What is heparin for. Heparin: A Comprehensive Guide to Uses, Mechanisms, and Administration
What are the primary uses of heparin. How does heparin work in the body. What are the main routes of heparin administration. What are the potential side effects and contraindications of heparin. How is heparin monitored for toxicity.
Understanding Heparin: An Essential Anticoagulant
Heparin is a widely used anticoagulant medication that plays a crucial role in preventing and treating various thrombotic events. This powerful drug has become an indispensable tool in modern medicine, particularly in hospital settings. To fully appreciate its significance, it’s essential to delve into its uses, mechanisms, and administration methods.
Primary Indications for Heparin Use
Heparin’s versatility makes it a valuable asset in treating and preventing numerous medical conditions. Its primary indications include:
- Prevention and treatment of deep vein thrombosis (DVT)
- Management of pulmonary embolism (PE)
- Treatment of atrial fibrillation (AF)
- Anticoagulation during cardiac surgery
- Maintenance of extracorporeal circulation
- Prevention of clotting during dialysis and continuous renal replacement therapy (CRRT)
Is heparin used for other conditions beyond its primary indications. Indeed, heparin finds application in various off-label scenarios, such as:
- Acute coronary syndromes (ACS)
- Percutaneous coronary intervention (PCI)
- Bridging to oral anticoagulation for patients with mechanical and bioprosthetic heart valves
- Atrial fibrillation patients undergoing cardioversion
- Endocarditis
- Systemic emboli
- Venous thrombosis
The Mechanism of Action: How Heparin Works
Understanding how heparin functions in the body is crucial for healthcare professionals. The drug’s primary mechanism of action involves:
- Binding to antithrombin, causing a surface change
- Inactivating thrombin (Factor IIa) and Factor Xa
- Blocking the conversion of fibrinogen to fibrin
- Preventing clot formation
- Prolonging blood clotting time
Does heparin affect bleeding time. Interestingly, while heparin prolongs the time it takes for blood to clot, it does not affect bleeding time. This characteristic is essential for its clinical applications and safety profile.
Administration Routes and Methods
The effectiveness of heparin treatment largely depends on its proper administration. Healthcare providers must be familiar with the various routes and methods of heparin delivery:
Intravenous (IV) Administration
IV administration is the most common route for therapeutic anticoagulation. It can be administered in two ways:
- Continuous infusion: Preferred for maintaining consistent anticoagulation levels
- Intermittent administration: Used in specific scenarios, such as during cardiac catheterization procedures
Subcutaneous (SQ) Administration
SQ heparin is typically used for thromboembolism prevention. It has a slower onset of action compared to IV administration, usually taking 1 to 2 hours to become effective.
Heparin Lock Flushes
These are small-volume heparin solutions used to maintain the patency of IV lines. While effective, they require careful administration, especially in pediatric patients, to avoid inadvertent therapeutic anticoagulation.
Dosing Considerations and Adjustments
Proper dosing of heparin is critical for achieving therapeutic efficacy while minimizing the risk of adverse effects. Healthcare providers must consider several factors when determining the appropriate heparin dose:
Standard Dosing Protocol
A typical heparin drip initiation involves:
- An initial bolus injection of 80 units/kilogram intravenously
- Followed by a continuous infusion rate of 18 units/kilogram/hour
Are there special dosing considerations for certain patient populations. Yes, in obese patients, dosages are often capped at maximum bolus infusion and infusion rates to prevent overdosing.
Indication-Specific Dosing
Dosing may vary significantly based on the specific indication:
- Lower doses are typically used for acute coronary syndrome or stroke patients due to increased bleeding risk
- Dosing for catheter flushes is much lower and should not be used to achieve therapeutic anticoagulation
Renal Function Considerations
When heparin is administered and dosed by indication, no dosage adjustments are typically required for patients with renal dysfunction. This characteristic makes heparin a versatile option for patients with varying levels of kidney function.
Monitoring Heparin Therapy and Toxicity
Effective heparin therapy requires careful monitoring to ensure therapeutic efficacy and prevent complications. Healthcare providers typically use the following methods to monitor heparin therapy:
Activated Partial Thromboplastin Time (aPTT)
The aPTT is the most commonly used test to monitor heparin therapy. It measures the time it takes for blood to clot and is sensitive to the anticoagulant effects of heparin.
