedical Sciences

Richard S Krause, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Ashok B Raj, MD Associate Professor, Section of Pediatric Hematology and Oncology, Department of Pediatrics, Kosair Children’s Hospital, University of Louisville School of Medicine

Ashok B Raj, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Pediatric Hematology/Oncology, Children’s Oncology Group, and Kentucky Medical Association

Disclosure: Nothing to disclose.

Sharada A Sarnaik, MBBS Professor of Pediatrics, Wayne State University School of Medicine; Director, Sickle Cell Center, Attending Hematologist/Oncologist, Children’s Hospital of Michigan

Sharada A Sarnaik, MBBS is a member of the following medical societies: American Association of Blood Banks, American Association of University Professors, American Society of Hematology, American Society of Pediatric Hematology/Oncology, New York Academy of Sciences, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Hosseinali Shahidi, MD, MPH Assistant Professor, Departments of Emergency Medicine and Pediatrics, State University of New York and Health Science Center at Brooklyn

Hosseinali Shahidi, MD, MPH is a member of the following medical societies: American Academy of Pediatrics, American College of Emergency Physicians, and American Public Health Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Garry Wilkes MBBS, FACEM, Director of Emergency Medicine, Calvary Hospital, Canberra, ACT; Adjunct Associate Professor, Edith Cowan University; Clinical Associate Professor, Rural Clinical School, University of Western Australia

Disclosure: Nothing to disclose.

Mary L Windle, PharmD, Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Ulrich Josef Woermann, MD Consulting Staff, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland

Disclosure: Nothing to disclose.

Grace M Young, MD Associate Professor, Department of Pediatrics, University of Maryland Medical Center

Grace M Young, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Emergency Physicians

Disclosure: Nothing to disclose.

Blood counts and sickle cell disease

What are blood counts?

Blood is made up of cells in a liquid called plasma. Blood cells are made in the bone marrow (the soft center of the bones). Then they are released into the body to do their jobs. The body has 3 main types of blood cells: red blood cells, white blood cells, and platelets. Sickle cell disease mainly affects the red blood cells, but can sometimes affect other blood cells. Medicines for sickle cell disease can also affect blood cells.  

If your child has sickle cell disease, counting and studying blood cells can tell the St. Jude staff about your child’s disease and how to treat it. A complete blood count (CBC) is a test that tells your child’s doctor about all 3 types of blood cells: red blood cells, platelets, and white blood cells.

Red blood cells

The main purpose of red blood cells is to deliver oxygen to the body. The part of the blood that carries oxygen is called hemoglobin. People with sickle cell disease have abnormal hemoglobin, called sickle hemoglobin or hemoglobin S. If your child has sickle cell disease, her red blood cells do not last as long because the sickle hemoglobin damages them. This means your child has fewer red blood cells than normal, a condition called anemia. People with normal hemoglobin usually have a hemoglobin level around 12 g/dL. People with sickle cell disease have lower hemoglobin levels, usually between 6–11 g/dL. The exact level may be different depending on the type of sickle cell disease and the person. It is important to know your child’s usual hemoglobin level. Blood tests done over a period of time will tell the doctor what is normal for your child. 

Reticulocyte count

A reticulocyte is a young red blood cell that is forming in the bone marrow. Normally, reticulocytes stay in the bone marrow until they develop into red blood cells and enter the blood. The reticulocyte count is a test that measures the number of reticulocytes in the blood. For most people, the number is very low because most reticulocytes stay in the bone marrow. If your child has sickle cell disease, she may have a higher reticulocyte count. This is because your child’s body has to make more red blood cells due to anemia. A normal amount of reticulocytes in the blood is between 0.45–1.8 percent. If your child has sickle cell disease, she may have a reticulocyte count of 2–3 percent or more.  The number of reticulocytes is different for each person with sickle cell disease.  If your child’s reticulocyte count drops very much, it might mean her body is making fewer red blood cells. This could be dangerous. The St. Jude staff will test your child’s reticulocyte count at each clinic visit.

White blood cells

White blood cells help the body fight infection. A normal white blood cell count is 5,000–10,000/mm3. When the white blood cell count is low, it is easier to get an infection and harder to get over it. If your child has sickle cell disease, her white blood cell count will usually be normal or higher than normal. However, illness and some medicines can make the white blood cell count go up or down for a short time.  

Neutropenia

A neutrophil is a type of white blood cell that kills bacteria. Neutrophils help prevent infection.  If your child does not have enough neutrophils, this is called neutropenia.  Children taking hydroxyurea for sickle cell disease often have mild neutropenia. If your child is taking hydroxyurea, the St. Jude staff will keep track of your child’s neutrophil count.

The doctor will use a measurement called the Absolute Neutrophil Count (ANC) to keep track of your child’s neutrophils. The ANC shows how well the body can fight infections, especially bacterial infections.

Platelets

Platelets are blood cells that help stop bleeding by making the blood clot. A normal platelet count is 150,000 to 400,000/mm3. If your child has a low platelet count, she may bruise or bleed more easily. Normally, sickle cell disease does not cause low platelet levels.

Keeping track of your child’s blood counts

If your child has sickle cell disease, the St. Jude staff will keep track of her blood counts. Your child will usually have a complete blood count (CBC) and reticulocyte count at each clinic visit. The doctor will tell you if your child needs more blood tests. Keeping track of your child’s blood counts is an important part of treatment. The St. Jude staff will review the test results with you and give you a copy each time your child sees the doctor. You should keep these results with your child’s medical records.

Questions?

If you have questions about your child’s blood counts or what they mean, ask the doctor or nurse. If you are outside the hospital, refer to your Important Phone Number Card. You may also call the St. Jude operator at (901) 595-3300 or toll-free 1-866-2STJUDE (1-866-278-5833) and ask for your child’s nurse case manager.

Sickle Cell Disease | Johns Hopkins Medicine

What is sickle cell disease?

Sickle cell disease is an inherited blood disorder. It is marked by flawed hemoglobin. That’s the protein in red blood cells that carries oxygen to the tissues of the body. So, sickle cell disease interferes with the delivery of oxygen to the tissues.

Red blood cells with normal hemoglobin are smooth, disk-shaped, and flexible, like doughnuts without holes. They can move through the blood vessels easily. Cells with sickle cell hemoglobin are stiff and sticky. When they lose their oxygen, they form into the shape of a sickle or crescent, like the letter C. These cells stick together and can’t easily move through the blood vessels. This can block small blood vessels and the movement of healthy, normal oxygen-carrying blood. The blockage can cause pain.

Normal red blood cells can live up to 120 days. But, sickle cells only live for about 10 to 20 days. Also, sickle cells may be destroyed by the spleen because of their shape and stiffness. The spleen helps filter the blood of infections. Sickled cells get stuck in this filter and die. With less healthy red blood cells circulating in the body, you can become chronically anemic. The sickled cells also damage the spleen. This puts you are at greater at risk for infections.

What causes sickle cell disease?

Sickle cell is an inherited disease caused by a defect in a gene.

  • A person will be born with sickle cell disease only if two genes are inherited—one from the mother and one from the father.
  • A person who inherits just one gene is healthy and said to be a “carrier” of the disease. A carrier has an increased chance of having a child with sickle cell disease if he or she has a child with another carrier. 

For parents who are each carriers of a sickle cell gene, there is a 1 in 4, or a 25 % chance of having a child with sickle cell disease.

What are the risk factors for sickle cell disease?

Having a family history of sickle cell disease increases your risk for the disease. In the United States, it mainly affects African Americans.

What are the symptoms of sickle cell disease?

The following is a list of symptoms and complications associated with sickle cell disease. However, each person may experience symptoms differently. Symptoms and complications may include:

  • Anemia. Because sickled cells are short-lived or destroyed, there are less red blood cells available in the body. This results in anemia. Severe anemia can make you feel dizzy, short of breath, and tired.
  • Pain crisis, or sickle crisis. This occurs when the flow of blood is blocked to an area because the sickled cells have become stuck in the blood vessel. The pain can occur anywhere, but most often occurs in the chest, arms, and legs. Infants and young children may have painful swelling of the fingers and toes. Interruption in blood flow may also cause tissue death.
  • Acute chest syndrome. This occurs when sickling occurs in the chest. This can be life-threatening. It often occurs suddenly, when the body is under stress from infection, fever, or dehydration. The sickled cells stick together and block the flow of oxygen in the tiny vessels in the lungs. It resembles pneumonia and can include fever, pain, and a violent cough.
  • Splenic sequestration (pooling). Crises are a result of sickle cells pooling in the spleen. This can cause a sudden drop in hemoglobin and can be life-threatening if not treated promptly. The spleen can also become enlarged and painful from the increase in blood volume. After repeated episodes,  the spleen becomes scarred, and permanently damaged. Most children, by age 8, do not have a working spleen either from surgical removal, or from repeated episodes of splenic sequestration. The risk of infection is a major concern of children without a working spleen. Infection is the major cause of death in children younger than age 5 in this population.
  • Stroke. This is another sudden and severe complication of people with sickle cell disease. The misshapen cells can block the major blood vessels that supply the brain with oxygen. Any interruption in the flow of blood and oxygen to the brain can result in severe brain damage. If you have one stroke from sickle cell anemia, you are more likely to have a second and third stroke.
  • Jaundice, or yellowing of the skin, eyes, and mouth. Jaundice is a common sign and symptom of sickle disease. Sickle cells do not live as long as normal red blood cells and, therefore, they are dying faster than the liver can filter them out. Bilirubin (which causes the yellow color) from these broken down cells builds up in the system causing jaundice.
  • Priapism.  This is a painful obstruction of the blood vessels in the penis by sickle cells. If not promptly treated, it can result in impotence.

The symptoms of sickle cell disease may look like other blood disorders or medical problems. Always consult your health care provider for a diagnosis.

How is sickle cell disease diagnosed?

Along with a complete medical history and physical exam, you may have blood and other tests.

Many states routinely screen newborns for sickle cell so that treatment can begin as soon as possible. Early diagnosis and treatment can reduce the risk of complications.

Hemoglobin electrophoresis is a blood test that can determine if a person is a carrier of sickle cell, or has any of the diseases associated with the sickle cell gene.

How is sickle cell disease treated?

Your doctor will consider your age, overall health and other factors when determining the best treatment for you.

Early diagnosis and prevention of complications is critical in sickle cell disease treatment. Treatment aims to prevent organ damage including strokes, prevent infection, and treat symptoms. Treatment may include:

  • Pain medications. This is for sickle cell crises.
  • Drinking plenty of water daily (8 to 10 glasses). This is to prevent and treat pain crises. In some situations, intravenous fluids may be required.  
  • Blood transfusions. These may help treat anemia and prevent stroke. They are also used to dilute the sickled hemoglobin with normal hemoglobin to treat chronic pain, acute chest syndrome, splenic sequestration, and other emergencies.
  • Vaccinations and antibiotics. These are used to prevent infections.
  • Folic acid. Folic acid will help prevent severe anemia.
  • Hydroxyurea. This medication helps reduce the frequency of pain crises and acute chest syndrome. It may also help decrease the need for blood transfusions. The long-term effects of the medication are unknown.
  • Regular eye exams. These are done to screen for retinopathy.  
  • Bone marrow transplant. Bone marrow transplants can cure some people with sickle cell disease. The decision to have this procedure is based on the severity of the disease and ability to find a suitable bone marrow donor. These decisions need to be discussed with your doctor and are only done at specialized medical centers.

What are the complications of sickle cell disease?

