Denture Induced Submandibular Hematoma in a Patient on Warfarin

A 79-year-old lady, who was taking warfarin, presented to the Emergency Department with a painless anterior neck swelling, which was associated with hoarseness of voice, odynophagia, and shortness of breath. She first noticed the swelling after she removed her dentures in the evening. On examination, she had an increased respiratory rate. There was a large submandibular swelling at the anterior side of her neck. Upon mouth opening, there was a hematoma at the base of her tongue, which extended to both sides of the tonsillar pillars. The patient was intubated with a video laryngoscope due to her worsening respiratory distress. Intravenous vitamin K and fresh frozen plasma were given immediately. The patient was admitted to the ICU for ventilation and observation. The hematoma subsided after 2 days and she was discharged well.

1. Introduction

There are few reports of upper airway hematomas after anticoagulation following minor intraoral trauma. Although some cases can be treated conservatively, others may progress to life-threatening situations. This is an interesting case of a patient with warfarin, who presented with upper airway hematoma after the use of her dentures. The management is also discussed.

2. Case Report

A 79-year-old lady presented to the Emergency Department with a painless anterior neck swelling. The swelling appeared one day before and was gradually increasing in size. She first noticed the swelling after she removed her dentures in the evening. Several hours later, she developed hoarseness of voice, odynophagia, and mild shortness of breath. There was no hematemesis, melena, or any neurological deficits. On further questioning, she had a history of hypertension and atrial fibrillation. She has been taking amlodipine and warfarin but was not compliant to her medication and follow-ups. She was supposed to be on warfarin of 3mg per day. However, she did not present herself to the clinic for warfarin optimization, and no INR was done.

On examination, she was fully conscious. However, an audible stridor was heard. Her blood pressure was 130/90mmHg, heart rate 92/min, respiratory rate 24/min, and oxygen saturation 95% on room air. There was a large submandibular swelling at the anterior side of her neck. The mass extended to the left side of neck and was 8cm by 6cm in size. The skin overlying the swelling was bluish-red, and there was tenderness on palpation. Upon mouth opening, there was a hematoma at the base of her tongue which extended to both sides of the tonsillar pillars. The uvula appeared edematous and engorged. There was limitation in mouth opening due to the pain. Bleeding was seen from the base of the tongue when her tongue was protruded.

Blood investigations revealed hemoglobin of 12.4g/dl, platelet 274 x 10⁹/liter, with normal electrolytes. The Prothrombin Time (PT) and Partial Thromboplastin Time (PTT) were prolonged for more than 2 minutes and INR was 8.0. A flexible nasoendoscopy done by the otorhinolaryngologist found a huge swelling at the laryngeal area. The vocal cords were not visible. There were blood clots covering both the arytenoids and epiglottis.

The patient was planned for tracheal intubation due to her worsening respiratory distress. Intravenous vitamin K and fresh frozen plasma (FFP) were given immediately.

Anaesthetic management at that time was gas induction with Sevoflurane in incremental concentration until loss of consciousness with preservation of spontaneous breathing. Muscle relaxants were not used. A D-blade video laryngoscope CMAC was used. During intubation, it was noted that the laryngeal apertures were grossly engorged and swollen. The oral structures were beyond recognition. Blood clots were seen covering the pharyngeal walls, epiglottis, and arytenoids. The vocal cords were not prominently visualized. As the patient was spontaneously ventilated, air bubbles were seen from the posterior side of the engorged epiglottis. This served as a guide for tracheal tube insertion (Video 1). A size 6 endotracheal tube was used to secure the airway. It was a successful intubation only at the second attempt. Hemodynamics were stable throughout the procedure.

The patient was sent to the ICU for ventilation and observation. The hematoma at the neck and base of tongue subsided after 2 days. Her INR was 2.0, and she was discharged from the ICU soon after that.

3. Discussion

Anticoagulants are used for prophylaxis and treatment of thromboembolic diseases, acute ischemic strokes, deep venous thrombosis, pulmonary emboli, heart valve diseases, acute myocardium infarction, and atrial fibrillation. Warfarin (brand names Coumadin) is a first generation oral anticoagulant agent. It works by inhibiting the production of vitamin-dependent coagulation factors by the liver [1]. Warfarin needs to be used cautiously due to its narrow therapeutic window and dosing is affected by genetic variation, drug interaction, and nutrition [2].

During the use of warfarin, a significant life-threatening complication is haemorrhage. Although rare, spontaneous upper airway hematoma haemorrhage in patients on anticoagulant therapy of varying severity has been reported [3–9]. Most upper airway hematomas were sublingual hematomas (66.57%) followed by retropharyngeal hematomas (27.03%). Of the cases, 48.65% were reported to be managed conservatively while the rest underwent either cricothyrotomy or tracheal intubation [10]. The complications of upper airway hematomas included respiratory compromise, which was seen in almost half of the cases, followed by pulmonary oedema [11], aspiration pneumonia [8], and mild pneumonitis [12]. There was also a reported case of a patient who died due to anoxic brain injury secondary to upper airway hematoma [13].

When using warfarin, the risk of major bleeding within one year of use ranges between 0.5 to 7.0%, and this risk is directly proportional to the warfarin dosage. This haemorrhagic risk increases in patients whose INR was 6 or more [14] and also in elderly patients who were concurrently on nonsteroid anti-inflammatory and methyl-salicylate.

The commonest presentation of sublingual hematoma is hoarseness of voice and painless swelling in the oral cavity or neck. Physical examination may confirm a sublingual swelling. In our patient, a small laceration at her lower jaw was seen, most probably due to trauma during removal of her dentures. This event initially developed a painless anterior neck swelling, which was ignored by the patient. The traumatic injury in the sublingual area however became worst, causing a retropharyngeal and epiglottic hematoma.

Haemorrhage and hematoma of the oral cavity can be fatal. Bleeding and hematoma into the sublingual and submaxillary spaces may also create a pseudo-Ludwig’s phenomenon [5]. With an acute expanding hematoma, the tongue and floor of the mouth may become elevated. This will lead to an airway obstruction.

If diagnosed early and managed promptly, the prognosis will be good, and the haematomas may resolve completely. Once diagnosed, these patients will require prompt airway management, reversal of anticoagulation, as well as close monitoring. Airway management should be performed ideally with awake intubation, while maintaining a spontaneous respiration. However, in a situation where tracheal intubation is not successful, emergency cricothyroidotomy or surgical tracheostomy should be performed for definitive airway stabilization.

In severe sublingual hematoma, anticoagulation should be reversed immediately with Prothrombin Complex Concentrate (PCC) or Fresh Frozen Plasma (FFP), followed by vitamin K. Both oral and intravenous routes for vitamin K sufficiently reverse anticoagulation and result in similar reductions in INR at 24 hours [15]. Although both PCC and FFP can be used, PCC has several advantages over FFP. PCCs have smaller infusion volumes and have an enhanced safety because of viral inactivation [16]. In the treatment of our case, oral warfarin was discontinued and FFP 15ml/kg was given. PCC was not available at our centre.

4. Conclusion

Warfarin-induced submandibular hematoma can cause airway obstruction. In these patients, early definitive airway management is crucial. A rapid medical management is also crucial to reverse the effects of warfarin.

Data Availability

No data were used to support this study.

Conflicts of Interest

The authors declare that there are no conflicts of interest regarding the publication of this paper.

Supplementary Materials

Video 1: air bubbles seen from the posterior side of the engorged epiglottis, which served as a guide for tracheal tube insertion. (Supplementary Materials)

Warfarin: a blood-thinning medicine to treat and prevent blood clots

Dosage and strength

The usual warfarin dose is 10mg a day for the first 2 days, then between 3mg and 9mg a day after that.

Warfarin tablets come in 4 different strengths. The tablets and the boxes they come in are different colours to make it easier for you to take the right dose.

The strengths and colours are:

• 0.5mg – white tablet
• 1mg – brown tablet
• 3mg – blue tablet
• 5mg – pink tablet

Your dose may be made up of a combination of different coloured tablets.

Warfarin also comes as a liquid, where 1ml is equal to a 1mg (brown) tablet.

Warfarin liquid comes with a plastic syringe to help you measure the right amount.

How to take it

It’s very important to take warfarin as your doctor advises. Take it once a day at about the same time.

It’s usual to take warfarin in the evening. This is so that if you need to change the dose after a routine blood test, you can do this the same day rather than waiting until the following morning.

Warfarin does not usually upset your stomach, so you can take it whether you have eaten recently or not.

How long to take it for

If you have had a blood clot in your leg or lungs, you’ll probably take a short course of warfarin for 6 weeks to 6 months.

If you take warfarin to reduce your risk of having a blood clot in future or because you keep getting blood clots, it’s likely your treatment will be for longer than 6 months, maybe even for the rest of your life.

Will my dose go up and down?

Your warfarin dose may change often, especially in the first few weeks of treatment, until your doctor finds the dose that’s right for you.

Why do I have blood tests?

The aim of treatment with warfarin is to thin your blood but not stop it clotting completely. Getting this balance right means your dose of warfarin must be carefully monitored.