Anti-Factor Xa Assay
This test directly measures the inhibition of Factor Xa by heparin and may be more accurate in certain clinical situations.
Clinical Monitoring
Healthcare providers should regularly assess patients for signs of bleeding or thrombosis, which could indicate under- or over-anticoagulation.
How frequently should heparin therapy be monitored. The frequency of monitoring depends on the clinical situation, but typically, aPTT is checked every 6 hours initially, then daily once a stable dose is achieved.
Potential Adverse Effects and Contraindications
While heparin is a crucial medication in many clinical scenarios, it’s not without risks. Healthcare providers must be aware of potential adverse effects and contraindications:
Common Adverse Effects
- Bleeding: The most significant risk associated with heparin therapy
- Heparin-induced thrombocytopenia (HIT): A potentially serious immune-mediated reaction
- Osteoporosis: With long-term use
- Skin necrosis: Rare but serious complication
Contraindications
Heparin should be used with caution or avoided in patients with:
- Active bleeding or high risk of bleeding
- Severe thrombocytopenia
- History of HIT
- Hypersensitivity to heparin
Can heparin be used during pregnancy. While heparin does not cross the placenta and is generally considered safe during pregnancy, it should be used with caution and under close medical supervision.
Reversal of Heparin Anticoagulation
In cases of heparin overdose or when rapid reversal of anticoagulation is necessary, healthcare providers have options:
Protamine Sulfate
This is the primary antidote for heparin. It binds to heparin, forming an inactive complex that is then removed from circulation.
Discontinuation
In less urgent situations, simply stopping the heparin infusion may be sufficient, as heparin has a relatively short half-life.
How quickly does protamine sulfate reverse heparin’s effects. Protamine sulfate acts rapidly, with significant reversal occurring within minutes of administration.
The Role of Heparin in Modern Medicine
Heparin’s versatility and efficacy have cemented its place as a cornerstone of anticoagulation therapy in modern medicine. Its ability to prevent and treat a wide range of thrombotic conditions makes it an invaluable tool in various clinical settings, from emergency departments to operating rooms.
Emerging Research and Future Directions
Ongoing research continues to explore new applications and refinements for heparin therapy:
- Development of novel heparin formulations with improved safety profiles
- Investigation of heparin’s potential anti-inflammatory and anti-cancer properties
- Exploration of heparin’s role in treating COVID-19-associated coagulopathy
As our understanding of coagulation and thrombosis continues to evolve, so too will the applications and administration of this crucial medication.
Interprofessional Team Approach to Heparin Therapy
Effective heparin therapy requires a coordinated effort from various healthcare professionals:
- Physicians: Responsible for prescribing and overseeing heparin therapy
- Nurses: Administer heparin and monitor patients for adverse effects
- Pharmacists: Ensure proper dosing and provide guidance on drug interactions
- Laboratory technicians: Perform and interpret coagulation tests
How can healthcare teams improve patient outcomes when using heparin. By fostering open communication, adhering to evidence-based protocols, and maintaining vigilance for potential complications, interprofessional teams can optimize heparin therapy and enhance patient safety.
In conclusion, heparin remains a critical tool in the management of thrombotic disorders and anticoagulation. Its complex pharmacology, diverse applications, and potential risks underscore the need for healthcare providers to maintain a comprehensive understanding of this medication. By staying informed about the latest research and best practices in heparin therapy, healthcare professionals can continue to harness the full potential of this powerful anticoagulant to improve patient outcomes and advance medical care.
Heparin – StatPearls – NCBI Bookshelf
Continuing Education Activity
Unfractionated heparin is an anticoagulant indicated for both the prevention and treatment of thrombotic events such as deep vein thrombosis (DVT) and pulmonary embolism (PE) as well as atrial fibrillation (AF). Heparin is also used to prevent excess coagulation during procedures such as cardiac surgery, extracorporeal circulation, or dialysis, including continuous renal replacement therapy. Heparin is also widely used in the hospital for many different off-label indications. This activity outlines the indications, mechanism of action, dosing, important adverse effects, contraindications, monitoring, and toxicity of heparin and increases practitioners’ knowledge regarding how to approach this medication and use and monitor it effectively to drive better patient outcomes.