Any and all major organs are affected by sickle cell disease. The liver, heart, kidneys, gallbladder, eyes, bones, and joints can suffer damage from the abnormal function of the sickle cells and their inability to flow through the small blood vessels correctly. Problems may include the following:

  • Increased infections
  • Leg ulcers
  • Bone damage
  • Early gallstones
  • Kidney damage and loss of body water in the urine
  • Eye damage
  • Multiple organ failure

Living with sickle cell disease

Sickle cell disease is a life-long condition. Although the complications of sickle cell disease may not be able to be prevented entirely, living a healthy life-style can reduce some of the complications.

It is important to eat a healthy diet with lots of fruits, vegetables, whole grains, and protein, and drink lots of fluids.

Do not take decongestants because they cause constriction of blood vessels and could trigger a crisis.

Other factors that may trigger a crisis include high altitudes, cold weather, swimming in cold water, and heavy physical labor.

Avoid infections by getting an annual flu shot, washing your hands frequently, avoiding those who are sick, and getting regular dental exams.

Key points

  • Sickle cell disease is an inherited blood disorder marked by defective hemoglobin.
  • It inhibits the ability of hemoglobin in red blood cells to carry oxygen.
  • Sickle cells tend to stick together, blocking small blood vessels causing painful and damaging complications.
  • Sickle cell disease is treated with pain medications as needed, drinking 8 to 10 glasses of water each day, blood transfusions, and medications.

Next steps

Tips to help you get the most from a visit to your health care provider:

  • Before your visit, write down questions you want answered.
  • Bring someone with you to help you ask questions and remember what your provider tells you.
  • At the visit, write down the names of new medicines, treatments, or tests, and any new instructions your provider gives you.
  • If you have a follow-up appointment, write down the date, time, and purpose for that visit.
  • Know how you can contact your provider if you have questions.

Sickle Cell Anemia: Symptoms, Causes, Treatments



Overview

What is sickle cell anemia?

Sickle cell anemia is a blood disease that affects red blood cells. Normal red blood cells are round. In people with sickle cell anemia, hemoglobin – a substance in red blood cells – becomes defective and causes the red blood cells to change shape. The faulty hemoglobin is called hemoglobin S (HgbS), and it replaces normal hemoglobin which is called hemoglobin A (HgbA). Over time, the red blood cells become rigid and shaped like crescent moons or sickles.

The sickle-shaped red blood cells:

  • Clog blood vessels, causing episodes of pain and cutting off oxygen to tissues and organs.
  • Get trapped in the spleen (an organ that gets rid of old cells) where they are destroyed. The body cannot replace the lost cells fast enough. As a result, the body has too few red blood cells, a condition known as anemia.

Sickle cell anemia is a serious disease that can require frequent hospital stays. Children and young adults can die from the disease.

Who gets sickle cell anemia?

In the United States, the disease occurs most often among African Americans (in about 1 of every 400 African American births) and among Hispanics of Caribbean ancestry (1 in every 1,000 to 1,400 Hispanic American children). Throughout the world, the disease is also found among people of Arabian, Greek, Italian, Sardinian, Turkish, Maltese, and southern Asian ancestry.

Is there a difference between sickle cell anemia and sickle cell trait?

Yes. A person can have a mixture of normal and faulty hemoglobin in their red blood cells without having sickle cell disease. This condition is called “sickle cell trait.” People with sickle cell trait have enough normal hemoglobin in their red blood cells to prevent the cells from sickling. One in 12 African Americans in the United States has sickle cell trait.

It’s important to remember that people with sickle cell trait do not have sickle cell disease. They also usually do not develop sickle cell disease, except in unusual circumstances. However, people with sickle cell trait can genetically pass the trait to their children. If two people with sickle cell trait have children together, there is a 1 in 4 chance that their children will have sickle cell anemia.

What are the chances that my child will be born with sickle cell anemia or sickle cell trait?

If you and your partner both have sickle cell trait, your child has a 25% chance of being born with sickle cell anemia. If only one of you has sickle cell trait, your child cannot be born with sickle cell anemia, but there is a 50% chance that your child will be born with sickle cell trait.

If one parent has sickle cell disease and one parent has sickle cell trait, there is a 50% chance that their children will be born with sickle cell disease.



Symptoms and Causes

How does a person get sickle cell anemia?

People with sickle cell anemia inherit the disease, which means that the disease is passed on to them by their parents as part of their genetic makeup. Parents cannot give sickle cell anemia to their children unless they both have the faulty hemoglobin in their red blood cells.

What are the symptoms and complications of sickle cell anemia?

  • Periods of pain that can last a few hours to a few days.
  • Blood clots.
  • Swelling in hands and feet.
  • Joint pain that resembles arthritis.
  • Chronic neuropathic pain (nerve pain).
  • Life-threatening infections.
  • Anemia (decrease in red blood cells).



Diagnosis and Tests

How can I know if I have sickle cell trait?

Your healthcare provider can perform a special blood test to tell if you have sickle cell anemia or sickle cell trait. You may decide to have this test before you plan to have children.

In many states, the law requires newborn babies to be tested for sickle cell disease, regardless of their ethnic background. The testing is done right away so that children born with sickle cell disease can receive treatment to protect them against life-threatening infections. These children need to be followed very closely by a healthcare provider.



Management and Treatment

Can sickle cell anemia be cured?

No. As of today, there’s no cure for sickle cell anemia. However, there are treatments that have reduced the death rate among children and the levels of pain caused by the disease.

If your baby has sickle cell anemia, your healthcare provider will explain what you can do to help your child live a normal life. Your baby may need to take medicine by the mouth for up to 10 years to prevent life-threatening infections. Later in life, care focuses more on managing pain.



Living With

How can I manage my pain if I have sickle cell anemia?

Acute pain can occur during a vaso-occlusive crisis (VOC). This happens when the sickle-shaped blood cells block the flow of blood in small vessels. The VOC can lead to tissue damage and pain. This type of pain should be treated as a medical emergency.

Some patients develop chronic pain, which is pain that lasts for more than 3 to 6 months. The exact mechanism that causes chronic pain in some patients and not others is not known. The treatment of the chronic pain should be tailored to the specific type of pain that is being experienced. Wokring with a pain management doctor can help you manage your pain by applying different methods. The goal is to use the least of amount of medication and gain the greatest amount of function.

How Does Sickle Cell Cause Disease?

How Does Sickle Cell Cause Disease?
last revised April 11, 2002



How Does Sickle Cell Cause Disease?



The Mutation in Hemoglobin



Sickle
cell disease is a blood condition seen most commonly in people of African
ancestry and in the tribal peoples of India.
Clinically significant sickle cell syndromes also occur in people of Mediterranean
and Middle Eastern background. Here, the most common problem is a combination
sickle cell and beta thalassemia genes. The sickle cell mutation reflects
a single change in the amino acid building blocks of the oxygen-transport
protein, hemoglobin. This protein, which is the component that gives red
cells their color, has two subunits. The alpha subunit is normal in people
with sickle cell disease. The beta subunit has the amino acid valine at
position 6 instead of the glutamic acid that is normally present. The alteration
is the basis of all the problems that occur in people with sickle cell
disease. The schematic diagram shows the first eight of the 146 amino acids
in the beta globin subunit of the hemoglobin molecule. The amino acids
of the hemoglobin protein are represented as a series of linked, colored
boxes. The lavender box represents the normal glutamic acid at position
6. The dark green box represents the valine in sickle cell hemoglobin.
The other amino acids in sickle and normal hemoglobin are identical.

Schematic Represntation of the Amino Acid Substitution in Sickle Cell Disease
Figure 1. The chain of colored boxes represent the first eight amino acids in the beta chain of hemoglobin. The sixth position in the normal beta chain has glutamic acid, while sickle beta chain has valine. This is the sole difference between the two.

 The molecule, DNA (deoxyribonucleic acid), is the fundamental
genetic material that determines the arrangement of the amino acid building
blocks in all proteins. Segments of DNA that code for particular proteins
are called genes. The gene that controls the production of the beta globin
subunit of hemoglobin is located on one of the 46 human chromosomes (chromosome
#11). People have twenty-two identical chromosome pairs (the twenty-third
pair is the unlike X and Y chromosomes that determine a person’s sex).
One of each pair is inherited from the father, and one from the mother.
Occasionally, a gene is altered in the exchange between parent and offspring.
This event, called mutation, occurs extremely rarely. Therefore, the inheritance
of sickle cell disease depends totally on the genes of the parents.

  If only one of the beta globin genes is the “sickle” gene and
the other is normal, the person is a carrier for sickle cell disease. The
condition is called sickle
cell trait. With a few rare exceptions, people with sickle cell trait
are completely normal. If both beta globin genes code for the sickle protein,
the person has sickle cell disease. Sickle cell disease is determined at
conception, when a person acquires his/her genes from the parents. Sickle
cell disease cannot be caught, acquired, or otherwise transmitted.

Also, sickle cell trait does not develop into sickle cell disease. Sickle cell trait
partially protects people from the deadly consequences of malaria. The frequency
of the sickle cell gene reached high levels in Africa and India due to the protection
against malaria that occurred for people with sickle cell trait.

Oxygen and the Formation of Polymers of Sickle Hemoglobin

Figure 2. Normal hemglobin exists as solitary units whether
oxygenated or deoxygenated (upper panel). In contrast, sickle hemoglobin molecules
adhere when they are deoxygenated, forming sickle hemoglobin polymers (lower panel).

  The hemoglobin molecule (made of alpha and beta globin subunits)
picks up oxygen in the lungs and releases it when the red cells reach peripheral
tissues, such as the muscles. Ordinarily, the hemoglobin molecules exist
as single, isolated units in the red cell, whether they have oxygen bound
or not. Normal red cells maintain a basic disc shape, whether they are
transporting oxygen or not.

The
picture is different with sickle hemoglobin (Figure 2). Sickle hemoglobin exists as
isolated units in the red cells when they have oxygen bound. When sickle
hemoglobin releases oxygen in the peripheral tissues, however, the molecules
tend to stick together and form long chains or polymers. These rigid polymers
distort the cell and cause it to bend out of shape. While most distorted
cells are simply shaped irregularly, a few have a cresent-like appearence
under the microscope. These cresent-like or “sickle shaped” red cells gave
the disorder its name. When the red cells return to the lungs and pick
up oxygen again, the hemoglobin molecules resume their solitary existence
(the left of the diagram).

   A single red cell may traverse the circulation four times
in one minute. Sickle hemoglobin undergoes repeated episodes of polymerization
and depolymerization. This cyclic alteration in the state of the molecules
damages the hemoglobin and ultimately the red cell itself.

 Polymerized sickle hemoglobin does not form single strands. Instead,
the molecules group in long bundles of 14 strands each that twist in a
regular fashion, much like a braid (Figure 3).

Schematic Representaion of Polymerized Sickle Hemoglobin

Figure 3. Polymers of deoxygenated sickle hemoglobin molecules. Each hemoglobin
molecule is represented as a sphere. The spheres twist in an alpha helical bundle
made of 14 sickle hemoglobin chains.


These bundles self-associate into even larger structures that stretch and
distort the cell. An analogy would be a water balloon which was stretched
and deformed by icicles. The stretching of the balloon’s rubber is
similar to what happens to the membrane of the red cell. Polymers tend
to grow from a single start site (called a nucleation site) and often grow
in multiple directions. Star-shaped clusters of hemoglobin S polmers develop
commonly.

  Despite their imposing appearance, the sickle hemoglobin polymers
are held together by very weak forces. The abnormal valine amino acid at
position 6 in the beta globin chain interacts weakly with the beta globin
chain in an adjacent sickle hemoglobin molecule. The complex twisting,
14-strand structure of the bundles produces multiple interactions and cross-interactions
between molecules. The weak nature of the interaction opens one strategy
to treat sickle cell disease.