You’ll have a regular blood test called the international normalised ratio (INR). It measures how long it takes your blood to clot. The longer your blood takes to clot, the higher the INR.

Most people taking anticoagulants have a ratio of between 2 and 3.5. This means their blood takes 2 to 3.5 times longer to clot than usual.

The dose of warfarin you need depends on your blood test result. If the blood test result has gone up or down, your warfarin dose will be increased or decreased.

You’ll have the blood tests at your GP surgery or local hospital’s anticoagulant clinic.

If your blood test results are stable, you might only need a blood test once every 8 to 12 weeks. If it’s unstable or you have just started on warfarin, you might need to have a blood test every week.

The yellow book and alert card

When you start taking warfarin, you may be given a yellow book about anticoagulants.

This explains your treatment. There’s also a section for you to write down and keep a record of your warfarin dose.

It’s a good idea to take your yellow book with you to all your warfarin appointments.

You’ll also be given an anticoagulant alert card. Carry this with you all the time.

It tells healthcare professionals that you’re taking an anticoagulant. This can be useful for them to know in case of a medical emergency.

If you need any medical or dental treatment, show your anticoagulant alert card to the nurse, doctor or dentist beforehand.

This includes before you have vaccinations and routine sessions with the dental hygienist.

Your doctor may advise you to stop taking warfarin or reduce your dose for a short time before your treatment.

If you have lost your alert card or were not given one, ask your doctor or anticoagulant clinic.

What if I forget to take it?

It’s important to try to remember to take your warfarin on time.

It’s not a problem if you occasionally forget to take a dose at the correct time.

But if you forget often, your blood could be affected – it might become thicker and put you at risk of having a blood clot.

If you miss a dose of warfarin, write it down in your yellow book.

Take the missed dose as soon as you remember.

If you do not remember until the next day, skip the missed dose and take your normal dose at the usual time.

Never take more than 1 dose a day.

If you often forget doses, it may help to set an alarm to remind you.

You could also ask your pharmacist for advice on other ways to help you remember to take your medicine.

If you’re worried, contact your anticoagulant clinic or doctor.

What if I take too much?

If you take an extra dose of warfarin, call your anticoagulant clinic straight away.

You may need to change your next dose of warfarin or have a blood test.

If you take more than 1 extra dose of warfarin, you’re at risk of serious bleeding.

Bruise or Hematoma | Primary Care

Causes of bruise or hematoma

Causes of a bruise

• Accidents or bumps
• Microscopic tears in the blood vessels under the skin in athletic people
• Bleeding disorders — unexplained bleeding that occurs without reason
• Thinner skin due to aging

Causes of a hematoma

Trauma is the primary cause of a hematoma. Trauma can be the result of a car accident, fall, broken bones, gunshot wound or head injury.

Hematomas may also be caused by:

• Aneurysm
• Certain medications
• Viral infections such as rubella, mumps, chickenpox, HIV or hepatitis C
• Orthopedic injuries such as fractures

Risk factors for bruise or hematoma

Risk factors for a bruise

People who have any of the following factors are at higher risk for developing a bruise.

• Vitamin C deficiency
• Bleeding disorders
• Patients who take anticoagulants (blood thinners)

Risk factors for a hematoma

• Older age
• Anticoagulant (blood thinner) usage
• Recent trauma

Symptoms of bruise or hematoma

Symptoms of a bruise

• Dark blue or purple patch of skin that appears within a few hours after injury
• Tenderness on or around the affected area

Symptoms of a hematoma

• Inflammation
• Redness
• Tenderness
• Warmth
• Pain
• Swelling

Diagnosis of bruise or hematoma

Diagnosing a bruise

Most people can self-diagnose a mild bruise after evaluating the signs or symptoms.

If you have a severe bruise and suspect you may have more serious injuries, your doctor may order an x-ray of the area to ensure you do not have broken bones.

If you have frequent bruising, your primary care doctor may order a blood test to check for a bleeding disorder.

Diagnosing a hematoma

If the hematoma symptoms are severe or if it continues to expand over the course of a few days, you should visit your doctor right away. Emergency medicine, urgent care, primary care physicians frequently care for patients with hematomas.

A primary care doctor can diagnose a soft tissue hematoma in a physical exam. If you are experiencing more serious symptoms, your doctor may order any of the following diagnostic tests:

• X-ray — to diagnose bone fractures
• CT scan — to diagnose head injuries
• Ultrasound — for pregnant patients

Treatment for a bruise or a hematoma

Treatment should begin as quickly as possible after injury. First-line therapy is rest, ice, compression and elevation (RICE method). If the injured area is painful, the injury can be treated with OTC medications like Tylenol or Advil.

If you have a hematoma that involves other organs in the body, your treatment will be tailored to your situation.

Subdural Hematoma | Cedars-Sinai

Not what you’re looking for?

What is a subdural hematoma?

A subdural hematoma is a buildup of blood on the surface of the brain. The blood builds
up in a space between the protective layers that surround your brain.

Your brain sits within a bony
skull. Inside your skull and over the brain there are 3 layers called the meninges.
These layers cover and protect the
brain. The outermost covering is just inside the skull. It’s a tough, fibrous layer
called the dura mater, or usually just dura. On the inside of the dura is a layer
called the arachnoid. Closest to the brain is a membrane called the pia. Cerebrospinal
fluid (CSF) fills the space inside the
meninges. CSF also helps cushion your brain.

The dura lines the skull and
surrounds the brain. In a subdural hematoma, the blood seeps between the dura and
the arachnoid layers. It collects inside the
brain’s tough outer lining. This bleeding often comes from a blood vessel that breaks
within the space around the brain. This most often happens because of a head injury.
The
injury can be mild. The blood may press against the brain and damage the tissue.
A
subdural hematoma can be life-threatening.

A subdural hematoma is not
uncommon. It happens in some people who get a severe head injury. Younger men are
most
likely to get these types of injuries. Older adults are at higher risk for a subdural
hematoma, even with mild head injury. This is because the veins surrounding the brain
are more likely to tear. About a third of subdural hematomas happen in older adults.
In
babies, subdural hematomas are often from shaken baby syndrome.

What causes a subdural hematoma?

The most common cause for a
subdural hematoma is head injury. This can be from a car crash, fall, or violent attack.
This sudden impact can strain the blood vessels within the dura, causing them to rip
and
bleed. Sometimes small arteries also break within the subdural space. In some people,
the brain shrinks (often from aging) and the subdural space gets bigger. This can
make
the blood vessels more likely to break. In people 50 and older, subdural hematomas
can
be present for days or weeks. These are called chronic subdural hematoma because the
blood clot changes into liquid. It becomes dark in color.

Possible causes for a subdural
hematoma include:

• Head injury, such as from accidents or
  violence. This is most common in younger people.
• Brain shrinking (atrophy). This is
  more common in older adults.
• Medicines to prevent blood clots, such
  as warfarin, aspirin, and other blood thinners
• Leak of cerebrospinal fluid

Who is at risk for a subdural hematoma?

A subdural hematoma is most often
the result of head injury. So people at risk of car crashes or falls are most at risk
for this problem. You may have a higher risk for subdural hematoma from:

• Head injury, such as from car crashes, falls, or sudden changes in speed
• Playing high-impact sports
• Advanced age. This makes it more
  likely that the brain has shrunk, putting the blood vessels at risk for damage.
• Alcohol abuse
• Previous brain injury
• Using blood-thinning medicine
• Violence, such as shaken baby
  syndrome
• Cerebrospinal fluid leak (rare)
• Blood vessel rupture at a weak or
  bulging spot (cerebral aneurysm) (rare)
• Tumor (rare)
• Bleeding disorders such as hemophilia
  (rare)

What are the symptoms of a subdural hematoma?

A subdural hematoma may cause symptoms right away (acute), or it may slowly grow and
cause symptoms at a later time. You may notice the symptoms weeks after an injury
or blood vessel breaking (chronic).

Symptoms of a subdural hematoma may
include:

• Balance or walking problems
• Confusion
• Dizziness
• Headache
• Nausea or vomiting
• Passing out (losing consciousness)
• Seizures
• Sleepiness
• Speech problems
• Vision problems
• Weakness or numbness that may come and go

How is a subdural hematoma diagnosed?

An acute subdural hematoma is an
emergency. You will need a physical exam, including a check of your reflexes, plus
your
head, eyes, and neck. Doctors usually check for any weakness or signs of brain problems.
You may be asked when you first noticed the symptoms. Your doctor may ask you to do
some
simple things, such as touching your finger to your nose.

Doctors generally do a CT scan or a
MRI of your head to look for signs of bleeding. It is very important to find the site
of
the bleeding. You may need to have one or more tests, such as:

• Blood tests to look for bleeding
  disorders and measure clotting function
• Blood tests to look for other possible
  causes of your symptoms
• More imaging of your blood vessels (CT
  angiography) to find underlying problems

Diagnosis of subdural hematomas often occurs in emergency rooms.

How is a subdural hematoma treated?