Objectives:
Review the indications, both approved and off-label, of heparin.
Identify the potential adverse effects and contraindications of heparin.
Review the monitoring for toxicity, as well as any potential reversal measures that may be available.
Explain the importance of improving care coordination among the interprofessional team to enhance the delivery of care for patients when using heparin as anticoagulation therapy.
Access free multiple choice questions on this topic.
Indications
Unfractionated heparin is an anticoagulant indicated for both the prevention and treatment of thrombotic events such as deep vein thrombosis (DVT) and pulmonary embolism (PE) as well as atrial fibrillation (AF). Heparin can also be used to prevent excess coagulation during procedures such as cardiac surgery, extracorporeal circulation, or dialysis, including continuous renal replacement therapy (CRRT).[1][2]
Heparin is widely used in the hospital for many different off-label indications, for example, patients who present with acute coronary syndromes (ACS) and who undergo percutaneous coronary intervention (PCI).
During hospitalization, heparin will be used to bridge to oral anticoagulation, warfarin for mechanical and bioprosthetic valves. The American College of Chest Physicians (ACCP) recommends using heparin for many other thrombotic states: atrial fibrillation undergoing cardioversion, endocarditis, systemic emboli, or venous thrombosis.[3][4]
Dosing recommendations vary for each indication. Most heparin drips will be initiated with a bolus injection of 80 units/kilogram intravenously, followed by a continuous infusion rate of 18 units/kilogram/hour. In obese populations, these dosages are capped off at a maximum bolus infusion and maximum infusion rate. Dosing in some situations is much lower with different maximum doses. For example, in patients with acute coronary syndrome or stroke, the dose is much lower due to an increased risk for bleeding. When heparin is administered and dosed by indication, there are no dosage adjustments required for renal dysfunction.[1][3]
Heparin is also useful in smaller volumes as lock flushes.
Due to the increase in adverse effects and exposure to heparin, these are not used as often in clinical practice. These are intended to maintain patency for IV lines and should not be used to achieve therapeutic anticoagulation. Lock flushes are usually dispensed as a 1 to 5 mL volume syringe used for catheter flush only. A small volume of heparin is instilled into the catheter tip and flushed daily. Extra caution should be observed in the administration of heparin lock solution frequently in a 24 hour period with pediatric patients. Dependent upon the concentration, if instilling a lock flush, this could be close to a therapeutic dose of heparin in some pediatric patients.[1][2][3]
Mechanism of Action
Once administered, heparin binds to several proteins; however, it is binding to an antithrombin that is important, as this causes a surface change and inactivates thrombin. Binding to antithrombin blocks several different factors of the clotting cascade, but two are predominant: thrombin (Factor IIa) and Factor Xa.
By inactivating thrombin, it blocks the conversion of fibrinogen to fibrin; this prevents the formation of clots and prolongs the clotting time of blood. Heparin does not affect bleeding time, but it does prolong the time that blood takes to clot.[1][2]
Administration
Heparin administration can be by intravenous (IV) route or subcutaneous SQ) route. Intravenous heparin is continuously administered for therapeutic anticoagulation, while intermittent subcutaneous administration is used to prevent thromboembolism. Intermittent IV administration is also an option. For example, heparin is given intermittently by the interventional cardiologist in the cardiac catheterization lab, dependent upon laboratory markers throughout the case. When administered SQ, the onset of action is usually within 1 to 2 hours compared to an immediate anticoagulant effect with IV administration of heparin. There was an assessment of intramuscular (IM) injection, but researchers observed an increased level of pain, irritation, and hematoma formation with IM injections of heparin.