   Some types of hemoglobin molecules, such as that found
before birth (fetal hemoglobin),
block the interactions between the deoxygenated hemoglobin S molecules.
All people have fetal hemoglobin in their circulation before birth. Fetal
hemoglobin protects the unborn child and newborns from the effects of sickle
cell hemoglobin. Unfortunately, this hemoglobin disappears within the first
year after birth. One approach to treating sickle cell disease is to rekindle
production of fetal hemoglobin. The drug, hydroxyurea
induces fetal hemoglobin production in some patients with sickle cell disease
and improves the clinical condition
of some people.



The Sickle Red Cell

Capillary Flow of Normal and Sickle Red Cells

Figure 4. Normal red cells maintain their shape as they pass through the capillaries
and release oxygen to the peripheral tissues (upper panel). Hemoglobin polymers form
in the sickle rell cells with oxygen release, causing them to deform. The deformed
cells block the flow of cells and interrupt the delivery of oxygen to the tissues
(lower panel).


Figure 4 shows the changes that occur as sickle or normal red
cells release oxygen in the microcirculation. The upper panel shows that
normal red cells retain their biconcave shape and move through the smallest
vessels (capillaries) without problem. In contrast, the hemoglobin polymerizes
in sickle red cells when they release oxygen, as shown in the lower panel.
The polymerization of hemoglobin deforms the red cells. The problem, however,
is not simply one of abnormal shape. The membranes of the cells are rigid
due in part to repeated episodes of hemoglobin polymerization/depolymerization
as the cells pick up and release oxygen in the circulation. These rigid
cells fail to move through the small blood vessels, blocking local blood
flow to a microscopic region of tissue. Amplified many times, these episodes
produce tissue hypoxia (low oxygen supply). The result is pain, and often
damage to organs.

 The damage to red cell membranes promotes many of the complications
of sickle cell disease. Robert Hebbel at the University of Minnesota and
colleagues were among the first workers to show that the heme
component of hemoglobin tends to be released from the protein with repeated
episodes of sickle hemoglobin polymerization. Some of this free heme lodges
in the red cell membrane. The iron in the center of the heme molecule promotes
formation of very dangerous compounds, called reactive oxygen species.
These molecules damage both the lipid and protein components of the red
cell membrane. Membrane stiffness is one of the consequences of this injury.
Also, the damaged proteins tend to clump together to form abnormal clusters
in the red cell membrane. Antibodies develop to these protein clusters,
leading to even more red cell destruction (hemolysis).

  The anemia in sickle cell disease is caused by red cell destruction,
or hemolysis. The production of red cells by the bone marrow increases
dramatically, but is unable to keep pace with the destruction. Red cell
production increases by five to ten-fold in most patients with sickle cell
disease. The average half-life of normal red cells is about 40 days. In
patients with sickle cell disease, this value can fall to as low as four
days. The volume of “active” bone marrow is much greater than normal in
patients with sickle cell disease due to the demand for greater red cell
production.

The degree of anemia varies widely between patients. In general,
patients with sickle cell disease have hematocrits that are roughly half
the normal value (e.g., about 25% compared to about 40-45% normally).
Patients with hemoglobin SC disease (where one of the beta globin genes
codes for hemoglobin S and the other for the variant, hemoglobin C) have
higher hematocrits than do those with homozygous Hb SS disease. The hematocrits
of patients with Hb SC disease run in low- to mid-thirties. The hematocrit
is normal for people with sickle cell trait.

 

 


New Views of Sickle Cell Disease Pathophysiology and Treatment | Hematology, ASH Education Program

*

Life Sciences Division, Lawrence Berkeley Laboratory, 1 Cyclotron Road, Bldg. 74-157, Berkeley CA 94720

An important pathophysiologic feature of sickle cell disease is episodic occurrence of vasoocclusive events that precipitate acute painful episodes. Vasoocclusion of small and sometimes large vessels is the hallmark of sickle cell disease, accounting for much of its morbidity and mortality. Decades of research on sickle hemoglobin polymerization have culminated in elegant elucidations of the contributions of polymerization-dependent processes to various pathophysiologic manifestations of the sickle cell disease. However, it is reasonable to surmise that hemoglobin polymerization in and of itself is not sufficient to account for the episodic nature of vascular occlusion.

Based upon studies from a number of laboratories, there is emerging consensus that a key contributor to vasoocclusion may be the increased tendency of sickle red cells to adhere to vascular endothelium.1,2  Vasoocclusion can occur when transit time of red cells through the capillaries is longer than the delay time for deoxygenation-induced hemoglobin polymerization of sickle hemoglobin. As adherence of sickle red cells to vascular endothelium will impede blood flow and thereby increase capillary transit time, it has been suggested that increased cell adherence can initiate and propagate vasoocclusion.

Factors such as inflammatory mediators that activate endothelial cells and thereby enhance endothelial adhesivity of sickle red cells thus have the potential to trigger vasoocclusive episodes. A partial list of agonists that may alter endothelium and play a role in sickle cell disease includes TNF-α, interferon-γ, IL-1β, vascular endothelial growth factor (VEGF), thrombin, and histamine, and the effects of hypoxia and reperfusion.

Seminal studies by Hebbel two decades ago demonstrated that sickle red cells exhibit increased adherence to endothelial cells in vitro and that the extent of in vitro sickle cell adhesivity correlated with vasoocclusive severity. Mohandas and Evans showed that both red cell membrane changes and plasma factors account for increased sickle cell adherence to endothelial cells in vitro. Subsequently, a number of studies have defined adhesion pathways involved in sickle cell adherence to cultured endothelial cells under static and flow conditions.5,6,7,8,9,10  Adhesive ligands identified on sickle red cells include CD36, α4β1 integrin, sulfated glycolipid and the Lutheran blood group antigen. On the endothelial side, cytokine-induced VCAM-1, a ligand for α4β1, and αvβ3 integrin that binds von Willebrand factor (vWf) and thrombospondin (TSP) have been shown to mediate sickle cell adherence. Other potential adhesive receptors on endothelial cells include GPIb and CD36. The adhesive proteins in plasma, TSP released by platelets, and vWF released by endothelial cells mediate adhesion by serving as bridging molecules between adhesive receptors on red cells and endothelial cells. Sickle red cell interaction with the vessel wall may also involve interaction with subendothelial matrix components such as laminin, TSP, vWf or fibronectin exposed by vascular injury. The Lutheran blood group antigen has been shown to be a major laminin receptor on red cells, while a sulfated glycolipid has been shown to bind to laminin and to TSP. Based on data from these extensive series of in vitro studies it is reasonable to conclude that sickle red cells indeed exhibit an increased adhesive phenotype and that a large number of cell adhesion receptors, plasma proteins and subendothelial matrix components are involved in mediating adhesive interactions.

The critical question that has not yet been adequately addressed is the extent to which the in vitro documented adhesive phenotype of sickle red cells contributes to vasoocclusion in vivo. While there are no easy experimental strategies to address these problems, some progress is being made through physiological studies using animal models. Intravital microscopy has been employed to study sickle red cell interaction with vessel wall using rat mesocecum ex vivo perfused with human sickle cells and in transgenic mice that express high levels of human sickle hemoglobin.11,12,13  The ex vivo rat studies showed that deformable low-density sickle red cells are more likely to adhere than undeformable dense sickle cells and that adhesion was limited to postcapillary venules. A recent study using the same ex vivo rat model has convincingly demonstrated that treatment with the αvβ3-blocking antibody largely abolished platelet-activating factor-stimulated sickle red cell adhesion to vessel wall.14  These types of in vivo studies are beginning to provide support to the thesis that increased sickle cell adherence could have significant effects on flow dynamics in the microvasculature and that anti-adhesive therapy may have clinical benefits.

There are, however, a number of significant issues regarding the in vivo role of sickle cell adherence that cannot be addressed using ex vivo animal models. A major hurdle for progress has been the lack of a suitable animal model for sickle cell disease. The recent development of transgenic/knockout sickle mice that express exclusively human sickle hemoglobin and exhibit many clinical features of human disease15  is likely to prove to be a valuable tool to begin to critically evaluate the role of cell adherence in vasoocclusion and the potential clinical benefit of anti-adhesive therapeutic strategies. While much work still remains to be done, with the recent exciting breakthroughs in our understanding of cell adhesion it is likely that anti-adhesion therapies may become viable treatment options for management of vasoocclusive crisis during the coming decade.

Hematocrit among Blacks with Sickle Cell Trait on JSTOR

Abstract

Hematocrit levels were studied in 8,581 male and 10,618 female Blacks aged 0-59 years, in Upstate New York. Persons with sickle-cell trait and with normal hemoglobin were compared. Differences in mean levels were small and not statistically significant, except for males aged 12-13 and females aged 8-9. Lower means for trait persons at these ages could be a chance finding, or could possibly reflect delayed physical maturation. Criteria of “low” and “high” hematocrit were selected somewhat arbitrarily, from previously reported standards based on population distributions. The frequency of “low” hematocrit did not differ between trait and normal groups in any age-sex category. Adult males (aged 17-59), but not females, with the trait were less likely to have a “high” hematocrit compared with normal males. These findings suggest the need for more detailed analysis on other large populations.

Journal Information

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Gene therapy of sickle cell anemia in adolescents using lentiviral vector

In article New England Journal of Medicine dated March 2
2017 published a clinical case about the successful treatment of a patient with a severe form
sickle cell anemia (SCA) through gene therapy.

Sickle cell anemia is one of the most common hereditary monogenic
diseases.About 90,000 people in the United States have sickle cell disease and
worldwide, more than 275,000 babies are born with the disease every year.

SKA is a disease based on a change in the shape of erythrocytes, due to
the appearance of pathological hemoglobin S (HbS), as a result of a point mutation in the β-chain gene
hemoglobin

Clinical manifestations are vaso-occlusive crises in vital organs.What is the bottom line
leads to irreversible organ damage, poor quality of life, reduction
life expectancy and even death.

The main method of treatment is the use of a hydroxyurea preparation, the mechanism of action
which is to increase the level of fetal hemoglobin. Many patients use
hydroxyurea, is the only treatment that relieves the manifestations of the disease.

Allogeneic transplantation is currently the only therapy for patients with
severe form of SKA. However, less than 18% of patients have fully compatible
sibling donor.

The use of gene therapy in patients with SCD may provide long-term clinical
remission.

Previously, there were reports of effective treatment of SCA in mice, through gene therapy with
using a viral vector.In this article, the results of a successful
treating a patient who received gene therapy in clinical study HGB-205.

Clinical case :

Boy, 13 years old

Diagnosis: severe form of SCA, with the βS / βS genotype (point deletion of the gene 3.7 kb
α-globin)

Clinical manifestations: numerous vaso-occlusive crises, episodes of angina pectoris,
bilateral osteonecrosis of the hip joints.

Operations: cholecystectomy and splenectomy.

Treatment: from 2 to 9 years received hydroxyurea therapy, clinical symptoms remained
the old ones. Since 2010, the boy has been treated with chelated iron at a dose of 17 mg / kg in
day.

In October 2014, gene therapy was applied using a lentiviral vector.

Lentiviral vector encoding human βA-globin gene, similar to gamma globin,
subunit of fetal hemoglobin, quenches HbS polymerization.

The patient underwent myeloablative conditioning with busulfan.

After a 2-day break, reinfusion of autologous transduced CD34 + cells (5.6
× 106 / kg MT CD34 +).

Substitution blood transfusions were continued until the HbA content was 25 to 30% of
total hemoglobin.