Doctors often treat subdural
hematomas with surgery to ease pressure on the brain. Your doctor may use a variety
of
surgeries to treat the hematoma. These include:

• Cutting a flap of skull open to remove the blood (craniotomy)
• Drilling a hole in the skull to allow the blood to drain (burr hole)

If your subdural hematoma is small,
doctors might watch it closely instead of doing surgery right away. In this case,
you
will likely stay in an intensive care unit. You may need:

• A sensor inside your head to measure
  your intracranial pressure
• Medicines to control symptoms
• Repeated CT scans to watch the
  hematoma
• A stop to blood-thinning medicines
  such as warfarin if you normally take them
• Vitamin K therapy. This can reverse
  the effects of some blood-thinning medicines.

Can a subdural hematoma be prevented?

Protecting yourself from head
injuries may help prevent subdural hematomas. It is important to wear a helmet when
riding a motorcycle, scooter, bicycle, or skateboard. Wearing seatbelts when in a
car
and using safety equipment in dangerous situations may help protect your head from
injury. You can take steps to prevent falls.

When should I call my healthcare provider?

A subdural hematoma is an
emergency. If you or someone else has had a head injury and has the symptoms listed
above, you should call 911
 or go to the
nearest emergency room.

Key points about subdural hematomas

• A subdural hematoma is a collection of blood that forms on the
  surface of the brain. The blood may press against the brain and damage the tissue.
  A
  subdural hematoma can be life-threatening.
• A chronic subdural hematoma may happen
  in older people after a minor head injury.
• A subdural hematoma may happen after a
  severe head injury.
• Doctors often treat subdural hematomas
  with surgery to ease pressure on the brain.
• If you have a subdural hematoma, you
  need emergency treatment.
• Symptoms may happen right away or
  develop over weeks.

Next steps

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

• Know the reason for your visit and what you want to happen.
• Before your visit, write down questions you want answered.
• Bring someone with you to help you ask questions and remember what your healthcare
  provider tells you.
• At the visit, write down the name of a new diagnosis, and any new medicines, treatments,
  or tests. Also write down any new instructions your healthcare provider gives you.
• Know why a new medicine or treatment is prescribed, and how it will help you. Also
  know what the side effects are.
• Ask if your condition can be treated in other ways.
• Know why a test or procedure is recommended and what the results could mean.
• Know what to expect if you do not take the medicine or have the test or procedure.
• If you have a follow-up appointment, write down the date, time, and purpose for that
  visit.
• Know how you can contact your healthcare provider if you have questions.

Medical Reviewer: Luc Jasmin MD

Medical Reviewer: Anne Fetterman RN BSN

Medical Reviewer: Raymond Kent Turley BSN MSN RN

© 2000-2021 The StayWell Company, LLC. All rights reserved. This information is not intended as a substitute for professional medical care. Always follow your healthcare professional’s instructions.

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Continued Warfarin Better Than Bridging Therapy for Pacemaker or Defibrillator Surgery – POEMs

Am Fam Physician. 2013 Sep 15;88(6):403.

Clinical Question

For patients who are currently taking warfarin (Coumadin) and undergoing the insertion of a pacemaker or defibrillator, should warfarin be continued or should patients be bridged with heparin?

Bottom Line

This is the best and largest single trial comparing continued warfarin with a bridging strategy. Patients with an annual risk of thromboembolic events of 5% or more undergoing pacemaker or defibrillator surgery who continued to use warfarin had fewer device-pocket hematomas than patients who received bridging therapy with heparin. This result is consistent with the results of previous observational studies [Circulation. 2012;126(13):1630–1639] that found that bridging actually worsens outcomes. One theory is that the surgeons performing the implantation in a patient receiving anticoagulants were better able to identify potential bleeding complications intraoperatively—what the authors call an “anticoagulant stress test.” It’s refreshing that the simpler, less expensive, and far less complex strategy is also the better one. (Level of Evidence = 1b)

Synopsis

There have been few clinical trials to guide decisions about anticoagulation management during surgical procedures. This is one of the first to rigorously address this issue. The researchers identified 681 patients with at least a 5% annual risk of thromboembolism who were taking warfarin and who were scheduled to have a pacemaker or defibrillator implanted. Their mean age was 71 years, 73% were male, and most had atrial fibrillation or flutter as the indication for anticoagulation. The patients were randomized, with appropriate concealment of allocation, to continue their usual management with warfarin or to receive bridging heparin. Patients in the bridging group received their final dose of warfarin at least five days before the procedure, and received full-dose low-molecular-weight heparin (Lovenox) or unfractionated heparin from that point until 24 hours before the procedure (for the low-molecular-weight heparin) or four hours before the procedure (for the unfractionated heparin). The heparin and warfarin were restarted 24 hours after the procedure, and heparin was discontinued once a therapeutic international normalized ratio (INR) was achieved.

The patients were not masked, but the members of the care team evaluating each patient for hematoma were masked to group assignment. Groups were balanced at the beginning of the study, analysis was by intention to treat, and follow-up was excellent. The primary outcome was occurrence of a device-pocket hematoma that necessitated further surgery, a longer hospitalization, or interruption of anticoagulation. The study was terminated prematurely because this outcome occurred in 3.5% of patients in the continued warfarin group and in 16% of patients in the heparin-bridging group (relative risk = 0.19; 95% confidence interval, 0.1 to 0.36; absolute risk increase = 12.5%; number needed to treat to harm = 8). Two patients in the continued warfarin group had embolic events, but both had unintentionally subtherapeutic INR values of 1.0 and 1.2.

Reference

Birnie DH,

Healey JS,

Wells GA,

et al.;

BRUISE CONTROL Investigators.

Pacemaker or defibrillator surgery without interruption of anticoagulation. N Engl J Med.
2013;
368(
22):
2084–
2093.

Study design: Randomized controlled trial (single-blinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (any location) with outpatient follow-up

Spontaneous rupture and hematoma of the sartorius muscle secondary to rivaroxaban therapy | Journal of Surgical Case Reports

Abstract

Spontaneous muscular hematomas are quite rare as they occur mush less frequently than intracranial hematomas and gastrointestinal bleeding in patients under oral anticoagulant therapy. Coumarins, such as warfarin or acitrom, are the most widely prescribed oral anticoagulants agents and have been associated more with the development of hematomas than direct factor X inhibitors, such as rivaroxaban [ 1]. Few reports have linked oral anticoagulation therapy with the development of muscular hematomas; however, clinical cases regarding the involvement of the sartorius muscle remain limited. Patients with advanced age, under oral anticoagulant therapy with pain and ecchymosis in the thigh region, should undergo radiological evaluation utilizing ultrasonography, computed tomography or magnetic resonance imaging to establish an accurate diagnosis. The following case consists of a patient that while resting presented with a spontaneous rupture and hematoma of the sartorius muscle secondary to rivaroxaban use. During follow-up, the patient recovered completely.

INTRODUCTION

The rate of major extra cranial bleeding in patients under oral anticoagulant therapy is between 0.4 and 2% per year [2]. Globally, warfarin is the most frequently prescribed oral anticoagulant and is associated with a higher risk of bleeding compared with the direct factor Xa inhibitors [3]. In the majority of cases, spontaneous muscular hematomas are attributed to oral anticoagulation therapy. Therefore, a high degree of suspicion is necessary when patients present with pain, edema and ecchymosis in a muscle region. Diagnostic imaging studies are compulsory to establish an adequate diagnosis and to decide between conservative and surgical treatment [4]. In few cases, thigh muscles have been affected. However, reports regarding sartorius muscle involvement remain limited. The present case consists of a patient that while resting developed a non-traumatic rupture and hematoma of the sartorius muscle associated to rivaroxaban therapy.

CASE PRESENTATION

The clinical case consisted of a 79-year-old male patient with a medical history of atrial fibrillation and pulmonary embolism diagnosed 2 years ago. Among the prescribed medications, rivaroxaban was given as an anticoagulant therapy. The patient was lying in bed when a sudden onset of a sprain-like pain appeared on his right thigh region. He had difficulty walking and observed the progression of a large ecchymosis along the thigh, extending from the greater trochanter of the femur to above the patella. Later as the clinical manifestations worsened, the patient arrived at the emergency department. At the hospital, the treating physician noticed edema, ecchymosis and pain confined to the thigh region; therefore, ordered laboratory studies, such as prothrombin time, international normalized ratio and hemoglobin were all within the normal range for the patient’s age and comorbidities. The doctor solicited a magnetic resonance imaging (MRI) study to evaluate the thigh region where a rupture and hematoma regarding the sartorius muscle was evident. The MRI displayed a hyperintense area representing blood collection and discontinuity in the trajectory of the sartorius muscle (Figs 1–3). The hematoma was large in volume, hence surgical drainage was performed. After the procedure, the patient’s pain diminished considerably and was ordered to rest. Posteriorly, the patient began rehabilitation exercises and cooperated with follow-up dates to test progression. The patient attended a follow-up appointment after 6 months of initial presentation where a positive clinical outcome and enhanced walking capacity was observed.

Figure 1

MRI axial view of right thigh region showing hematoma.

Figure 1

MRI axial view of right thigh region showing hematoma.

Figure 2

MRI sagittal view manifesting hematoma in right thigh region.

Figure 2

MRI sagittal view manifesting hematoma in right thigh region.