[1][3]
Adverse Effects
Heparin use’s typical adverse effects include bleeding, thrombocytopenia, injection site reactions, and other adverse effects only seen with chronic heparin administration. Bleeding is a major complication associated with heparin use. Patients should undergo monitoring for new bleeding that may present in the urine or stool. Bleeding may also present as bruising, petechial rash, and nosebleeds.[2]
Thrombocytopenia typically occurs in up to 30% of patients who receive heparin. Most often, this is not significant; however, there is a form of thrombocytopenia that is more serious, known as heparin-induced thrombocytopenia (HIT). Thrombocytopenia can be classified as Type I or Type II. Type I is a non-immunogenic interaction with platelets that typically occurs within the first 48 to 72 hours of initiation of heparin. The drop in platelet count is usually temporary and will recover upon cessation of heparin. Type II thrombocytopenia is more commonly known as heparin-induced thrombocytopenia; this is immune-related thrombocytopenia that occurs when heparin binds to the protein platelet factor 4 (PF4).
This complex alerts the immune system and causes an immune-mediated reaction with platelets. Platelets are activated and consumed by clot formation providing a pro-thrombotic environment with a low platelet count. Heparin-induced thrombocytopenia usually occurs about five days into heparin therapy. Thrombosis can form and cause severe HITT (heparin-induced thrombocytopenia and thrombosis). Serious events seen with thrombosis include pulmonary embolism, deep vein thrombosis, stroke, myocardial infarction, and thrombosis in main arteries to organs that could lead to severe complications, including limb amputation or death.[5]
Other adverse effects that occur with the use of heparin include injection site reactions, hyperkalemia, alopecia, and osteoporosis. Osteopenia and osteoporosis have correlations with chronic heparin use, but not with acute use of heparin.[5]
Contraindications
A patient should not receive heparin if[5]:
The platelet count is 100,000/mm or lower.
The patient cannot have routine monitoring tests performed to monitor therapeutic heparin.
The patient has an active, uncontrollable bleed except for disseminated intravascular coagulation (DIC).
Patients with a history of heparin-induced thrombocytopenia should also avoid heparin use.
Monitoring
Therapeutic monitoring for heparin includes activated partial thromboplastin time (aPTT) and activated clotting time (ACT). Both of these are aspects of clotting time, which are prolonged by therapeutic heparin doses. Activated partial thromboplastin time is performed at baseline and every 6 hours until 2 or more therapeutic values are obtained, then aPTT can be assessed every 24 hours. Dose titrations are made based on the results of the aPTT. Hospitals have dosing nomograms specific to their target aPTT, which may vary depending upon the laboratory reagent used for their test. Therapeutic aPTT is considered therapeutic at 1.
5 to 2 times control, which also varies from facility to facility based on controls.[1]
ACT is less sensitive than aPTT. ACT will only detect abnormalities when there is a 95% abnormality rate in the factors, whereas aPTT can detect when there is a 70% abnormality. ACT may also be affected when platelets are abnormal, which can result from the administration of heparin. ACT is a point of care test, which makes testing at the bedside more convenient with a quick turnaround. For these reasons, ACT is generally limited to use in cardiopulmonary bypass, ECMO (extracorporeal membrane oxygenation), or PCI (percutaneous coronary intervention). ACT monitoring during bypass is to ensure that the blood is thin enough to prevent clotting of the heart and lung machine. Most practitioners will aim for a goal ACT greater than 400 during CPB (cardiopulmonary bypass).[6][7]
Another form of monitoring includes anti-factor Xa activity levels. A level is considered therapeutic at 0.3 to 0.7 international units/milliliter.
This monitoring is often reserved for use in patients where aPTT monitoring is unreliable, but some institutions have protocol-driven titrations based on anti-factor Xa levels.[8]
Monitoring for adverse effects includes hemoglobin, hematocrit, platelet count (every 2 to 3 days while on therapy), and vital signs. If hemoglobin, hematocrit, or blood pressures drop, the possibility of hemorrhage should be investigated. If the platelet count falls below 100000/mm3, then the risk and benefit of continuing heparin should be evaluated, and an alternative anticoagulant is the recommended course. A HIT 4-T score should be calculated when HIT is suspected.[1]
Toxicity
When heparin toxicity occurs, protamine is recommended for reversal of heparin’s anticoagulant effect. Patients with life-threatening or severe bleeding or patients who undergo surgery may require protamine for reversal. Neutralization of heparin occurs when protamine binds to the heparin by ionic properties. The protamine-heparin complex is inactive, and heparin is unable to act as an anticoagulant.