Basic laboratory parameters before gene therapy (at screening) and at 3-month intervals
after transfusion of transduced autologous CD34 + cells

Standard

Screening *

3 months.*

6 months

9 months

12 months

15 months

Hemoglobin g / dL

13.0-18.0

10.1

12.0

10.6

11.4

11.7

11.8

Erythrocytes in mm3

4.5 – 6.2 million

3.7 million

3.9 million

3.7 million

4 million

4.2 million

4.3 million

Reticulocytes in mm3

20 – 80 thousand

238 thousand

259 thousand

132 thousand

131 thousand

143 thousand

143 thousand

MCH pg

25-30

28

31

29

28

28

28

MCHC g / dl

31-34

35

34

35

36

35

35

Platelets in mm3

150-450 thousand

356 thousand

52 thousand

122 thousand

157 thousand

168 thousand

201 thousand

Neutrophiles in mm3

1.5-7.0 K

4.2 thousand

2.4 thousand

3.1 thousand

2.5 thousand

3.0 thousand

2.2 thousand

Total bilirubin μmol / L

0-17

50

15

20

14

12

12

LDH IU / L

125-243

626

285

254

226

274

212

CRP ng / ml

<500

191

814

129

135

158

Ferritin μg / L

22-275

265

869

1095

520

363

Transferrin g / L

1.9-3.2

1.4

1.6

1.7

1.5

1.7

Transferrin saturations %

16-35

72

35

56

40

Serum transferrin receptor mg / L

0.8-1.7

5.7

3.0

2.3

2.6

2.5

Iron μmol / L

12-30

26

18

14

20

17

Hepcidin ng / ml

1-20

12.9

19.9

ALT IU / L

5-45

22

76

125

116

53

41

AST ME / L

5-40

53

57

71

50

49

35

* replacement transfusions were performed prior to initiation of gene therapy, and maintenance transfusions were
erythrocytes were completely discontinued 88 days after transplantation.

At the moment, the patient is in complete clinical remission, with full compensation of hemolysis and
lack of clinical manifestations of the disease.

The advantage of this approach is the reduced risk of bone marrow rejection compared to
allogeneic transplantation, and there is no need to search for a donor.

“Complete clinical remission can be achieved with this treatment,” said
Steven J.Gray, PhD, from the Gene Therapy Center at the University of North Carolina, Chapel
Hill, for Medscape Medical News.

“Sickle cell anemia, one of the classic genetic diseases, about which
everyone learns in their freshman year of biology. For those who work in the field of gene therapy, everyone
day, this is a real chance to achieve a complete cure for sickle cell anemia. And it gives
hope that the next generation of students will read about this incurable disease
only in history books, ”added Steven J.Gray.

Sources :

  1. http://www.nejm.org/doi/full/10.1056/NEJMoa1609677
  2. Brousseau DC, Panepinto JA, Nimmer M, Hoffmann RG. The number of people with sickle-cell
    disease in the United States: national and state estimates. Am J Hematol 2010; 85: 77-8.
  3. Modell B, Darlison M.Global epide- miology of haemoglobin disorders and derived service
    indicators. Bull World Health Organ 2008; 86: 480-7.
  4. Ingram VM. A specific chemical dif- ference between the globins of normal human and
    sickle-cell anaemia haemo-globin. Nature 1956; 178: 792-4.
  5. Strouse JJ, Lanzkron S, Beach MC, et al. Hydroxyurea for sickle cell disease: a systematic
    review for efficacy and toxicity in children.Pediatrics 2008; 122: 1332-42.
  6. Bernaudin F, Socie G, Kuentz M, et al. Long-term results of related myeloabla- tive
    stem-cell transplantation to cure sickle cell disease. Blood 2007; 110: 2749-56.
  7. Bhatia M, Walters MC. Hematopoietic cell transplantation for thalassemia and sickle cell
    disease: past, present and future. Bone Marrow Transplant 2008; 41: 109-17.
  8. Krishnamurti L, Abel S, Maiers M, Flesch S. Availability of unrelated donors for
    hematopoietic stem cell transplantation for hemoglobinopathies. Bone Mar- row Transplant
    2003; 31: 547-50.
  9. Mentzer WC, Heller S, Pearle PR, Hackney E, Vichinsky E. Availability of related donors for
    bone marrow trans- plantation in sickle cell anemia.Am J Pediatr Hematol Oncol
    1994; 16: 27-9.

Material prepared : Subora Anton Yurievich, hematologist of the Department of Oncology,
hematology and bone marrow transplantation with intensive care unit, and clinical resident Oleinik
Yu.A.

Sickle cell anemia “Lakhta Clinic” Lakhta Clinic

Terminology

For more details about the composition and biological role of blood, about the essence of anemia – see.material “Anemia. Blood and bloodlessness. ”

Sickle cell anemia is a severe hereditary disease, also known as drepanocytosis, meniscocytosis, S-hemoglobin disease, Herrick’s syndrome, African hemolytic anemia (hemolytic – Greek literal “dissolving, decomposing blood”). Modern history The study of this type of anemia began, as it is believed, in the middle of the 19th century , when the spleen was not found in the body of an African slave executed for escape during an autopsy.Then in 1910 a message appeared, sponsored by Professor of Cardiology James B. Herrick and his intern Ernest E. Irons . In a blood test of a 20-year-old student who, since 1904, had been treated for “anemia, muscular rheumatism and bile spillage” (he died of pneumonia in 1916) Ironz observed and for the first time described erythrocytes of a strange shape, which he defined as “elongated and sickle. ” The name “sickle cell anemia” was first used as a diagnosis by Verne Mason in 1922 . Since the 1930s, epidemiological studies of this disease have begun in samples of children of African descent.

It can be assumed that the genetic mutation leading to sickle cell anemia appeared on the African continent – and, oddly enough, was fixed in the population as a useful trait: carriers of the gene and patients with this form of anemia show relative resistance to malaria. Plasmodium malaria parasitizes and destroys red blood cells, but erythrocytes, genetically mutilated and carrying a completely different hemoglobin (see.below), for Plasmodium “inedible”. And although the anemia of malaria is not sweeter, the mortality rate of swamp fever is still higher: those who had at least some immunity survived.

In an actively migrating humanity, which is becoming more and more international and gradually interracial, sickle cell anemia is widespread. However, a certain endemicity persists today: in Equatorial Africa, the Mediterranean Basin, India, and the Middle East, the frequency of genetic carriage (not to be confused with clinical morbidity) reaches 40%.
According to a special study conducted in 2001 in Jamaica, the average life expectancy of patients with homozygous sickle cell disease is 53 years for men and 58 years for women. About 90% live to 20 years old, about half to 50 years.

In other words, the problem is very serious, it is characterized by high medical and social significance and needs effective solutions, which are currently being searched for by leading specialized research centers.The prevalence of hereditary hemoglobinopathies (including sickle cell anemia) in the world is estimated at 3-7%. In the early 2010s, WHO classified sickle cell anemia as a global health problem.

The epidemiological situation and mortality rates in third world countries are unknown or insufficiently reliable.

According to the literature data, due to migration processes, the incidence in Russia shows a significant and stable tendency to increase, especially in Moscow and St. Petersburg.

Reasons

S-hemoglobin (from the English “a sickle” – sickle), encoded by a faulty gene, is much more viscous and about a hundred times less soluble than normal A-hemoglobin; in addition, the ability to bind oxygen and transport it to tissues is many times lower, which is what causes the anemic symptomatology of hypoxia itself. Erythrocytes containing altered hemoglobin differ in the shape of an elongated deformed crescent or sickle from normal blood cells, which have the appearance of a relatively thick biconcave disc.The unnatural shape and stiffness of S-erythrocytes leads to a tendency for them to block capillary channels. Hemolysis is sharply accelerated, i.e. the lifespan of S ‑ erythrocytes is much shorter than that of normal red cells.

In the patient’s blood, both normal and abnormal erythrocytes, or only abnormal ones, may be present. Obviously, in the second case, the disease is much more severe and the prognosis is worse; the first option may be little or even asymptomatic.
The type of inheritance is autosomal recessive.This means that for two parents – carriers of the gene, the probability of having a child with the same gene is 50%, and with the clinical form of sickle cell anemia – 25%. If only one of the parents is the carrier, the probability of inheriting the gene remains fifty percent, but the disease itself does not manifest in the child.

Symptoms

Like most genetic diseases, sickle cell disease is characterized by an extraordinary variety of possible symptoms, syndromes and complications.Their variability is so great that no clinical picture and no individual case can be considered typical.

The debut in most cases occurs in early childhood, and then three periods can be traced in the development of the disease.

In the initial period , as a rule, the symptoms of microthrombosis, osteoarticular pains and pains of other localization, swelling of the joints, enlargement of the spleen, and yellowness (due to the accelerated breakdown of hemoglobin) dominate.Such children are highly prone to infections, including osteomyelitis. The course of the disease at this stage is often of a crisis nature and is easily aggravated under any unfavorable conditions. For example, a hemolytic-type crisis is often provoked by an infection and can be fatal; aplastic, sequestration, vascular (thrombotic) crises are also life-threatening syndromes.
In many cases, there is a characteristic deformation of the structures of the musculoskeletal system and the bones of the skull: kyphosis, lordosis, acrocephaly (“tower skull”), as well as serious delays in psychophysical development.

At the second stage , abnormally intense production of erythrocytes can be observed as compensation for their failure. Due to thrombosis, heart or renal failure, strokes, diabetes mellitus, cirrhosis of the liver, trophic ulcers of the legs often develop. Most patients with such a severe picture of the second period die within several years.

The third period, if it occurs at all, is characterized by moderate hemolytic symptoms.The absence of the spleen (see above) is due to the phenomenon of wrinkling and self-destruction (autosplenectomy) after repeated heart attacks. The liver remains enlarged, there is a high predisposition to the purulent-inflammatory course of any infectious diseases.

Optional (possible in different cases, but not mandatory) complications of sickle cell anemia are cholelithiasis, aseptic necrosis of bone tissue (avascular osteonecrosis), immunodeficiency, priapism in men, preeclampsia and miscarriages in pregnant women, intrauterine growth retardation, necrosis, retinopathy (retinal detachment can result in complete blindness), pulmonary hypertension, and many others.dr.

More or less prolonged attacks of acute pain in bones, joints and muscles are characteristic. The National Health Service of Great Britain has included sickle cell anemia in the list of the most painful conditions.

Diagnostics

The diagnosis is established by the characteristic combination of symptoms common for anemias and specific manifestations. A thorough multifactorial laboratory blood test is being performed .A medical genetic examination is prescribed.

Treatment

Today there are only palliative, symptomatic treatment , which in many cases requires the participation of several specialized specialists. Prevention of infectious diseases, good nutrition, control of adequate intake of vitamins (especially B9 and B12) are of great importance.

It should be noted that in March 2017 The New England Journal of Medicine published an article in which a large group of authors reported the first case of significant relief of sickle cell anemia by genetic engineering.A French teenager received this treatment at the Necker University Hospital (Paris), known since 1802 as the world’s first specialized medical facility for children.

However, the prognosis of the further development and course of the disease, as well as the prospects for introducing the method into clinical practice, are still unclear. Hopefully, this success is definitely outstanding! – will mark the long-awaited and much-needed revolution in the treatment of sickle cell anemia and, in general, chromosomal diseases.

90,000 Blood transfusion policy for sickle cell disease during pregnancy

What is the problem?

Sickle cell anemia is an inherited disorder of the structure of hemoglobin, a protein in red blood cells that carries oxygen. In this condition, abnormal hemoglobin S from one parent is combined with another abnormal hemoglobin from the other parent. Hemoglobin S inherited from both parents (HbSS genotype), characterized as sickle cell disease, is the most common form.

Why is it important?