Figure 3

MRI coronal view displaying hematoma and rupture of sartorius muscle.

Figure 3

MRI coronal view displaying hematoma and rupture of sartorius muscle.

DISCUSSION

Since its discovery in 1941, warfarin has been the most commonly prescribed oral anticoagulant agent. Although this coumarin is associated with a reduction of stroke risk, many setbacks have been identified such as unpredictable pharmacokinetics and pharmacodynamics, a slow onset and offset of action, a narrow therapeutic window and variable dose response among each patient [5]. Additionally, the risk of major bleeding is greater with warfarin than non-vitamin K oral anticoagulants (NOACs). Rivaroxaban is a direct factor Xa inhibitor that has the similar efficacy in stroke prevention but a lower incidence in intracranial bleeding than coumarins. However, incidence of gastrointestinal bleeding is slightly higher with rivaroxaban compared to warfarin. Evidently, these drugs provoke an imbalance in the physiology of coagulation factors; therefore, laboratory monitoring of bleeding is necessary [3, 5]. However, in rare instances, bleeding can occur when the patient’s international normalized ratio (INR) and prothrombin time values lie within the therapeutic range such as the patient in the present case.

Rivaroxaban is considered safe when INR values lie between 1.2 and 2.5, nonetheless with a 7% major bleeding risk when the value exceeds 2.5. Intracranial bleeding can occur in certain patients especially when INR values lie above 3; however, limited cases have been reported when plasma levels, INR and prothrombin time are normal [6]. Ideally, NOAC plasma concentration levels can be identified utilizing high-performance liquid chromatography-tandem mass spectroscopy, but such testing is limited to reference laboratories and is unfeasible for routine clinical use. When NOAC concentration levels exceed ideal values, there is an increased risk of bleeding particularly from either an intracranial or gastrointestinal source [6, 7]. Nonetheless, in some instances, muscular hematomas have been reported in patients under anticoagulant treatment. Çinar et al. described four cases of spontaneous muscular hematomas. However, they were attributed to warfarin and affected the psoas, quadriceps, pectoral and rectus abdominis muscles [8]. To the best of our knowledge, no report has described a non-traumatic rupture and hematoma localized in the sartorius muscle such as this case.

Thigh hematomas initially present with localized edema, pain and ecchymosis along the affected region. In these cases, radiological imaging using ultrasonography, computed tomography or magnetic resonance imaging is necessary to establish an accurate diagnosis especially in patients taking oral anticoagulant medications. Radiological modalities vary in affordability and image clarity. Although ultrasonography is the most economical, interpretation is user dependent. Small hematomas are treated in a conservative fashion [4, 9]. Conservative treatment consists of rest, ice application, local compression and limb elevation. Nevertheless, large volume of hemorrhages may require surgical drainage and hemoglobin testing to justify the need for blood transfusion. Following initial management, the patient must undergo rehabilitation to optimize range of motion and progressively diminish pain [9].

CONCLUSION

Spontaneous muscular hematomas in the thigh region are infrequent and are attributed in the majority of cases to oral anticoagulant therapy. This diagnosis must be considered in patients who manifest pain, ecchymosis and edema in the thigh region. Although rivaroxaban treatment is considered safer, treating physicians ought to consider the possibility. In this particular case, the patient was lying in bed and spontaneously developed a rupture and hematoma of the sartorius muscle secondary to rivaroxaban use, which is rather rare since most cases are chiefly linked to warfarin. Clinicians are advised to acknowledge this unusual bleeding site in patients under anticoagulation treatment regardless of drug safety and less variability of response to prevent negative effects in the patient’s quality of life.

CONFLICT OF INTEREST STATEMENT

None declared.

References

1.

Vaddera

S

,

Shafi

L

,

Reddy

RG

,

Gayatri

S

,

Krishna

NV

.

Thigh hematoma following oral anticoagulant therapy: a case report

.

Int J Contemp Med Res

2016

;

3

:

388

–

90

.2.

Hylek

E

.

Complications of oral anticoagulant therapy: bleeding and nonbleeding, rates and risk factors

.

Semin Vasc Med

2003

;

03

:

271

–

8

. doi: .3.

Fanaroff

AC

,

Ohman

EM

.

Non–vitamin K antagonist oral anticoagulants in the treatment of atrial fibrillation

.

Annu Rev Med

2019

;

70

:

61

–

75

. doi: .4.

Wada

Y

,

Yanagihara

C

,

Nishimura

Y

.

Bilateral Iliopsoas hematomas complicating anticoagulant therapy

.

Intern Med (Tokyo, Japan)

2005

;

44

:

641

–

3

. doi: .5.

Perzborn

E

,

Roehrig

S

,

Straub

A

,

Kubitza

D

,

Misselwitz

F

.

The discovery and development of rivaroxaban, an oral, direct factor Xa inhibitor

.

Nat Rev Drug Discov

2010

;

10

:

61

–

75

. doi: .6.

Levy

JH

,

Douketis

J

,

Weitz

JI

.

Reversal agents for non-vitamin K antagonist oral anticoagulants

.

Nat Rev Cardiol

2018

;

15

:

273

–

81

. doi: .7.

Eikelboom

JW

,

Quinlan

DJ

,

Hirsh

J

,

Connolly

SJ

,

Weitz

JI

.

Laboratory monitoring of non–vitamin K antagonist oral anticoagulant use in patients with atrial fibrillation

.

JAMA Cardiol

2017

;

2

:

566

. doi: .8.

Çınar

N

,

Şahin

Ş

,

Karaoğlan

A

,

Karşıdağ

S

.

Intramuscular hematomas caused by anticoagulant therapy: is advanced age a risk factor?

Arch Neuropsychiatry

2011

;

48

:

1

–

1

. doi: .9.

Järvinen

TA

,

Järvinen

TL

,

Kääriäinen

M

,

Äärimaa

V

,

Vaittinen

S

,

Kalimo

H

, et al. 

Muscle injuries: optimising recovery

.

Best Pract Res Clin Rheumatol

2007

;

21

:

317

–

31

. doi: .

Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author(s) 2020.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

(PDF) Warfarin-associated epidural hematoma with spinal cord compression

87

JOURNAL OF NEUROLOGY AND PSYCHIATRY, 9, 2016

15. Vandermeulen EP, Van Aken H, Vermylen J. Anticoagulants and spinal epidi-

anhesia. Anesth Analg. 1994; 79: 1165-1177.

doi: 10.1213 / 00000539-199412000-00024

16. Moen V, Dahlgren N, Irestedt L. Severe neurological complications after

central neuraxial blockades in Sweden 1990-1999.Anesthesiology.

2004; 101: 950-959.

doi: 10.1097 / 00000542-200410000-00021

17. Gundry CR, Heithoff KB. Epidural hematoma of the lumbar spine: 18 sur-

gically confirmed cases. Radiology. 1993; 187: 427-431.

doi: 10.1148 / radiology.187.2.8475285

18. Kickman CA, Zabramski JM, Sonntag VK, Coons S. Myelopathy due to

epidural varicose veins of the cervicothoracic junction. Case report. J Neuro-

surg.1988; 6 (69): 940-941.

doi: 10.3171 / jns.1988.69.6.0940

19. Zozulya Yu.A., Slynko E.I. Spinal epidural vascular

malformations. Ukrainian neurosurgical journal. 2000; 2.

20. K’Angelo VK, Bizzozero L, Talamonti G, Ferrara M, Colombo N. Value of

magnetic resonance imaging in spontaneous extradural spinal hematoma

due to vascular malformation. Case report. Surg Neurol. 1990; 34: 343-344.

doi: 10.1016 / 0090-3019 (90)

-e

21. Groen RJ. The spontaneous spinal epidural hematoma: a clinical and ana-

tomical study with correlations to the morphology of the internal vertebral ve-

nous plexus. Amsterdam: Thesis Publishers. 1997.

22. Alderman DB. Extradural spinal cord hematoma: report of a case due to

dicumarol and review of the literature. N Engl J Med. 1956; 255: 839-884.

doi: 10.1056 / nejm195611012551802

23.Piotrowski W, Kroger M, Tornow K. Das spinale epidurale Haematom.

Nervenarzt. 1979; 50: 426-431.