Protamine administration should be via slow IV push with no more than 50 mg over 10 minutes. Administration of protamine too rapidly has been associated with severe reactions, most commonly, hypotension, pulmonary edema, pulmonary vasoconstriction, and pulmonary hypertension. These effects also present with high doses of protamine, repeat doses of protamine, and previous exposure or current exposure. Anaphylaxis can also occur with protamine administration. Because of heparin’s short half-life, time from administration of heparin is used to determine the initial dose of protamine needed for reversal. Every 1mg of protamine administered neutralizes 100 units of heparin. Heparin neutralization should occur within about 5 minutes of protamine administration.[1]
Enhancing Healthcare Team Outcomes
Heparin enjoys wide use in the hospital setting for several different indications that require specific dosing and administration routes. The use of heparin is a balance between effective anticoagulation to treat or prevent thromboembolism and safety.
According to ISMP (Institute for Safe Medication Practices), heparin is in the high-risk medication classification that correlates with a multitude of patient safety errors and has the potential to cause significant harm. Many factors can contribute to potential errors, including dosing, monitoring, adverse effects, and dispensing logistics. To mitigate these potential errors, major safety monitoring organizations and several clinical studies have been conducted to delineate the most effective management standards for hospitals. Collectively, more information available about past errors can influence practice to protect patients in the future.[9]
There are numerous documented heparin errors attributed to manufacturer labeling and the many stock vials and bags available. After fatal errors in the pediatric population, a labeling update was instituted in 2013 to display the total number of units in each heparin vial. Limiting current stock to a standard heparin bag solution and standard vial concentrations for automatic dispensing cabinets may also help to prevent errors.
Dosing of heparin varies from indication, and dosage is by weight. Weight-based dosing offers another area for potential errors with calculations. Whether the initial dose is ordered as a unit/kilogram/hour rate versus a unit/hour versus milliliters/hour can significantly affect the initial dose. Current recommendations are that hospitals have a standard initiation protocol driven by dosing data for each indication.
Monitoring aPTT levels throughout heparin therapy can also offer an area for errors. Protocols are in place to instruct nursing staff on titration instructions based solely on the aPTT level. However, at that time, a new rate must be calculated and titrated based on the instructions on the protocol. These protocols have correlated with an increase in the amount of time that the aPTT is within the therapeutic range, which would improve the outcomes of patients with thromboembolism.[10][11]
The heparin prescribing information states that dosing and titration often require an interprofessional double check to ensure the correct dose and indication.
One study evaluated the use of pharmacist management of heparin that showed significantly fewer errors in the hospitals where pharmacists were managing anticoagulation.[12]
In conclusion, heparin is a high-risk medication that requires many safety barriers to avoid errors and protect patients; this takes an interprofessional team approach in the hospitals consisting of clinicians (MDs, DOs, NPs, PAs), nurses, and pharmacists. [Level 5] It also requires an even greater approach from safety organizations and manufacturing companies.
Review Questions
Access free multiple choice questions on this topic.
Comment on this article.
References
- 1.
Holbrook A, Schulman S, Witt DM, Vandvik PO, Fish J, Kovacs MJ, Svensson PJ, Veenstra DL, Crowther M, Guyatt GH. Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.
Chest. 2012 Feb;141(2 Suppl):e152S-e184S. [PMC free article: PMC3278055] [PubMed: 22315259]- 2.
Mulloy B, Hogwood J, Gray E, Lever R, Page CP. Pharmacology of Heparin and Related Drugs. Pharmacol Rev. 2016 Jan;68(1):76-141. [PubMed: 26672027]
- 3.
Hirsh J, Anand SS, Halperin JL, Fuster V., American Heart Association. AHA Scientific Statement: Guide to anticoagulant therapy: heparin: a statement for healthcare professionals from the American Heart Association. Arterioscler Thromb Vasc Biol. 2001 Jul;21(7):E9-9. [PubMed: 11451763]
- 4.
Hemker HC. A century of heparin: past, present and future. J Thromb Haemost. 2016 Dec;14(12):2329-2338. [PubMed: 27862941]
- 5.