When the partial pressure of oxygen is low, hemoglobin S crystallizes and the red blood cells become sickle-shaped. Sickle reduces the ability of red blood cells to move through small blood vessels, causing vascular blockage and early destruction of red blood cells. Breakdown of red blood cells and massive accumulation of damaged red blood cells in the liver and spleen cause anemia. Acute illnesses include painful crises, pulmonary embolism, acute chest syndrome, and congestive heart failure.Therefore, a pregnant woman with sickle cell disease should be closely monitored.

Depending on the policy of the healthcare organization, blood transfusions can be given to a pregnant woman with HbSS at regular intervals with relatively few or no symptoms to improve the ability of cells to carry oxygen by increasing the concentration of hemoglobin in the blood and decreasing the level of hemoglobin S; or only with the development of medical complications or complications of pregnancy.Frequent blood transfusion carries the risk of developing blood-borne infections and excess iron levels.

This review aims to determine if there is a difference between blood transfusion at regular intervals before serious complications and medically indicated blood transfusion, and whether these methods have different effects on maternal and child health.

What evidence have we found?

We searched for evidence as of May 30, 2016 and found one clinical trial with an unclear risk of bias in which 72 women with sickle cell disease (hemoglobin SS) before 28 weeks of gestation were randomized (randomly assigned) to one of two groups with different strategies of blood transfusion.The clinical trial found no differences in severe illness and mortality among mothers or newborns. There was also no difference in the risk of a delayed response to a blood transfusion. This clinical trial suggests that blood transfusion at frequent intervals reduces the risk of a painful crisis with a high degree of uncertainty about the size of the effect, compared to transfusion only when medically indicated. Blood transfusion was performed in a ratio of 4: 1 as prophylactic versus selective, respectively.Overall, the quality of the evidence for outcomes meaningful to women is very low.

What does this mean?

The available evidence is insufficient to support changes in clinical practice and policy. More research is needed.

How sickle blood cells adhere to blood vessels

One of the most common complications of sickle cell disease is that deformed red blood cells clump together, blocking tiny blood vessels and causing severe pain and swelling in the affected parts of the body.

A new study from the Massachusetts Institute of Technology sheds light on how “vaso-occlusive” pain occurs.

“These painful crises are very unpredictable. In a way, we understand why they happen, but we don’t have a reliable way to predict them, ”says Ming Dao, chief scientist in the Department of Materials Science and Engineering at MIT and one of the senior authors of the study.

Sickle cell anemia is an inherited blood disorder in which red blood cells (erythrocytes) are sickle-shaped instead of the usual discoid.This is due to a mutation in the hemoglobin gene, as a result of which the red blood cells acquire a sickle shape and poorly carry oxygen.

To understand how red blood cells interact with blood vessels and cause vaso-occlusive pain, the researchers modeled a specialized microfluidic system that mimics the post-capillary vessels carrying deoxygenated blood from the capillaries.

One of the conditions of the experiment was to control the oxygen level.

Studies have shown that when oxygen levels are very low (hypoxia) similar to those observed in post-capillary vessels, sickle cells are two to four times more likely to attach to the walls of blood vessels than when oxygen levels are normal. At the same time, in a state of hypoxia, hemoglobin inside the sickle cells forms rigid fibers that grow and displace the cell membrane outward. These fibers also help cells adhere more tightly to the blood vessel endothelium.

The researchers also found that in patients with sickle cell disease, immature red blood cells called reticulocytes are more likely to adhere to blood vessels due to the fact that they have a larger cell membrane surface area than mature red blood cells, which allows them to create more adhesion sites.

Expert opinion:

Cell adhesion is indeed a very complex process. This discovery will help not only to understand in detail the mechanism of the occurrence of vaso-occlusive pain, but also to develop methods for predicting these crises in patients.

SICKLE ANEMIA | Encyclopedia Around the World

Contents of the article

SICKLE-CELL ANEMIA, hereditary human disease, in which red blood cells (erythrocytes), donating their oxygen, take on a bizarre elongated shape resembling a crescent or sickle. Normally, erythrocytes, giving off oxygen, change only color – bright red to bluish, but retain their usual rounded shape. With this disease, cells change not only color, but also shape.The immediate reason for this is a slight change in the chemical structure of hemoglobin, the main component of red blood cells. However, this change (replacement of only one amino acid in the protein part of the molecule) leads to the fact that the hemoglobin (hemoglobin S) formed in patients, giving off attached oxygen, becomes less soluble than normal hemoglobin (hemoglobin A), and turns into dense, semi-solid gel, which causes deformation of red blood cells. The synthesis of abnormal hemoglobin is generally referred to as hemoglobinopathy.

Sickle cell anemia is inherited, i.e. affects certain families, passing through the genes of parents to children. Thus, it can only be contracted by being born with a corresponding genetic disorder. If one of the family members is sick, sickle cells should be present in other family members, especially in parents and children, often in brothers and sisters, and often in more distant relatives.

The disease can be quite easy or very difficult.In the first case, symptoms occur rarely or only in special conditions. A very severe form usually leads to complete disability, proceeding with frequent attacks (crises) and shortening the life of patients. There are also intermediate forms of the disease, in which there are rarely such severe consequences and a longer life expectancy is possible, but they are also accompanied by crises from time to time.

Inheritance.

Studies have shown that a mild form of the disease is usually found in heterozygotes for this trait – in other words, in those who inherited the defective gene from only one parent and will pass it on to only half of their possible offspring.These persons have the so-called. heterozygous sickle cell anemia (S – A, or A – S). Although they themselves are practically not sick and may never get sick, they are still carriers of the disease, and – before special testing – latent carriers.

The most severe form of the disease affects homozygotes for the defective gene, i.e. inherited it from both mother and father; they will pass this gene on to all their descendants. Their condition is called homozygous sickle cell anemia (S – S).

An intermediate form of the disease is usually found in double heterozygotes, i.e.That is, individuals who are heterozygous for both this and any other hemoglobinopathy (for example, they synthesize hemoglobin C). In such cases, one speaks of S – C disease or some similar condition.

Prevalence.

Most affected families are of the black race, but the disease occurs in the white population as well. It is widespread in some African countries, in particular in Ghana, but in other regions, for example in South Africa, it is extremely rare.Sick families were also found in the southern regions of India, Italy, Greece and Turkey. In the western hemisphere, sickle cell disease affects people from Africa, India and the Mediterranean countries, regardless of where they live. This disease occurs throughout the United States and South America, but most often in areas where African Americans live. According to rough estimates, in the United States, one in 10 African Americans is a carrier of the disease, and one in 375 has an overt form; overall, the number of patients with sickle cell disease in the United States is estimated to exceed 50,000.

The mechanism of the disease.

In persons with sickle cell anemia, the majority of red blood cells retain their normal discoid shape. However, in certain circumstances, namely with a lack of oxygen, their shape changes. They become elongated, pointed and rigid, which prevents their free movement along the vascular bed and leads to blockage of blood vessels, especially the smallest ones. Due to insufficient blood supply to the tissues, the processes of decay and inflammation begin in them, causing pain and functional disorders.Most often, pain occurs in the limbs, abdomen, lower back, or in the head. The most commonly affected organs are the lungs, bones, spleen, kidneys, heart, and brain.

In addition to their bizarre shape, sickle cells are less durable than normal cells and have a shorter lifespan. Therefore, in patients with sickle cell anemia, despite the increased rate of erythrocyte formation, the hemoglobin content is reduced. They appear anemic and often somewhat icteric (due to the rapid breakdown of red blood cells).Growth and maturation are slowed down in childhood and adolescence. Patients are extremely susceptible to any infection; they tolerate malnutrition and dehydration worse, since the kidneys lose their ability to retain water; surgery and childbirth are more dangerous. It should be emphasized that complications and crises occur only from time to time. Even the most severely ill have long periods when they feel relatively healthy and can lead a normal life.

Diagnostic tests.

The diagnosis of sickle cell anemia is based on the analysis of the physical properties of hemoglobin. The first and oldest method of such analysis is the study of the so-called. “Wet smear”. When a blood smear is moistened with sodium metabisulfite, erythrocytes give off oxygen and under a microscope you can see a characteristic change in their shape. For greater accuracy, the study is repeated after 24 hours. Another, more common method is based on the detection of sickle cell hemoglobin by its reduced solubility in some buffer solutions, which is determined by the turbidity of a solution containing such hemoglobin.The widespread use of this method is associated with the ability to quickly obtain results (within 10-15 minutes).

Unfortunately, these methods do not allow distinguishing a heterozygous state from a homozygous one. Currently, this can only be done using hemoglobin electrophoresis, i.e. analysis of its mobility in an electric field. Neither accurate diagnosis nor reliable counseling is possible without such an analysis, but for mass examinations it is too expensive and time-consuming.

Treatment.

Today sickle cell anemia is an incurable disease. However, its identification is extremely important for the correct treatment of other diseases in these patients, as well as for providing them with adequate surgical and obstetric care. Correct management of patients with chronic sickle cell disease helps to prevent severe exacerbations (crises) and prolong life.

In some cases, the development of a severe crisis can be prevented by the rapid introduction of antibiotics in its early stages (to stop the infection) and the infusion of fluid (hydration).Oxygen, pain relievers, intravenous fluids, and antibiotics are commonly used to treat an advanced crisis. Sometimes it is necessary to resort to transfusion of red blood cells, as well as to use many other drugs, such as anticonvulsants, to relieve certain symptoms. See also ANEMIA.

90,000 The story of the first patient to receive CRISPR therapy for sickle cell disease

When Victoria Gray was three months old, doctors diagnosed her with sickle cell disease.The cause of this dangerous hereditary disease is a mutation in the hemoglobin gene, due to which red blood cells acquire a characteristic curved shape and cannot carry oxygen normally. Worse, at times, the deformed cells block the blood flow, causing severe bouts of pain and heart attacks.

Due to illness, Victoria was unable to play with other children and spent a lot of time in hospitals. As the girl grew older, she managed to go to college, but in the end anemia took its toll, forcing her to drop out and give up her dream of becoming a nurse.She later had to leave her job as a cosmetics saleswoman.

By the age of 34, Victoria, who lives in Mississippi, had two children. However, the girl still felt inferior, because she could not spend enough time with them and often went to hospitals – sometimes right in the middle of the night.

The girl considered the possibility of a bone marrow transplant, which is sometimes used to treat her illness. However, she knew that this was a very risky procedure.Fortunately, doctors offered Victoria another way – to participate in the first clinical trials of gene therapy for sickle cell disease using CRISPR. Unsurprisingly, she agreed.

With the patient’s consent, doctors at the Sarah Cannon Research Institute in Nashville, Tennessee began their procedures. They removed her bone marrow cells and used CRISPR to turn them on to produce fetal hemoglobin, which normally stops synthesizing immediately after birth.According to the doctors’ idea, this was to compensate for the malfunctioning of the “adult” hemoglobin and return some of the red blood cells to normal. After editing the cells, they were multiplied and injected back into the girl’s body. In total, she received 2 billion edited cells.

The operation took a lot of forces from Victoria. The most difficult was chemotherapy, which was needed to make room for the edited cells in the bone marrow.

After several months of waiting, the doctors told Victoria the news she had been waiting for: the transplanted cells began to produce fetal hemoglobin.Analysis showed that this type of hemoglobin made up half of all hemoglobin in her body. This is enough to relieve the symptoms of sickle cell disease. No side effects were identified.

However, the girl herself felt an improvement. Since the operation, she has had no bouts of pain, although they usually recur on a regular basis. In addition, all this time she did not need blood transfusions.

Physicians and researchers are extremely encouraged by Victoria’s findings.Encouraging news came from a second CRISPR patient, a German woman with beta-thalassemia. However, experts urge caution. It will take years to evaluate the results and possible side effects of the treatment.