24. Lawton MT, Porter RW, Heiserma Dickman CA. Surgical management of

spinal epidural haematoma: relationship surgical timing and neurological

outcome. J Neurosurg. 1985; 83: 1-7.

doi: 10.3171 / jns. 1995.83.1.0001

25. Liao CC, Lee ST, Hsu WC, Chen LR, Lui TN, Lee SC. Experience in the

surgical management of spontaneous spinal epidural hematoma.J Neuro-

surg. 2004; 100: 38-45.

doi: 10.3171 / spi. 2004.100.1.0038

26. Fujiwara H, Oki K, Momoshima S, Kuribayashi S. PROPELLER diffu-

sion-weighted magnetic resonance imaging of acute spinal epidural hema-

toma. Acta Radiol. 2005; 46 (5): 539-542.

doi: 10.1080 / 02841850510021553

27. Holtas S, Heiling M, Lonntoft M. Spontaneous spinal epidural hematoma:

findings at MR imaging and clinical correlation.Radiology. 1996; 199 (2): 409-

413.

doi: 10.1148 / radiology.199.2.8668786

28. Lovblad KO, Baumgartner RW, Zambaz BD, Remonda L., Ozdoba C.,

Schroth G. Nontraumatic spinal epidural hematomas. MR features. Acta

Radiol. 1997; 38 (1): 8-13.

doi: 10.1080 / 02841859709171234

29. Shah LM, Salzman KL. Imaging of spinal metastatic disease. Int J Surg

Oncol. 2011; 769753.

doi: 10.1155 / 2011/769753

30.Chamberlain MC, Tredway TL. Adult primary intradural spinal cord tu-

mors: a review. Curr Neurol Neurosci Rep. 2011; 11 (3): 320-328.

doi: 10.1007 / s11910-011-0190-2

31. Patel D, Baron EM, Enochs WS, Ruth C, Harrop JS, Vaccaro AR. Spinal

epidural abscess mimicking lymphoma: a case report. Orthopedics.

2008; 31 (4): 402.

doi: 10.3928 / 01477447-20080401-29

32. Mackenzie AR, Laing RB, Smith CC. Spinal epidural abscess: the impor-

tance of early diagnosis and treatment.J Neurol Neurosurg Psychiatry.

1998; 65: 209-212.

doi: 10.1136 / jnnp. 65.2.209

33. Hodler J, von Schulthess GK, Zollikofer ChL. Diseases of the brain, head

and neck, spine diagnostic imaging and interventional techniques. Springer-

Verlag Italia. 2008; 287.

doi: 10.1007 / 978-88-470-0840-3_43

34. Parkinson JF, Sekhon LH. Spinal epidural abscess: appearance on mag-

netic resonance imaging as a guide to surgical management.Report of five

cases. Neurosurg Focus. 2004; 17 (6): 12.

doi: 10.3171 / foc.2004.17.6.12

35. Matsui H, Imagama S, Ito Z, Ando K, Hirano K, Tauchi R, Muramoto A,

Matsumoto T, Ishiguro N. Chronic spontaneous lumbar epidural hemato-

ma simulating extradural spinal tumor: a case report. Nagoya J Med Sci.

2014; 76 (12): 195-201.

36. Yumashev G.S., Furman M.E. Osteocondritis of the spine. M .: Medicine –

on; 1984.

37. P.V. Veselovsky Practical vertebral neurology and manual therapy

rapia. Riga. 1991.

38. Zateishchikov DA, Zotova IV, Dankovtseva E. et al. Thrombosis and anti-

thrombotic therapy for arrhythmias. M .: Practice; 2011.

39. Bokareva I.N., Popova L.V., Kozlova T.V. Thrombosis and antithrombotic therapy in clinical practice. Moscow: OOO Medical

Information Agency. 2009.

40. Padrini R, Ferrari M, Carnes M.Pharmacogenetics. N Engl J Med.

2003; 348: 2041-2043.

41. Kirkwood TB. Calibration of reference thromboplastins and standardisa-

tion of the prothrombin time ratio. Thrombosis and Haemostasis.

1983; 49 (3): 238-244.

42. Clinical guidelines for the management, diagnosis and treatment of valve-

heart defects. M .: Publishing house of the NTSSSH im. A.N. Bakulaeva RAMS;

2009.

43. Bonow RO. Focused update incorporated into the ACC / AHA 2006 Guide-

lines for the management of patients with valvular heart disease: A report of

the American College of Cardiology / American Heart Association Task

Force on Practice Guidelines (Writing committee to revise the 1998 Guide-

lines for the management of patients with valvular heart disease).Circula-

tion. 2008; 118 (15).

doi: 10.1161 / circulationaha.108.1

44. Hylek MPH, Go AS, Yuchiao Chang. Effect of Intensity of Oral Anticoagu-

lation on Stroke Severity and Mortality in Atrial Fibrillation. NEJM.

2003; 349: 1019-1026.

doi: 10.1056 / nejmoa022913

45. Levine MN, Raskob G, Landefeld S, Kearon C. Hemorrhagic complication

of anticoagulant treatment. Chest. 2001; 19 (1): 108-121.

doi: 10.1378 / chest.119.1_suppl.108s

46. Hirsh AJ, Hylek EM. Pharmacology and Management of the vitamin K an-

tagonists. American College of Chest Physicians Evidence — Based Clinical

Practice Guidelines (8th Edition). Chest. 2008; 133: 160-198.

doi: 10.1378 / chest.08-0670

47. Zabolotskikh I.B., Kirov M.Yu., Bozhkova S.A., Bulanov A.Yu., Vor-

Bieva N.A., Grigoriev E.V., Gritsan A.I., Kurapeev I.S., Lebedin-

sky K.M., Lomivorotov V.V., Ovechkin A.M., Potievskaya V.I.,

Sinkov S.V., Subbotin V.V., Shulutko E.M. Perioperative care –

treatment of patients receiving long-term antithrombotic therapy –

pia. Clinical guidelines. Anesthesiology and Reanimatology.

2014; 4: 4-14.

48. Aguilar MI, Hart RG, Kase CS. Treatment of warfarin associated intracere-

bral hemorrhage: literature review and expert opinion. Mayo Clin Proc.

2007; 82: 82-92.

doi: 10.1016 / s0025-6196 (11) 60970-1

49. Kropacheva E.S., Panchenko E.P. Fundamentals of tamin K antagonist therapy

for medical practitioners. Russian medical journal.

2009; 8: 507-513.

50. Hussenbocus SM, Wilby MJ, Cain C, Hall D. Spontaneous spinal epidural

hematoma: a case report and literature review. J Emerg Med. 2012; 42: 31-34.

doi: 10.1016 / j.jemermed. 2008.08.008

51. Hentschel SJ, Woolfender AR, Fairholm DJ.Resolution of spontaneous

spinal epidural hematoma without surgery. A report of two cases. Spine.

2001; 26 (22): 525-527.

doi: 10.1097 / 00007632-200111150-00025

WARFARIN ASSOCIATED EPIDURAL HEMATOMA

Warfarin drug interactions with other drugs (compatibility) | Vidal.ru

Investigation of the hemostasis system (coagulogram) in the diagnostic center. Vytnova D.I.

Value of the analysis: coagulogram (Latin coagulatio coagulation, thickening + Greek, gramma line, image) or hemostasiogram – a complex complex analysis.The doctor assesses not so much each specific indicator separately, but the whole picture of blood coagulation.

Blood sampling

Food intake, including juice, tea, coffee, alcohol, is not allowed within 8 hours (preferably 12) before the test. You can drink water. Blood sampling for a hemostasiogram is carried out in special tubes with a blue cap containing sodium citrate. Sodium citrate binds calcium ions and prevents blood clotting. Blood must be drawn exactly to the mark on the tube.If the blood-citrate ratio is violated, the interpretation of the tests is difficult. After sampling, the blood is thoroughly and carefully mixed with citrate without sudden shaking. When taking a hemostasiogram against the background or after taking medications that affect blood coagulation, they must be indicated in the direction form.

Coagulogram tests

APTV

APTT (activated partial thromboplastin time). Test for the internal blood coagulation pathway.Three vitamin K-dependent factors (II, IX, X), factor XII, high molecular weight kininogen (HMC), precallikrein (PC), as well as antihemophilic globulins A (factor VIII: C), B (factor X) and C (factor XI). The activation of the internal pathway in the body occurs when the vascular wall is damaged, contact with a foreign surface, with an excess of adrenaline, biogenic amines, circulating immune complexes, etc. dr.).

Indications for examination:

• Screening test of the state of the coagulation system.
• Investigation of blood coagulation pathology.
• Control of hemostasis in heparin treatment.
• Diagnosis of hemophilia.
• Diagnosis of antiphospholipid syndrome.

Clinical Interpretation

Shortening of the APTT is a sign of thrombophilia or disseminated intravascular coagulation syndrome. Prolongation of APTT: DIC, decreased synthesis of coagulation factors in liver diseases, massive blood transfusions, administration of heparin (lengthening of APTT by 1.5-2 times), deficiency of internal pathway factors, deficiency of vitamin K, presence of coagulation inhibitors, presence of lupus anticoagulant (VA), the presence of hemophilia.

Prothrombin test (PT)

PT is a test for the external (fast) mechanism of hemocoagulation. Vitamin K-dependent factors VII, X, factor V, and tissue factor (TF) or tissue thromboplastin, which triggers the blood coagulation reaction, are involved in blood coagulation along the external pathway. Under physiological conditions, TF enters the bloodstream from damaged or destroyed cells, including leukocytes, macrophages, and tumor cells, and activates the blood coagulation process. A decrease in activity is observed with a lack of blood clotting factors due to a natural or drug-induced decrease in synthesis.

The protorombin test in the coagulogram is expressed by two indicators:

• Activity of prothrombin complex factors according to Quick in%.

  This is the internationally accepted way of expressing PT. The calculation is carried out according to the calibration graph plotted when diluting the donor (control) plasma. It does not correspond to the prothrombin index (PTI) adopted only in Russia.