Ahmed I, Majeed A, Powell R. Heparin induced thrombocytopenia: diagnosis and management update. Postgrad Med J. 2007 Sep;83(983):575-82. [PMC free article: PMC2600013] [PubMed: 17823223]
- 6.
De Waele JJ, Van Cauwenberghe S, Hoste E, Benoit D, Colardyn F.
The use of the activated clotting time for monitoring heparin therapy in critically ill patients. Intensive Care Med. 2003 Feb;29(2):325-8. [PubMed: 12594595]- 7.
Atallah S, Liebl M, Fitousis K, Bostan F, Masud F. Evaluation of the activated clotting time and activated partial thromboplastin time for the monitoring of heparin in adult extracorporeal membrane oxygenation patients. Perfusion. 2014 Sep;29(5):456-61. [PubMed: 24570077]
- 8.
Vandiver JW, Vondracek TG. Antifactor Xa levels versus activated partial thromboplastin time for monitoring unfractionated heparin. Pharmacotherapy. 2012 Jun;32(6):546-58. [PubMed: 22531940]
- 9.
Barclay CA, Vonderhaar KJ, Clark EA. The development of evidence-based care recommendations to improve the safe use of anticoagulants in children. J Pediatr Pharmacol Ther. 2012 Apr;17(2):155-8. [PMC free article: PMC3470435] [PubMed: 23118667]
- 10.
Raschke RA, Reilly BM, Guidry JR, Fontana JR, Srinivas S.
The weight-based heparin dosing nomogram compared with a “standard care” nomogram. A randomized controlled trial. Ann Intern Med. 1993 Nov 01;119(9):874-81. [PubMed: 8214998]- 11.
Raschke RA, Gollihare B, Peirce JC. The effectiveness of implementing the weight-based heparin nomogram as a practice guideline. Arch Intern Med. 1996 Aug 12-26;156(15):1645-9. [PubMed: 8694662]
- 12.
Bond CA, Raehl CL. Pharmacist-provided anticoagulation management in United States hospitals: death rates, length of stay, Medicare charges, bleeding complications, and transfusions. Pharmacotherapy. 2004 Aug;24(8):953-63. [PubMed: 15338843]
Chest. 2012 Feb;141(2 Suppl):e152S-e184S. [PMC free article: PMC3278055] [PubMed: 22315259]
The use of the activated clotting time for monitoring heparin therapy in critically ill patients. Intensive Care Med. 2003 Feb;29(2):325-8. [PubMed: 12594595]
The weight-based heparin dosing nomogram compared with a “standard care” nomogram. A randomized controlled trial. Ann Intern Med. 1993 Nov 01;119(9):874-81. [PubMed: 8214998]Disclosure: Laken Warnock declares no relevant financial relationships with ineligible companies.
Disclosure: Davis Huang declares no relevant financial relationships with ineligible companies.
Heparin – StatPearls – NCBI Bookshelf
Continuing Education Activity
Unfractionated heparin is an anticoagulant indicated for both the prevention and treatment of thrombotic events such as deep vein thrombosis (DVT) and pulmonary embolism (PE) as well as atrial fibrillation (AF).
Heparin is also used to prevent excess coagulation during procedures such as cardiac surgery, extracorporeal circulation, or dialysis, including continuous renal replacement therapy. Heparin is also widely used in the hospital for many different off-label indications. This activity outlines the indications, mechanism of action, dosing, important adverse effects, contraindications, monitoring, and toxicity of heparin and increases practitioners’ knowledge regarding how to approach this medication and use and monitor it effectively to drive better patient outcomes.
Objectives:
Review the indications, both approved and off-label, of heparin.
Identify the potential adverse effects and contraindications of heparin.
Review the monitoring for toxicity, as well as any potential reversal measures that may be available.
Explain the importance of improving care coordination among the interprofessional team to enhance the delivery of care for patients when using heparin as anticoagulation therapy.
Access free multiple choice questions on this topic.