Researchers in the United States have found a simple way to increase the efficiency of CRISPR by modifying the ends of the inserted genes. This paves the way for its widespread use in medicine.

Blood (part 3 of 8)

Erythrocytes

Erythrocytes

Number, shape and dimensions

Number, Shape and Size

The share of cellular elements accounts for 44% of the total blood volume.

The most numerous of them are red blood cells , or erythrocytes.

In men, 1 μl of blood contains an average of 5.1 million, and in women – 4.6 million erythrocytes.

Of the cellular components , which make up about 44 vol.% Of the blood,

the red corpuscles are the most numerous; men average 5.1 million, and women 4.6 million, per µl blood.

The main constituent of erythrocytes, in addition to water, is protein hemoglobin ,

, which accounts for 34% of the total mass and 90% of the mass of dried erythrocytes, i.e.that is, most of their mass.

Apart from their water content, the mass of the erythrocytes is chiefly composed of hemoglobin .

34% of their wet weight, and 90% of the dry weight, is attributable to this protein.

In childhood, the number of red blood cells gradually changes.

In newborns, it is quite high (5.5 million / μl of blood), which is due to the movement of blood from the placenta into the baby’s bloodstream during childbirth and a significant loss of water in the future.

During childhood the erythrocyte count changes.

In the newborn it is high (5.5 million per µl blood) because of the transfer of blood from the fetal placenta into the child’s circulation at birth and the subsequent marked water loss.

In the following months, the child’s body grows, but new erythrocytes are not formed ;

this is due to the “decline of the third month” (by the third month of life, the number of erythrocytes decreases to 3.5 million./ μL of blood).

In children of preschool and school age, the number of erythrocytes is slightly less than in women.

In the following months the production of erythrocytes does not keep pace with general body growth,

so that the “trimester reduction” develops (a decrease in erythrocyte count to about 3.5 million per µl blood in the third month of life).

Preschool and school children have somewhat lower erythrocyte counts than adult women.

Shape and size of erythrocytes.
Shape and size of the erythrocytes.

Human erythrocytes are non-nucleated flat disc-shaped cells.

Their maximum thickness (at the edges) is only 2 microns.

Their distribution by diameter in a healthy person corresponds to the normal distribution curve, or Price-Jones curve (Fig.6).

The average value of the diameter of an erythrocyte ( normocyte ) in an adult is 7.5 microns.

Human erythrocytes are flat, round disks without nuclei , indented in the middle on both sides.

Their greatest thickness (at the edge) is only 2 µm;

their diameters, in healthy people, form a normal distribution, the Price-Jones curve (Fig.6), about a mean of 7.5 µm ( normocyte ).

Fig. 6. Price-Jones curve. Distribution of erythrocyte diameters in a healthy person (red line) and in a patient pernicious anemia (black line) Fig. 6. Price-Jones curves. Frequency distribution of erythrocyte diameter in a healthy person (red line) and in a patient with pernicious anemia (black line).

Due to the double-curved shape of the normocyte, its surface is larger than if it had the shape of a ball.

The total surface area of ​​adult erythrocytes is about 3800 m 2 .

The special shape of erythrocytes contributes to the performance of their main function – – the transfer of respiratory gases , since with this form the diffusion surface increases, and the diffusion distance decreases.

The biconcave shape of the normocyte results in an increase in surface area, as compared with a sphere.

the total surface area of ​​the erythrocytes of an adult man is about 3,800 m 2 .

The main function of the erythrocyte, gas transport , is facilitated by this characteristic shape, for the diffusion area is large and the diffusion distance small.

In addition, due to their shape, erythrocytes have a greater ability to reversible deformation when passing through narrow curved capillaries .

As cells of age, the plasticity of erythrocytes decreases.

Moreover, it is easier for cells so shaped to be reversibly deformed in order to pass through narrow, curved capillaries .

The plasticity of the erythrocyte is less in older cells.

Plasticity is also reduced in erythrocytes with pathologically altered form (for example, in spherocytes and sickle-shaped erythrocytes ),

which is one of the reasons for the delay and destruction of such cells in reticular tissue spleen .

It is also reduced in pathological forms of erythrocytes, such as spherocytes and sickle cells ;

the loss of plasticity is one reason why such cells are retained in the meshwork of the spleen and subsequently destroyed there.

Methods for counting erythrocytes. Principle of erythrocyte counting.

To calculate the exact measured amount of capillary blood, dilute with isotonic saline solution 100-200 times.

Under a microscope , the number of cells in a certain volume of such a suspension is counted.

To determine the total number of cells in of the original blood , recalculate , taking into account the dilution of .

A measured quantity of capillary blood is diluted 100- or 200-fold with isotonic saline solution .

The cells in a specified volume of this mixture are counted by microscopic examination ,

and the dilution factor is applied to determine the cell count in the original blood .

Recently, more and more accurate methods are used more and more , without using a microscope .

The content of erythrocytes in the solution is determined by the degree of scattering of the light beam passing through it or by the change in electrical conductivity in a thin tube when cells pass through it.

In recent years it has become increasingly common to use more precise, non-microscopic procedures .

The erythrocyte concentration in a diluted suspension is determined from the degree of scatter of transmitted light , or from the changes in electrical conductance observed during passage of the cells through a thin tube.

At violation of erythropoiesis there is a shift of the Price-Jones curve to the right;

here we are talking about macrocytosis , i.e. a significant increase in the number of erythrocytes with a diameter exceeding 8 microns.

With pernicious anemia , the diameter of individual erythrocytes ( megalocytes ) sometimes exceeds 12 microns.

When impairment of the erythropoietic system causes a shift of the Price-Jones curve to the right – i.e., a significant increase in the number of erythrocytes over 8 µm in diameter – the condition is termed macrocytosis .

In pernicious anemia some of the erythrocytes ( megalocytes ) can have diameters of over 12 µm.

A shift of the Price-Jones curve to the left (i.e., a significant increase in the number of red blood cells with a diameter of less than 6 microns) is called microcytosis .

In this case, dwarf erythrocytes with a shortened life span are found in the blood ;

their diameter can be only 2.2 microns.

A leftward shift of the Price-Jones curve (a significant increase in the number of erythrocytes with diameters <6 µm) is called microcytosis .

The diameter of these short-lived dwarf forms can be as little as 2.2 µm.

A flatter shape of the Price Jones curve as a result of an increase in the number of both macrocytes and microcytes is characteristic of anisocytosis of a.

Pernicious anemia and thalassemia are accompanied by poikilocytosis – a condition in which red blood cells of various unusual shapes are found.

Round spherocytes (with spherocytosis ) and sickle erythrocytes (with sickle cell anemia ) belong to erythrocytes with a characteristic pathologically altered shape.

When the Price-Jones curve is flattened, as a result of the simultaneous increase in both macro- and microcytes, a state of anisocytosis exists.

Poikilocytosis , in which there is abnormal variation in erythrocyte shape, can accompany pernicious anemia and thalassemia .

Among the characteristically altered cells are rounded spherocytes ( spherocytic anemia ) and sickle cells ( sickle-cell anemia ).

Formation, life expectancy and destruction of erythrocytes

Production, Life Span and Destruction

Erythropoiesis.
Erythropoiesis.

Erythrocytes are formed in hematopoietic tissues yolk sac in the embryo, liver and spleen in fetus and red bone marrow flat bones in an adult.

All these organs contain the so-called pluripotent stem cells – the common precursors of all blood cells .

Erythrocytes are produced in the hemopoietic tissues – the yolk sac of the embryo, the liver and spleen of the fetus , and the red marrow of the flat bones in adults.

These structures contain the pluripotent stem cells , the common progenitors of all kinds of blood cells.

At the next (according to the degree of differentiation) level there are committed precursors , of which only one type of blood cells can already develop (erythrocytes, monocytes , granulocytes , platelets or lymphocytes ).

After several more stages of differentiation and maturation, young non-nuclear erythrocytes leave the bone marrow in the form of the so-called reticulocytes (Fig.five).

At the next level of differentiation are the committed progenitors , capable of forming only one kind of blood cell (erythrocyte, monocyte , granulocyte , thrombocyte or lymphocyte ).

Several stages of differentiation and maturation are distinguished, until finally the young, anuclear erythrocyte leaves the bone marrow as a reticulocyte (Fig.five).

Fig. 5. Cells of peripheral blood and their precursors in hematopoietic organs – bone marrow and lymphatic system Fig. 5. The cells found in peripheral blood and their precursors in the germinal centers, the bone marrow and lymphatic system.

Ripe red blood cells circulate in the blood for 100-120 days,

after which are phagocytized by cells of the reticuloendothelial system of the bone marrow (and in case of pathology also of the liver and spleen).

Erythrocytes circulate in the blood for 100-120 days.

Then they are phagocytized by cells of the reticuloendothelial system in the bone marrow, and under pathological conditions also in the liver and spleen.

However, not only these organs, but any other tissue is capable of destroying blood cells, as evidenced by the gradual disappearance of “bruises” ( subcutaneous hemorrhages ).

In the body of an adult, there are 25 • 10 12 erythrocytes, and about 0.8% of their number is renewed every 24 hours.

In fact, as is evident in the gradual disappearance of the “black and blue” marks caused by intracutaneous bleeding , any tissue is capable of degrading blood corpuscles.

About 0.8% of the 25 • 10 12 erythrocytes of an adult are renewed in 24 hours.

This means that 160-106 erythrocytes are formed in 1 minute.

After blood loss and with pathological shortening of the life of erythrocytes the rate of erythropoiesis can increase several times.

This implies an erythropoiesis rate of 160-10 6 erythrocytes / min.

After loss of blood , and when the erythrocyte life span is pathologically shortened, the erythropoiesis rate can increase severalfold.

A powerful stimulant of erythropoiesis is a decrease in the partial pressure of O 2 (i.e.i.e., the discrepancy between the tissue demand for oxygen and its supply).

This increases the content in the plasma of a special substance that accelerates erythropoiesis – erythropoietin .

The effective stimulus that triggers erythropoiesis is a fall in the O 2 partial pressure in respiring tissue (an imbalance between O 2 supply and demand).

Under such conditions there is an increased plasma concentration of a hormone called erythropoietin , which accelerates erythropoiesis.

In humans, erythropoietin is thermostable glycoprotein with a molecular weight of about 34,000 and a sugar content of 30%.

The protein part of erythropoietin includes 165 amino acid residues;

has recently been identified for its amino acid sequence.

The kidneys play the main role in the synthesis of erythropoietin;

with bilateral nephrectomy , the concentration of erythropoietin in the blood decreases sharply.

Synthesis of erythropoietin is also inhibited in various renal diseases.

Human erythropoietin is a heat-stable glycoprotein (MW ca. 34,000; 30% sugar),

the amino acid sequence of which has recently been established (165 amino acids) .The kidneys play a central role in the synthesis of erythropoietin; the blood erythropoietin concentration falls sharply after bilateral nephrectomy , and the synthesis of erythropoietin is also reduced in various kidney diseases.

Previously, it was believed that the kidneys themselves do not produce erythropoietin , but secrete a certain enzyme , which breaks down plasma globulin with formation of this hormone .

However, it has recently been shown that the kidneys contain both active erythropoietin and messenger RNA ( mRNA ), which controls its synthesis.

In small amounts, erythropoietin is also formed in other organs – mainly in the liver.

The kidneys were once thought not to synthesize erythropoietin themselves but rather to release an enzyme that cleaves the hormone from a plasma globulin.

But recently the kidney has been found to contain both the active hormone and the messenger ribonucleic acid ( mRNA ) that initiates the synthesis of erythropoietin.