  Indication for examination:

  • Screening test for the study of the blood coagulation system.
  • Investigation of blood coagulation pathology.
  • Control of hemostasis during treatment with indirect anticoagulants.
  • Assessment of synthesis of prothrombin complex factors in the liver.

  Clinical Interpretation:

  Increased activity (% increase) – a tendency to thrombophilia.

  Decrease in activity (decrease%):

  • Hereditary or acquired deficiency of I, II, V, VII and X factors.
  • Idiopathic familial hypoprothrombinemia.
  • Acquired and hereditary hypofibrinogenemia.
  • Vitamin K deficiency in the diet (factors II, VII, IX and X are formed in hepatocytes in the presence of vitamin K).
  • Maternal vitamin K deficiency (hemorrhagic diathesis in a newborn).
  • Taking medications – vitamin K antagonists (indirect anticoagulants – warfarin, etc.), and drugs that enhance their effect: anabolic steroids, clofibrate, glucagon, thyroxine, indomethacin, neomycin, oxyphenbutazone, salicylates; heparin, urokinase, etc.).

• INR (International Normalized Ratio).

  Used only for treatment with indirect anticoagulants (warfarin, etc.). Not used for screening and assessing liver function.

  Optimal INR limits to be achieved during treatment with indirect anticoagulants depend on therapeutic goals and are determined by the attending physician.

  INR and prothrombin according to Quick correlate negatively – a decrease in prothrombin according to Quick corresponds to an increase in INR.

  When using warfarin, the following rules are recommended:

  • Use warfarin according to the expiration date.
  • Limit vitamin K intake while taking warfarin.
  • Move warfarin away from food intake, since the drug is absorbed by food.
  • Remember that a number of drugs inhibit the action of the drug: barbiturates, corticosteroids, oral contraceptives, meprobamate, etc.

Thrombin time

Thrombin time is the period during which the conversion of fibrinogen to fibrin in citrated plasma occurs after the addition of thrombin to it.The rate of formation of a fibrin clot depends mainly on the amount and functional value of fibrinogen and the presence of anticoagulants in the blood. End-stage blood clotting test.

Indications for the purpose of the study.

• Screening test for the study of the blood coagulation system.
• Determination of fibrinogen deficiency or defectiveness.
• Assessment of the patient’s condition with disseminated intravascular coagulation (DIC syndrome).
• Decreased synthetic liver function.
• Revealing the presence of secondary anticoagulants in the blood – products of fibrin / fibrinogen degradation (FDP).

Clinical interpretation.

Shortening – tendency to thrombophilia, risk of thrombosis.

Elongation: hypo- and dysfibrinogenemia, the presence of physiological (heparin) and pathological (PDP, monoclonal antibodies) thrombin inhibitors, paraproteinemia, uremia, sometimes lupus anticoagulants (VA).

Fibrinogen

Fibrinogen – according to the international nomenclature, factor I (first) of the blood coagulation system. It is produced by the liver and enters the bloodstream. Under the action of thrombin, soluble fibrinogen is converted into insoluble fibrin, which forms the basis of the clot. Fibrin formation goes through several stages (formation of fibrin monomers, polymerization, clot stabilization).

Fibrinogen is a protein of the acute phase of inflammation, therefore it increases during inflammatory and necrotic processes, affects the ESR value (with an increase in fibrinogen concentration, the erythrocyte sedimentation rate increases).An increase in plasma fibrinogen concentration increases blood viscosity and correlates with an increased risk of thrombotic complications of cardiovascular diseases. During pregnancy, there is a physiological increase in the content of blood plasma fibrinogen.

Indications for the purpose of the analysis:

• Blood coagulation pathology.
• Preoperative examination.
• Examination during pregnancy.
• Presence of cardiovascular pathology.

Clinical interpretation.

Increase: inflammation, necrosis, smoking, kidney disease, collagenosis, neoplasms, atherosclerosis, administration of estrogens (including oral contraceptives), pregnancy, etc.

Decrease: congenital deficiency, DIC, hepatocellular failure, acute fibrinolysis, leukemia, infectious mononucleosis, pregnancy toxicosis, snake venoms, the introduction of certain drugs (reptilase, fibrates, phenobarbital, anabolic hormones, androgens, valpro.) and fibrinolytics (streptokinase, urokinase, actilyse, etc.).

Antithrombin III (AT III)

Antithrombin III – the main enzyme of the anticoagulant system of the blood, which accounts for up to 75% of anticoagulant activity. It is a glycoprotein that is synthesized in liver cells. Without heparin, thrombin inactivation by antithrombin III proceeds slowly. In the presence of heparin, the inactivation process unfolds very quickly. Therefore, AT III is called the plasma heparin cofactor.In the case of a significant decrease in the level of AT III, heparin has almost no anticoagulant effect. When the level of AT III in plasma is below 60%, the risk of thrombosis increases sharply.

Indications for use.

• Hereditary AT III deficiency.
• Prophylactic treatment with heparin and for disseminated intravascular coagulation.
• Surgical interventions.
• Pregnancy and childbirth.

Clinical interpretation.

Level increase: inflammatory processes; acute hepatitis; cholestasis; vitamin K deficiency; taking warfarin, acute pancreatitis; menstruation; taking anabolic steroids.

Decrease in the level: impaired synthesis in the liver, rapid consumption with the introduction of heparin in high doses, massive thrombin formation (DIC syndrome), congenital deficiency, treatment with L-asparaginase of late gestosis, taking oral contraceptives, 3 trimester of pregnancy.

Fibrinolytic activity (CPF)

Fibrinolytic activity is the rate of dissolution of a fibrin clot by plasmin and other fibrinolytics contained in blood plasma.When determining fibrinolysis by the traditional euglobulin method, the test in a healthy person lasts 3-5 hours, which is incompatible with modern requirements for laboratory research. Therefore, as a test for assessing the rate of fibrin dissolution, domestic manufacturers proposed the so-called XIIa-dependent or Hageman-dependent fibrinolysis (factor XII is the Hageman factor). It takes place when the contact phase is activated by kaolin and in a healthy person it lasts only 4-12 minutes. The method is basic, as it is sensitive to various pathologies in plasma proteolytic systems.With disseminated intravascular coagulation syndrome, a natural suppression of this type of fibrinolysis begins already at stage 1. The test can also be used to assess the effectiveness of thrombolytic therapy.

Clinical interpretation.

Activation of fibrinolysis (shortening of the clot dissolution time) is quite rare and is usually associated with a decrease in the level of fibrinogen or an increase in the content of plasminogen and its activators (pancreatitis, cancer, shock, liver cirrhosis, pregnancy pathology, terminal conditions, etc.).).

Inhibition of fibrinolysis (prolongation of the clot dissolution time) is observed with hyperfibrinogenemia, congenital decrease and defect of plasminogen, heparin therapy, deficiency of plasminogen and its factors (recurrent venous thrombosis, systemic vasculitis, sepsis, nephrotic syndrome, decreased liver synthesis) the activity of the plasma kallikrein-kinin system.

Assessment of the level of thrombinemia (activation of the intravascular coagulation system)

In a healthy person, fibrinogen is predominantly present in the blood.The remaining intermediate products of the conversion of fibrinogen to fibrin are found in minimal amounts. In a number of forms of pathology characterized by intravascular coagulation of blood (DIC, thrombosis, thrombophilia) under the influence of free thrombin, there is a constant process of transformation of fibrinogen into fibrin and the accumulation of fibrin-monomeric complexes.

Activation of fibrinolysis is accompanied by the formation of fibrin / fibrinogen degradation products (PDP), which interact with fibrin monomers, increasing the amount of soluble fibrin monomer complexes (RFMK) .

Specific products of fibrin degradation under the action of plasmin and other fibrinolytics are D-dimers . Their concentration in the blood is proportional to the activity of fibrinolysis and the amount of lysed fibrin.

Laboratory tests used

RFMK

The test allows you to quantify the level of soluble plasma fibrin, or, in other words, the level of thrombinemia. An increase in the amount of RFMK is observed with thrombosis, thrombophilia, in late pregnancy in accordance with an increase in the content of fibrinogen.The test can also be used to assess the effectiveness and sufficiency of anticoagulant therapy based on its final result – the elimination of thrombinemia (the values ​​obtained are within the reference values).

Ethanol test

With an increase in the level of thrombinemia and the presence of fibrin-monomer complexes with fibrinolysis products and fibrinogen in the studied plasma, a jelly-like clot is formed under the influence of ethanol (positive result, 1). Correlates with RFMK. In a healthy person, a clot does not form (test negative, 0).

D-dimers

An increased level of D-dimer is found in numerous conditions associated with the activation of coagulation (disseminated intravascular coagulation syndrome, deep vein thrombosis, pulmonary embolism, massive tissue damage or surgery, heart failure, infections, inflammation, neoplastic conditions).

Despite the limited specificity of the test (about 50%), the determination of the D-dimer has advantages over the measurement of other markers of coagulation and fibrinolysis, since the D-dimer is formed only from the end product of the conversion of fibrinogen to fibrin – insoluble fibrin, that is, it is thrombus lysis product.During primary fibrinolysis and dysfibrinogenemia, the level of D-dimer does not change.