Indications
Unfractionated heparin is an anticoagulant indicated for both the prevention and treatment of thrombotic events such as deep vein thrombosis (DVT) and pulmonary embolism (PE) as well as atrial fibrillation (AF). Heparin can also be used to prevent excess coagulation during procedures such as cardiac surgery, extracorporeal circulation, or dialysis, including continuous renal replacement therapy (CRRT).[1][2]
Heparin is widely used in the hospital for many different off-label indications, for example, patients who present with acute coronary syndromes (ACS) and who undergo percutaneous coronary intervention (PCI). During hospitalization, heparin will be used to bridge to oral anticoagulation, warfarin for mechanical and bioprosthetic valves. The American College of Chest Physicians (ACCP) recommends using heparin for many other thrombotic states: atrial fibrillation undergoing cardioversion, endocarditis, systemic emboli, or venous thrombosis.
[3][4]
Dosing recommendations vary for each indication. Most heparin drips will be initiated with a bolus injection of 80 units/kilogram intravenously, followed by a continuous infusion rate of 18 units/kilogram/hour. In obese populations, these dosages are capped off at a maximum bolus infusion and maximum infusion rate. Dosing in some situations is much lower with different maximum doses. For example, in patients with acute coronary syndrome or stroke, the dose is much lower due to an increased risk for bleeding. When heparin is administered and dosed by indication, there are no dosage adjustments required for renal dysfunction.[1][3]
Heparin is also useful in smaller volumes as lock flushes. Due to the increase in adverse effects and exposure to heparin, these are not used as often in clinical practice. These are intended to maintain patency for IV lines and should not be used to achieve therapeutic anticoagulation. Lock flushes are usually dispensed as a 1 to 5 mL volume syringe used for catheter flush only.
A small volume of heparin is instilled into the catheter tip and flushed daily. Extra caution should be observed in the administration of heparin lock solution frequently in a 24 hour period with pediatric patients. Dependent upon the concentration, if instilling a lock flush, this could be close to a therapeutic dose of heparin in some pediatric patients.[1][2][3]
Mechanism of Action
Once administered, heparin binds to several proteins; however, it is binding to an antithrombin that is important, as this causes a surface change and inactivates thrombin. Binding to antithrombin blocks several different factors of the clotting cascade, but two are predominant: thrombin (Factor IIa) and Factor Xa. By inactivating thrombin, it blocks the conversion of fibrinogen to fibrin; this prevents the formation of clots and prolongs the clotting time of blood. Heparin does not affect bleeding time, but it does prolong the time that blood takes to clot.[1][2]
Administration
Heparin administration can be by intravenous (IV) route or subcutaneous SQ) route.
Intravenous heparin is continuously administered for therapeutic anticoagulation, while intermittent subcutaneous administration is used to prevent thromboembolism. Intermittent IV administration is also an option. For example, heparin is given intermittently by the interventional cardiologist in the cardiac catheterization lab, dependent upon laboratory markers throughout the case. When administered SQ, the onset of action is usually within 1 to 2 hours compared to an immediate anticoagulant effect with IV administration of heparin. There was an assessment of intramuscular (IM) injection, but researchers observed an increased level of pain, irritation, and hematoma formation with IM injections of heparin.[1][3]
Adverse Effects
Heparin use’s typical adverse effects include bleeding, thrombocytopenia, injection site reactions, and other adverse effects only seen with chronic heparin administration. Bleeding is a major complication associated with heparin use. Patients should undergo monitoring for new bleeding that may present in the urine or stool.
Bleeding may also present as bruising, petechial rash, and nosebleeds.[2]
Thrombocytopenia typically occurs in up to 30% of patients who receive heparin. Most often, this is not significant; however, there is a form of thrombocytopenia that is more serious, known as heparin-induced thrombocytopenia (HIT). Thrombocytopenia can be classified as Type I or Type II. Type I is a non-immunogenic interaction with platelets that typically occurs within the first 48 to 72 hours of initiation of heparin. The drop in platelet count is usually temporary and will recover upon cessation of heparin. Type II thrombocytopenia is more commonly known as heparin-induced thrombocytopenia; this is immune-related thrombocytopenia that occurs when heparin binds to the protein platelet factor 4 (PF4). This complex alerts the immune system and causes an immune-mediated reaction with platelets. Platelets are activated and consumed by clot formation providing a pro-thrombotic environment with a low platelet count.