Small amounts are also synthesized extrarenally , primarily in the liver.

Erythropoietin stimulates differentiation and accelerates the multiplication of erythrocyte precursors in the bone marrow (Fig. 5).

All this leads to an increase in the number of hemoglobin-forming erythroblasts .

The action of erythropoietin is enhanced by many other hormones, including androgens , thyroxine and growth hormone .

Differences in the number of red blood cells and hemoglobin content in the blood of men and women (see.above) are due to the fact that androgens enhance erythropoiesis, and estrogens inhibit it.

Erythropoietin stimulates the differentiation and accelerates the proliferation of the erythrocytic progenitors in the bone marrow (Fig. 5), thus increasing the number of hemoglobin-forming erythroblasts .

Various other hormones, including androgens , thyroxine and growth hormone , enhance the action of erythropoietin.

The differences in erythrocyte count and hemoglobin concentration in the blood of men and women result from the fact that erythropoiesis is promoted by androgens and inhibited by estrogens.

Reticulocytes.
Reticulocytes.

Counting reticulocytes in the blood (Fig. 5) can provide important information for diagnosis and treatment of the state of erythropoiesis.

These cells serve as direct precursors of erythrocytes.

Counts of the reticulocytes in the blood (Fig. 5) can give information about erythropoiesis that is useful in diagnosis and therapy.

Reticulocytes are the stage immediately preceding the mature erythrocyte.

Unlike erythrocytes, in which light microscopy does not reveal cell structures , in reticulocytes by the method of vital staining (for example, diamond cresol blue), granular or filamentous structures can be detected.

These young blood cells are found in both the bone marrow and peripheral blood .

Whereas the latter has no intracellular structures visible by light microscopy , vital staining of the reticulocytes (staining of the living cells with, e.g., brilliant cresyl blue) reveals granular or filamentous structures .

These young blood cells can be found in bone marrow and in the circulating blood .

Normally, reticulocytes make up 0.5-1% of the total number of red blood cells;

when erythropoiesis is accelerated, the proportion of reticulocytes increases, and when it slows down, it decreases.

Under normal conditions they account for 0.5 – 1% of the erythrocytes in healthy blood.

Any acceleration of erythropoiesis increases this percentage, and any retardation decreases it.

In cases of increased destruction of erythrocytes, the number of reticulocytes may exceed 50%.

With sharply accelerated erythropoiesis, even normoblasts sometimes appear in the blood.

When the rate of erythrocyte degradation rises, the proportion of reticulocytes can increase to over 50%.

In cases of excessively rapid erythropoiesis, even normoblasts can occasionally appear in the blood.

Anemia literally means bloodless.

In the clinic, this term denotes, first of all, a decrease in the ability of blood to carry oxygen due to a lack of hemoglobin.

Anemia means, literally, bloodlessness.

In clinical usage, the term refers primarily to the diminished ability of the blood to transport oxygen , because of the lack of hemoglobin.

With anemia, either the number of erythrocytes or the content of hemoglobin in them may decrease, or both.

The term “anemia” does not indicate the reasons for the lack of hemoglobin.

In this state, there can be a reduction in the number of erythrocytes as compared with the norm and / or in the hemoglobin content of the individual erythrocytes.

The term “anemia” implies nothing about the causes of the hemoglobin deficiency.

Most common iron deficiency anemia .

It may be due to a lack of iron in food (especially in children),

disorders of iron absorption in the digestive tract (for example, with the so-called malabsorption syndrome ) or

chronic blood loss (for example, with peptic ulcer , tumors , polyps and diverticula of the gastrointestinal tract , varicose veins of the esophagus , helminthic invasion , common in tropical countries, and with abundant menstrual bleeding ).

In iron deficiency anemia, the blood contains small erythrocytes with a low hemoglobin content ( hypochromic microcytic anemia ).

The most common form of anemia is iron-deficiency anemia .

This can be produced by a diet with inadequate iron content (especially common among infants),

by diminished iron absorption from the digestive tract (for example, in the so-called malabsorption syndrome ),

or by chronic loss of blood due, for example, to ulcers , carcinomas and polyps and diverticuli in the gastrointestinal tract ,

esophageal varicosities,

hookworm infestation (common in the tropics),

and heavy menstrual bleeding.

In iron-deficiency anemia the blood contains small erythrocytes with a subnormal hemoglobin content ( hypochromic microcytic anemia ).

Another type of anemia, megaloblastic anemia ,

is characterized primarily by the presence in the blood and bone marrow of pathologically enlarged erythrocytes (megalocytes) and their immature precursors ( megaloblasts ).

Another group of anemias is termed megaloblastic anemia ;

the most important common characteristic of these anemias is the presence of abnormally large erythrocytes ( megalocytes ) and their immature precursors ( megaloblasts ) in the blood and bone marrow.

The formation of these giant cells is associated with a lack of substances that contribute to the maturation of erythrocytes vitamin B12 (with pernicious anemia) and / or folic acid .

The deficiency of these substances, caused by their insufficient content in food or poor absorption, leads to a slowdown of cell division , although the growth rate of the latter remains almost unchanged;

as a result, pathologically enlarged cells are formed.

Anemia in this case occurs due to the fact that the life span of megalocytes compared to red blood cells is shorter, as well as due to the slow maturation of red blood cells.

Production of these giant cells is caused by a deficiency of the erythrocytematuration substances vitamin B12 ( pernicious anemia ) and / or folic acid , due to inadequacies in either diet or absorption.

When these substances are lacking, cell division is delayed although the rate of growth hardly changes,

so that the cells develop to an abnormally large size.

Megalocytes have a shorter life span than normal erythrocytes and this, together with the delayed maturation of erythrocytes, leads to anemia.

In some pathological conditions, due to increased fragility of erythrocytes, the rate of hemolysis increases .

If the formation of erythrocytes does not compensate for their accelerated destruction, hemolytic anemia occurs.

Pathological states in which the rate of hemolysis increases, because the erythrocytes have become more vulnerable to degradation,

can give rise to hemolytic anemia if the production of erythrocytes cannot keep pace with the accelerated destruction.

Similar conditions are observed with congenital forms of spherocytosis and such hereditary diseases as sickle cell anemia and thalassemia.

This category includes anemia in malaria, accelerated hemolysis as a result of autoimmune reactions and erythroblastosis of newborns (anemia associated with Rh incompatibility ).

Examples of this condition include the heriditary form of spherocytosis and the (also hereditary) diseases sickle-cell anemia and thalassemia.

The anemia that accompanies malaria, accelerated hemolysis due to autoimmune response s and erythroblastosis fetalis (anemia caused by incompatibility of rhesus factors ) are also in this category.

For aplastic anemias and pancytopenia , inhibition of bone marrow hematopoiesis is characteristic, despite the normal content of all necessary substances.

In aplastic anemia, only erythropoiesis is suppressed, and in the case of pancytopenia, the content of all blood cells produced by the bone marrow decreases.

Cases of aplastic anemia and pancytopenia are characterized by diminished cytogenesis in the bone marrow, even though all the materials necessary for the production of blood cells are present.

In the aplastic anemia only the erythrocytes are affected, whereas in the pancytopenias all the blood cells produced in the bone marrow are reduced in number.

Aplastic anemias can be either hereditary (Diamond Blackfen anemia, Fanconi syndrome) or acquired ( idiopathic ).

Inhibition of hematopoiesis in pancytopenia can be associated with damage to the bone marrow ionizing radiation (under the action of X-rays or radioactive elements), cell poisons ( cytostatics , benzene, etc.)or metastases of tumors , growing in the place of normal tissue.

Among the aplastic anemias are both hereditary (Diamond-Blackfan, Fanconi) and acquired, idiopathic forms.

The inhibition of cell production in the pancytopenias can be caused by bone-marrow damage due to ionizing radiation (X rays or exposure to radioactive elements), cell toxin s ( cytostatics , benzene etc.), or tumor metastases , which take the place of normal tissue.

Metabolism and properties of erythrocyte membranes

Metabolism and Membrane Properties

The metabolism of mature non-nuclear erythrocytes is aimed at ensuring their function as oxygen carriers, as well as their participation in the transfer of carbon dioxide.

In this regard, the metabolism of erythrocytes differs from the metabolism of other cells.

The metabolic activity of the mature, anuclear erythrocyte is specialized for its oxygen-transporting function and its intermediary role in the transport of carbon dioxide.

Erythrocyte metabolism is thus unlike that in the other cells of the body.

It must first of all support the ability of the erythrocyte to reversibly bind oxygen , which requires the reduction of the iron ion in the heme.

Ferrous iron in it constantly transforms into trivalent due to spontaneous oxidation of and, in order for oxygen binding to occur, Fe (III) must be reduced to Fe (II) .

One of its prime tasks is to maintain the cell’s ability to bind oxygen reversibly, not least by providing a means for reduction of the heme ion.

The ferrous iron it contains is continually changed to the ferric state by spontaneous oxidation , and must be returned to the ferrous form before it can again combine with oxygen.

The precursors of erythrocytes containing the nucleus possess the usual set of enzymes required both for energy production from oxidative processes and for the synthesis of proteins.

In mature erythrocytes, only glycolysis can take place, the main substrate of which is glucose.

The main source of energy in erythrocytes, as in other cells, is ATP.

This substance is necessary, in particular, for the active transport of ions across the erythrocyte membrane, i.e. to maintain an intracellular ion concentration gradient.

Whereas the nucleated precursors of the erythrocytes contain the familiar enzymes for the oxidative release of energy and protein synthesis,

the mature erythrocyte must rely on glycolysis , with glucose as the chief substrate.

The main energy source, as in other cells, is ATP;

it is required in particular for the active transport of ions through the erythrocyte membrane and thus serves to maintain the intracellular ion-concentration gradient.

Along with the synthesis of ATP in the process of glycolysis in erythrocytes, the formation of reducing agents also occurs – NADH (reduced nicotinamide adenine dinucleotide ) and NADPH (reduced nicotinamide adenine dinucleotide phosphate , formed in pentose).

NADH is used for the aforementioned reduction of methemoglobin into hemoglobin capable of binding oxygen, and NADPH is used for the reduction of glutathione .

The easily oxidized glutathione protects against oxidation and inactivation a number of important enzymes containing SH-groups (in particular, enzymes associated with the hemoglobin molecule and the cell membrane).

When ATP is derived from glycolysis, reducing substances such as NADH (reduced nicotinamide-adenine dinucleotide) and NADPH (reduced nicotinamide-adenine dinucleotide phosphate , derived from the pentose-phosphate cycle) are produced as well.

NADH is required for the above-mentioned reduction of methemoglobin to hemoglobin, which can bind oxygen;

NADPH is involved in the reduction of the glutathione in the erythrocyte.

Glutathione, which is readily oxidizable , protects a number of important enzymes with SH groups in the cell (especially those associated with the hemoglobin molecule and the cell membrane) from inactivation by oxidation.

The erythrocyte membrane is a plastic molecular mosaic consisting of proteins, lipo- and glycoproteins and, possibly, purely lipid regions.

Its thickness is about 10 nm;

it is about a million times more permeable to anions than to cations.

The erythrocyte membrane is a flexible molecular mosaic composed of protein, lipo- and glycoproteins and, probably, regions of pure lipoid.

The membrane is about 10 nm thick;

it is about a million times more permeable to anions than to cations.

The transfer of substances through the membrane takes place, depending on their chemical properties, in different ways:

either hydrodynamically (by diffusion), when substances in the form of a solution pass through membrane pores filled with water, or, if substances are soluble in fats , by penetration through lipid sites.

Some substances can interact with embedded in the membrane carrier molecules , forming an easily reversible bond with them, and then either passively or as a result of the so-called active transport pass through the membrane.