The concentration of D-dimer in the blood is influenced by such factors as the size of the thrombus, the time from the onset of clinical manifestations to the appointment of anticoagulant therapy, etc. While taking anticoagulants, the level of D-dimer gradually decreases, and thrombolytic therapy causes an increase in the level of D-dimer.

The test is most characterized by a negative diagnostic significance (about 100%), that is, a negative result with a high degree of probability makes it possible to exclude the diagnosis of thrombosis.

In pregnant women, starting from the early stages of pregnancy, the level of D-dimer in the blood gradually rises. By the end of the gestation period, its values ​​can be 3-4 times higher than the initial level. Significantly higher D-dimer indices are observed in women with complicated pregnancy (with gestosis, preeclampsia), as well as in pregnant women with diabetes and kidney disease.

An increase in the level of D-dimer was found in persons over 80 years of age.

Indications for the purpose of the analysis.

• Diagnosis of thrombotic conditions. Deep vein thrombosis (exclusion test). Pulmonary embolism (PE).
• Disseminated intravascular coagulation syndrome (DIC).
• Complicated pregnancy.
• Monitoring of thrombolytic therapy.

Level up.

• Arterial and venous thrombi (including deep vein thrombosis, pulmonary embolism).
• DIC syndrome.
• Infections, sepsis.
• Inflammation (slight increase).
• Liver disease.
• Extensive hematomas.
• Presence of rheumatoid factor.
• Pregnancy.
• Surgical interventions.
• Age over 80 years.
• Oncological diseases.
• Thrombolytic therapy.

Total mean thrombogenicity index

The total average thrombogenicity index (SITI) is a calculated indicator that allows you to assess the direction of the shift in the patient’s hemostasis system, the result of the interaction of all hemostatic systems: coagulation, anticoagulant, fibrinolytic, antifibrinolytic.When the reference limits are exceeded (SDIT> 1.1), the patient is prone to hypercoagulation, with a decrease (SDIT <0.8) - to hypocoagulation. Evaluation of the results of specific tests makes it possible to determine by what mechanisms of hemostasis the balance was disturbed and what measures must be taken to restore it.

Medical hypocoagulation: the results of emergency surgical treatment | Khasanov

Introduction

An important problem of modern medicine is aging and the associated widespread use of drugs that regulate the coagulation-anticoagulation system [1, 2].So, in the world every day more than 30 million people take non-steroidal anti-inflammatory drugs (NSAIDs) for degenerative diseases of the joints. Hemorrhagic complications associated with the adverse effects of warfarin have been described in many studies. The incidence of bleeding associated with taking the drug ranges from 7.6 to 16.5% per year, of which life-threatening bleeding occurs with a frequency of 1.3 to 2.7% [3, 4].

In recent years, in the practice of abdominal surgery departments, there has been a problem of providing surgical care to patients taking anticoagulants (warfarin) [5].Preparation of patients taking anticoagulants for planned surgical treatment is well developed and includes discontinuation of warfarin 4 days before surgery, transfer to low-molecular-weight heparin in therapeutic doses, discontinuation of low-molecular-weight heparin 12-18 hours before surgery, resumption of low-molecular-weight heparin after 6 hours after surgery, start taking warfarin whenever possible and stop using low molecular weight heparin when the international normalized ratio (INR) is 2.0 [6, 7].At the same time, there are few publications in the available literature devoted to the problems of regulation of the coagulation-anticoagulation system in the preoperative period in patients in urgent surgery and the peculiarities of the surgical treatment of patients with drug-induced hypocoagulation.

The aim of the study is to optimize emergency surgical treatment of acute cholecystitis and strangulated hernia in patients taking warfarin.

Materials and methods

The study was carried out in the period from 2013 to 2019 in the city clinical hospitals No. 8 and 13.Ufa. The study received permission from the Ethics Committee of the Bashkir State Medical University. A prerequisite was the informed consent of the patients to participate in this study. The study design included 50 patients with urgent surgical diseases of the abdominal organs. Of these, in 18 (36.0%) patients, the hypocoagulable state was caused by taking warfarin for various cardiovascular diseases. 10 (55.5%) patients had acute cholecystitis, 8 (44.5%) had strangulated inguinal hernias.The average age was 58.6 ± 12.4 years.

In the control group (32 patients) there were patients referred for emergency surgical treatment for strangulated hernias (13 – 40.6%) and acute cholecystitis (19 – 59.4%). Their average age was 54.5 ± 10.3 years. These patients did not take drugs that affect the coagulation-anticoagulation system. When examining systemic hemostasis, they did not have a hypocoagulable state. According to the type of operation performed, patients in the control group were randomized to the main groups.Research methods included traditional methods used in surgical practice in emergency patients: general blood test, general urine analysis, ultrasound, endoscopic examination, etc., as well as in hemorrhagic syndrome – activated partial thromboplastin time (APTT, s), thrombin index (PI ) according to Quick (in%), INR, fibrinogen concentration (in g / l). Statistica 12 Trial software package was used for statistical analysis.

Results and discussion

Warfarin was discontinued in patients with urgent surgical diseases after admission.It should be noted that a number of patients took warfarin for a long time haphazardly and without control of hemostasis parameters.

In patients taking warfarin, admitted on an emergency basis, phytomenadione (vitamin K) at a dose of 10 mg 2 times a day intravenously, fresh frozen plasma (FFP) at a dose of 15 to 30 ml / kg was used in the preoperative preparation.

The hemostatic effect was assessed by clinical and laboratory tests. The control of hemostasis parameters was carried out before the infusion of FFP and one hour after the end (table.one).

Table 1 . Coagulogram indices in patients taking warfarin before surgery

Table 1 . Coagulogram parameters in patients receiving warfarin during the preoperative period

In patients with strangulated hernias, preoperative preparation took no more than 2 hours. In cases of acute cholecystitis, hemostasis parameters were stabilized for 1-2 days.

Thus, the coagulogram indices in patients with acute cholecystitis did not differ significantly (p> 0.05) depending on the type of operation performed. In the group of patients taking warfarin (18 patients) admitted on an emergency basis with acute cholecystitis, cholecystectomy from the mini-access was performed in 4 (40%) patients and laparoscopic cholecystectomy (LCE) – in 6 (60%) patients.

However, despite the conducted hemostatic therapy, the condition of the tissues of patients taking warfarin had its own characteristics.Thus, diffuse bleeding of the subcutaneous tissue and other tissues was noted. During cholecystectomy, the liver capsule was thinned, the liver itself was contact bleeding, loose, and hemostasis caused serious problems.

Of the patients with strangulated hernias (8 patients), 4 underwent prosthetic hernioplasty and 4 – plastic surgery with local tissues.

Of 10 patients who took warfarin and were operated on urgently, postoperative bleeding in acute cholecystitis was in 8 (80%) people.Among patients with cholecystectomy from a mini-access, bleeding from the bladder bed was observed in 1 (10%), which required laparoscopy and coagulation of the gallbladder bed.

After LCE, 6 patients had a hematoma in the subxiphoidal approach, which required opening the hematoma. However, patients with cholecystectomy from a mini-access in all cases had a hematoma in the area of ​​the postoperative wound.

In addition, 2 patients in the postoperative period developed a hematoma in the subhepatic space with an average size of 3×4 cm, one person each in the study groups, verified by ultrasound.

In all those observed with hematomas after cholecystectomy in the subhepatic space, they did not resort to repeated operations, but were limited to inserting a catheter through the subhepatic drainage and washing the hematoma with an antiseptic solution. There were no lethal cases in this group.

Duration of drainage of the subhepatic space in the group with LCE was 5.6 ± 1.2 days, in the group with cholecystectomy from the mini-access it was 7.4 ± 1.6 days.

According to the volume of serous-hemorrhagic discharge along the drainage from the subhepatic space, there was the following distribution (table.2).

Table 2 .The amount of discharge in patients depending on the type of cholecystectomy

Table 2 . The amount of discharge in patients, depending on the type of cholecystectomy

Thus, in the group of patients with cholecystectomy from the mini-access, the volume of the sacral discharge was significantly greater and drainage was required for 8 days, while in the group with LCE, the drains were removed on the 5th day.

Coagulogram indices were studied in the postoperative period in patients with cholecystectomy and hernia repair after FFP infusion (table.3).

Table 3 . Indicators of the blood coagulation system in patients in the postoperative period

Table 3 . Indicators of the blood coagulation system in patients in the postoperative period

Thus, the coagulogram indices in the compared groups did not differ significantly (p> 0.05), however, according to the authors [7], the INR indicator does not reveal a factor IX deficiency, which affects the high likelihood of developing hemorrhagic syndrome.Clinically, this was manifested in the fact that in the group of patients with cholecystectomy from the mini-access, FFP was transfused daily for 4 days at a dose of 15 mg / kg, while in patients with LCE, a decrease in drainage through the drainage and, accordingly, intravenous infusion of FFP at a dose 15 mg / kg were administered only in the first two days of the postoperative period. In both study groups, vitamin K was administered at a dose of 10 mg 2 times a day for 6 days after surgery.