Substances that can pass through the membrane do so in several ways, depending on their chemical properties:

by diffusion or hydrodynamically, moving as a solution through water-filled membrane pores, or – if they are lipid-soluble – by penetrating the lipoid areas.

Certain substances can be bound in readily reversible form to carrier molecules in the membrane, and are thus channelled through the membrane either passively or by way of so-called active transport.

Special physical and chemical properties of erythrocytes

Special Physicochemical Properties

Plasticity.
Deformability.

Normal erythrocyte is able to easily change its shape under the influence of external forces.

It is due to this that the erythrocytes pass through the capillaries, the inner diameter of which is less than the diameter of the free erythrocyte (7.5 microns).

The shape of a normal erythrocyte can easily be changed by external forces.

As a result, the cells can pass through capillaries with inside diameter smaller than the mean diameter of a free erythrocyte (7.5 µm).

Due to this plasticity of erythrocytes , the relative viscosity of blood in small vessels is significantly less than in vessels whose diameter is much greater than 7.5 microns.

This property of erythrocytes is associated with the presence of type A hemoglobin in them.

In some hereditary hemoglobinopathies erythrocytes become more rigid, which leads to impaired blood flow .

Because of this deformability , the relative viscosity of the blood in small-bore vessels is effectively lower than in vessels of diameter well above 7.5 µm.

The plasticity of the erythrocyte is associated with the presence of Type A hemoglobin;

in certain hereditary hemoglobinopathies the cells are much more rigid and circulation is impeded .

Osmotic properties.
Osmotic properties.

The content of proteins in erythrocytes is higher, and low-molecular substances are lower than in plasma.

Osmotic pressure , created by a high intracellular concentration of proteins, is largely compensated by a low concentration of low molecular weight substances,

therefore osmotic pressure in erythrocytes is only slightly higher than in plasma: its value is just enough to provide normal turgor of these cells.

The concentration of protein in the erythrocyte is higher than in plasma, and that of small molecules is lower.

The osmotic effect of the higher internal protein concentration is to a great extent compensated by the lower concentration of small molecules,

so that the intracellular osmotic pressure is only slightly higher than that of the plasma, and just suffices for the normal turgor of the erythrocyte.

The erythrocyte membrane is, in principle, permeable to small molecules and ions (for different in varying degrees).

Because of this permeability, inhibition of active transport of ions (Na + and K + are actively transported across the membrane: Na + from the cell, and K + – into the cell; Fig. 2) leads to a decrease in their transmembrane concentration gradients.

High intracellular protein content, which at the same time remains constant, ceases to be compensated, and the osmotic pressure in the erythrocyte increases.

(Na + and K + are actively transported through the membrane, Na + out of the cell and K + into it; cf. Fig. 2).

In principle, the erythrocyte membrane is permeable to small molecules, to different degrees depending on the ion concerned.

Because of this permeability, inhibition of the active transport of ions results in a reduction of their transmembrane concentration gradient,

so that the continued high intracellular protein concentration is no longer compensated, and the osmotic pressure increases.

As a result, water begins to flow into the erythrocyte;

this continues until its membrane bursts and hemoglobin is released into the plasma.

The process is called osmotic ( colloid osmotic ) hemolysis .

If the extracellular fluid is only moderately hypotonic , erythrocytes swell and acquire a shape close to spherical ( spherocytes ).

Therefore water flows into the erythrocyte, until the membrane bursts and hemoglobin emerges into the plasma – a process called ( colloid ) osmotic hemolysis .

When the extracellular fluid is only slightly hypotonic , the erythrocytes swell and approach a spherical shape ( spherocytes ).

On the contrary, in hypertonic environment they lose water and shrink (Fig.7). In a hypertonic medium the cells lose water and become crenated (Fig. 7).

Fig. 7.

A. Normal erythrocytes in the form of double-concave disc a.

B. Shrunken erythrocytes in hypertonic saline

Fig.7.

Left: biconcave discoid shape of normal erythrocytes.

Right: crenated erythrocyte , the result of exposure to

hypertonic saline solution.

A study of the osmotic resistance of erythrocytes in environments with increasing hypotonicity showed that in a number of diseases (in particular, in some types of anemias), their osmotic resistance changes.

From the curve in Fig. 8 it can be seen that 50% of erythrocytes of a healthy person are hemolyzed by in a NaCl solution at a concentration of 4.3 g / L.

Systematic study of the osmotic resistance of erythrocytes suspended in media of progressively reduced osmotic pressure has demonstrated that in some diseases, certain forms of anemia in particular, osmotic resistance is changed.

The curve in Fig. 8 shows that 50% of the erythrocytes of a healthy person are hemolyzed when the tonicity of the medium reaches 4.3 g • l-1 NaCl.

Fig. 8. Osmotic resistance erythrocytes (norm and range of deviations) in blood diluted with NaCl solutions in a ratio of 1:40.

The abscissa is the concentration of the solution in percent (g / dl).

On the ordinate axis, the degree of hemolysis (as a percentage of the total), determined by photometric method

Fig.8. Osmotic resistance of erythrocytes in a blood sample diluted 1:40 with solutions of the indicated salinity.

Normal curve with range of deviation.

Ordinate: photometrically determined degree of hemolysis as% of total hemolysis.

Abscissa: salinity of NaCI solution in% (g / dl).

Osmotic hemolysis of erythrocytes also occurs in isotonic solutions of substances that easily penetrate through their membranes (for example, in a urea solution).

Urea is evenly distributed between the erythrocyte and the external environment.

Osmotic hemolysis also occurs when erythrocytes are suspended in an isosmotic solution of substances, such as urea, to which the membrane is highly permeable.

Urea becomes uniformly distributed within the erythrocyte and in the suspension medium.

Since the cell membrane retains large molecules inside the erythrocyte, the osmotic pressure in it becomes greater than in the external environment;

the difference between extracellular and intracellular osmotic pressure in this case will be proportional to the amount of absorbed urea.

Water begins to enter the erythrocyte, which leads to rupture of the membrane.

Because the erythrocyte membrane prevents the larger molecules from leaving the cell, the intracellular osmotic pressure rises above that of the medium, in proportion to the influx of urea.

Water enters the cell and causes mechanical disruption of the membrane.

Hemolysis can also occur as a result of the action of fat-dissolving substances (for example, chloroform, ether, etc.).

These substances wash lipids from the erythrocyte membrane, leaving holes in it.

The hemolytic effect of soaps, saponins and synthetic detergents is due to the fact that they reduce the surface tension between the aqueous and lipid phases of the membrane.

Finally, lipid solvents such as chloroform, ether and the like can make leaks in the membrane by dissolving out its lipid components, which also leads to hemolysis.

The hemolytic effect of soaps, saponins and synthetic detergents results from reduction of the surface tension between the aqueous and lipid phases of the membrane.

This leads to the emulsification of fats, washing them out of the membrane and the formation of holes in it through which the contents of the cell escape. The lipids are emulsified and drawn out of the membrane, leaving holes through which the cell contents emerge.
Erythrocyte sedimentation rate.
Sedimentation rate of blood corpuscles.

Specific gravity of erythrocytes (1.096) is higher than the specific gravity of plasma (1.027), therefore, in a test tube with blood, which is deprived of the ability to clot , they slowly settle to the bottom.

The erythrocyte sedimentation rate (ESR) in a healthy man in the first hour is 3-6 mm, and in a woman – 8-10 mm.

The specific weight of erythrocytes (1.096) is higher than that of plasma (1.027), so that in an anticoagulated blood sample they slowly sink toward the bottom.

The erythrocyte sedimentation rate (ESR) of a healthy man is 3-6 mm in the first hour;

the value for women is 8-10 mm.

In some pathological conditions (in particular, with inflammatory diseases and with tumors , accompanied by increased tissue decay ) ESR is increased mainly due to the tendency of erythrocytes to form aggregates .

The resistance of such aggregates to friction is less than the total resistance of their constituent elements, since during the formation of aggregates the ratio of surface to volume decreases ; in this regard, they settle faster.

Sedimentation is more rapid in certain pathological states (particularly inflammation and increased tissue breakdown due to tumors ), chiefly because of the greater tendency for the red cells to gathering into clumps .

The frictional resistance of such an aggregate is less than the total resistance of its individual elements because of the smaller surface-to-volume ratio , so that the aggregates sink more rapidly.

ESR is primarily influenced by the protein composition of blood plasma.

Erythrocytes of a patient with increased ESR , as a rule, settle at a normal rate in the blood plasma of the same group from a healthy person.

ESR is influenced primarily by the composition of the plasma proteins.

Erythrocytes from a patient with accelerated ESR as a rule sink at the normal rate when introduced into plasma of the same blood type from a healthy person.

On the contrary, the erythrocytes of a healthy individual are deposited in the patient’s plasma at an increased rate.

ESR decreases with an increase in the content of albumin in the plasma and increases with an increase in the concentration of fibrinogen, haptoglobin , ceruloplasmin and α- and β-lipoproteins, as well as immunoglobulin paraproteins formed in excess in some pathological conditions.

Conversely, erythrocytes from the healthy subject sink more rapidly in the patient’s plasma.

ESR is retarded by increase in the plasma albumin concentration, and accelerated by increase in the concentration of fibrinogen, haptoglobin , ceruloplasmin , α and β-lipoproteins and paraproteins (immunoglobulins produced in abnormally large numbers in certain illnesses) …

Each of these factors can enhance the influence of the other.

Plasma proteins that accelerate erythrocyte sedimentation are called agglomerins .

The fact that albumin and globulins have opposite effects on ESR explains the long-known effect of increasing ESR when the albumin-globulin coefficient shifts towards an increase in the amount of globulins.

The effects of each of these plasma components are additive.

Plasma proteins that accelerate sedimentation are called agglomerins .

The observation that albumin and globulin have opposite effects on ESR explains the earlier finding that shift of the albumin-globulin ratio in favor of globulin is associated with an increased sedimentation rate.

ESR increases with a significant decrease in the number of erythrocytes (hematocrit), as this decreases blood viscosity, while increasing hematocrit, the opposite picture is observed.

A marked reduction of cell concentration (lowered hematocrit) reduces the viscosity of the blood and thus accelerates sedimentation;

increase in the hematocrit has the reverse effect.

If the shape of erythrocytes is either changed (for example, in sickle cell anemia), or varies greatly (the latter condition is called poikilocytosis and occurs, in particular, in pernicious anemia), then the aggregation of erythrocytes is suppressed and ESR decreases.

Many steroid hormones (estrogens, glucocorticoids) and drugs (for example, salicylates) cause an increase in ESR.

Change of erythrocyte shape, as occurs in sickle-cell anemia, and extreme nonuniformity of shape (poikilocytosis, as in pernicious anemia) interfere with aggregation and thus reduce the ESR.

Various steroid hormones (estrogens, glucocorticoids) and medicines (e.g., salicylate) raise the ESR.

ESR is most often measured using the Westergren method.

For this purpose, 1.6 ml of blood is taken from the cubital vein with a 2 ml syringe containing 0.4 ml of a 3.8% solution of Na citrate (to prevent clotting).

Measurement of ESR is most commonly done by Westergren’s method.

1.6 ml of blood are withdrawn from the cubital vein with a 2-ml syringe containing 0.4 ml 3.8% sodium citrate solution to prevent clotting.

A test tube with an inner diameter of 2.5 mm, calibrated in millimeters on a 200 mm segment (the so-called Westergren tube ), is filled with the resulting solution to the zero mark and strengthened in an upright position.

After some time (usually after 1 or 2 hours), the height of the liquid column that does not contain erythrocytes ( supernatant ) is noted.

A Westergren tube (2.

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