At the same time, the terms of hospitalization of patients with LCE were significantly lower than after cholecystectomy from a mini-access, 10.5 ± 1.6 and 14.4 ± 1.3 days, respectively (p <0.05).

Patients with strangulated hernias that developed while taking warfarin were divided into two groups, in the first (4 patients) plastic surgery was performed with local tissues and hematomas of the postoperative wound were not opened for 5-6 days, in the second (4 patients) prosthetic hernioplasty was performed and drainage of the postoperative wound.

In both groups there were men and operations were performed for inguinal hernias. Patients of the compared groups did not significantly differ in the size of the hernia (average), in terms of hospitalization from the moment of infringement.

Coagulogram indices did not differ significantly in the group of patients with local tissue plasty and prosthetic hernioplasty in the preoperative period (p> 0.05) (Table 4).

Table 4 . Coagulogram indices in patients taking warfarin before surgery

Table 4 . Coagulogram indices in patients receiving warfarin before surgery

After surgery, both groups received intravenous infusions of FFP at a dose of 15 mg / kg once a day for 2 days. A larger volume of infusion was considered risky due to the possibility of developing volemic overload and decompensation of existing heart failure.In addition, they used vitamin K at a dose of 10 mg 2 times a day for 6 days after the operation.

It should be noted that in patients with prosthetic hernioplasty, serous-hemorrhagic discharge was observed along the drainage from the postoperative wound. The volume of discharge averaged 165.6 ± 16.7 ml, and the termination of ichor excretion was on the 6-7th day of the postoperative period. Coagulogram indices in the compared groups did not differ significantly (p> 0.05) (table.five).

Table 5. Indicators of the blood coagulation system in patients with strangulated hernias after surgery

Table 5. Coagulation system parameters in patients with restrained hernias after surgery

Opening of a hematoma of a postoperative wound in patients with plastic hernial orifice with local tissues was performed on the 5-6th day, since the opening of the hematoma in one patient in the early stages led to a long period of expiration of the ichor (5-6 days).At the same time, the terms of hospitalization were as follows: in the group of patients with local tissue plastic surgery – 12.5 ± 1.2, in patients with prosthetic hernioplasty – 15.4 ± 1.4 days.

International standards recommend treating patients with hypocoagulation while taking warfarin using a prothrombin complex concentrate [8-10]. Due to the fact that this expensive drug is not on the list of vital and essential drugs, we did not use it.In most studies, it is believed that FFP is ineffective in eliminating bleeding in patients taking warfarin, at the same time, the available methods of controlling the coagulation-anticoagulant system are not informative enough [11-15]. Our research has established that FFP can be used in urgent surgery in patients with drug-induced hypocoagulation while taking warfarin. It was found that in patients with acute cholecystitis who took warfarin, there is contact bleeding of the liver, a prolonged outflow of serous-hemorrhagic discharge through the drains.However, the flow rate of hemorrhage in the group of patients with cholecystectomy from the mini-access is significantly greater and lasts longer in comparison with the group operated on using laparoscopy. In patients with strangulated hernias in cases of drainage of a postoperative wound, a prolonged flow of serous-hemorrhagic discharge was observed, especially in the case of using prosthetic hernioplasty.

Conclusion

Thus, in the group of patients operated on urgently for acute cholecystitis who took warfarin, laparoscopic cholecystectomy is preferable due to the fact that the drainage time, the volume of serous-hemorrhagic discharge and the hospitalization period are significantly lower in comparison with patients operated on from mini- access.In patients with strangulated hernias that developed while taking warfarin, plasty with local tissues without draining the postoperative wound is preferable, and opening the hematoma of the postoperative wound is best done on the 5-6th day.

Conflict of interest information. There is no conflict of interest.

Information about sponsorship. This work was not funded.

1.Zhuravleva L.V., Oleinik M.O. NSAID gastropathy in the practice of a family doctor. Modern gastroenterology. 2018; (3): 48-53. DOI: 10.30978 / mg-2018-3-48

2. Gao F., Chen X., Zhang J. Prevalence of gastric and small-intestinal mucosal injury in elderly patients taking enteric-coated aspirin by magnetically controlled capsule endoscopy. Gastroenterol Res Pract. 2019; 2019: 1582590. DOI: 10.1155 / 2019/1582590

3.Novikova N.A., Volovchenko A.N., Oldakovsky V.I. Gastroenterological complications of anticoagulant therapy in patients with nonvalvular atrial fibrillation. Experimental and Clinical Gastroenterology. 2015; 6 (118): 57-63.

4. Welts N.Yu., Zhuravleva EO, Bukatina TM, Kutekhova GV. Non-steroidal anti-inflammatory drugs: safety concerns. Safety and risk of pharmacotherapy. 2018; 6 (1): 11-8.DOI: 10.30895 / 2312-7821-2018-6-1-11-18

5. Moroz E.V., Karateev A.E., Kryukov E.V., Chernetsov V.A. Gastrointestinal bleeding with the use of new oral anticoagulants: epidemiology, risk factors, treatment and prevention. Scientific and practical rheumatology. 2017; 55 (6): 675-84. DOI: 10.14412 / 1995-4484-2017-675-684

6.Lee S., Choi D., Jeong W. K., Song K.D., Min J. H., Kim A.Y., et al. Frequency of hemorrhagic complications on abdominal CT in patients with warfarin therapy. Clin Imaging. 2016; 40 (3): 435-9. DOI: 10.1016 / j.clinimag.2015.12.005

7. Krylov A.Yu., Shulutko A.M., Petrovskaya A.A., Prasolov N.V., Khmyrova S.E. Experience in the treatment of bleeding and recurrence of venous thromboembolic complications that developed during therapy with vitamin K antagonists.Phlebology. 2018; 12 (1): 50-6. Doi: 10.17116 / flebo201812150-56

8. Guimaraes P.O., Pokorney S.D., Lopes R.D., Wojdyla D.M., Gersh B.J., Giczewska A., et al. Efficacy and safety of apixaban vs warfarin in patients with atrial fibrillation and prior bioprosthetic valve replacement or valve repair. Clin Cardiol. 2019; 42 (5): 568-71. Doi: 10.1002 / clc. 23178

9.Ordookhanian C., Kaloostian S.W., Kaloostian P.E. Anti-coagulation drug warfarin contributes to severe adverse outcomes in prolonged unsupervised use: a double-edged sword. Cureus. 2018; 10 (9): e3347. DOI: 10.7759 / cureus. 3347

10. Maciukaitiene J., Bilskiene D., Tamasauskas A., Bunevicius A. Prothrombin complex concentrate for warfarin-associated intracranial bleeding in neurosurgical patients: a single-center experience.Me-dicina (Kaunas). 2018; 54 (2): E22. DOI: 10.3390 / medicina54020022

11. Bogdanovski D.A., Hakakian D., DiFazio L.T., Antonioli L., Nemeth Z.H. What’s new in emergencies, trauma, and shock? using abdominal computed tomography in geriatric patients on warfarin. J Emerg Trauma Shock. 2018; 11 (2): 71-2. DOI: 10.4103 / JETS.JETS_85_17

12.Gage B.F., Bass A.R., Lin H., Woller S.C., Stevens S.M., Al-Hamma-di N., et al. Effect of genotype-guided warfarin dosing on clinical events and anticoagulation control among patients undergoing hip or knee arthroplasty: the GIFT randomized clinical trial. JAMA. 2017; 318 (12): 1115-24. DOI: 10.1001 / jama.2017.11469

13. Cohn M. R., Levack A. E., Trivedi N. N., Villa J. C., Wellman D. S., Lyden J. P., et al. The hip fracture patient on warfarin: evaluating blood loss and time to surgery.J. Orthop Trauma. 2017; 31 (8): 407-13. DOI: 10.1097 / BOT.0000000000000857

14. Bucko A.M., Makris M. Pre-operative PCC for non-bleeding patients on warfarin. Thromb Res. 2016; 139: 158-9. DOI: 10.1016 / j.throm-res.2015.12.017

15. Kelddal S., Nykjær K.M., Gregersen J.W, Birn H. Prophylactic anticoagulation in nephrotic syndrome prevents thromboembolic complications.BMC Nephrol. 2019; 20 (1): 139. DOI: 10.1186 / s12882-019-1336-8

Intracranial hemorrhages during therapy with oral anticoagulants

Intracranial hemorrhages (ICH) are the most dangerous of all hemorrhagic complications of oral anticoagulant therapy [OAC] (the development of ICH in patients on OAC therapy is associated with a poor prognosis and – this is due to an increase in the duration of bleeding and a large volume of hematoma in comparison with spontaneous hemorrhage: spontaneous hematoma, on average, continues to increase in size within 6 hours, coagulopathic – within 24 hours).The most studied (and most often used in real clinical practice) drugs of the KLA group are vitamin K antagonists (AVK), which primarily include warfarin. In 12-14% of cases, IAC occurs as a complication of VKA therapy. Since the beginning of the first decade of the XXI century. the so-called new oral anticoagulants (NOACs) – the direct thrombin inhibitor dabigatran and the inhibitors of blood coagulation factor Xa rivaroxaban and apixaban – have been introduced into clinical practice.