Heparin-induced thrombocytopenia usually occurs about five days into heparin therapy. Thrombosis can form and cause severe HITT (heparin-induced thrombocytopenia and thrombosis). Serious events seen with thrombosis include pulmonary embolism, deep vein thrombosis, stroke, myocardial infarction, and thrombosis in main arteries to organs that could lead to severe complications, including limb amputation or death.[5]
Other adverse effects that occur with the use of heparin include injection site reactions, hyperkalemia, alopecia, and osteoporosis. Osteopenia and osteoporosis have correlations with chronic heparin use, but not with acute use of heparin.[5]
Contraindications
A patient should not receive heparin if[5]:
The platelet count is 100,000/mm or lower.
The patient cannot have routine monitoring tests performed to monitor therapeutic heparin.
The patient has an active, uncontrollable bleed except for disseminated intravascular coagulation (DIC).
Patients with a history of heparin-induced thrombocytopenia should also avoid heparin use.
Monitoring
Therapeutic monitoring for heparin includes activated partial thromboplastin time (aPTT) and activated clotting time (ACT). Both of these are aspects of clotting time, which are prolonged by therapeutic heparin doses. Activated partial thromboplastin time is performed at baseline and every 6 hours until 2 or more therapeutic values are obtained, then aPTT can be assessed every 24 hours. Dose titrations are made based on the results of the aPTT. Hospitals have dosing nomograms specific to their target aPTT, which may vary depending upon the laboratory reagent used for their test. Therapeutic aPTT is considered therapeutic at 1.5 to 2 times control, which also varies from facility to facility based on controls.[1]
ACT is less sensitive than aPTT. ACT will only detect abnormalities when there is a 95% abnormality rate in the factors, whereas aPTT can detect when there is a 70% abnormality.
ACT may also be affected when platelets are abnormal, which can result from the administration of heparin. ACT is a point of care test, which makes testing at the bedside more convenient with a quick turnaround. For these reasons, ACT is generally limited to use in cardiopulmonary bypass, ECMO (extracorporeal membrane oxygenation), or PCI (percutaneous coronary intervention). ACT monitoring during bypass is to ensure that the blood is thin enough to prevent clotting of the heart and lung machine. Most practitioners will aim for a goal ACT greater than 400 during CPB (cardiopulmonary bypass).[6][7]
Another form of monitoring includes anti-factor Xa activity levels. A level is considered therapeutic at 0.3 to 0.7 international units/milliliter. This monitoring is often reserved for use in patients where aPTT monitoring is unreliable, but some institutions have protocol-driven titrations based on anti-factor Xa levels.[8]
Monitoring for adverse effects includes hemoglobin, hematocrit, platelet count (every 2 to 3 days while on therapy), and vital signs.
If hemoglobin, hematocrit, or blood pressures drop, the possibility of hemorrhage should be investigated. If the platelet count falls below 100000/mm3, then the risk and benefit of continuing heparin should be evaluated, and an alternative anticoagulant is the recommended course. A HIT 4-T score should be calculated when HIT is suspected.[1]
Toxicity
When heparin toxicity occurs, protamine is recommended for reversal of heparin’s anticoagulant effect. Patients with life-threatening or severe bleeding or patients who undergo surgery may require protamine for reversal. Neutralization of heparin occurs when protamine binds to the heparin by ionic properties. The protamine-heparin complex is inactive, and heparin is unable to act as an anticoagulant. Protamine administration should be via slow IV push with no more than 50 mg over 10 minutes. Administration of protamine too rapidly has been associated with severe reactions, most commonly, hypotension, pulmonary edema, pulmonary vasoconstriction, and pulmonary hypertension.
These effects also present with high doses of protamine, repeat doses of protamine, and previous exposure or current exposure. Anaphylaxis can also occur with protamine administration. Because of heparin’s short half-life, time from administration of heparin is used to determine the initial dose of protamine needed for reversal. Every 1mg of protamine administered neutralizes 100 units of heparin. Heparin neutralization should occur within about 5 minutes of protamine administration.[1]
Enhancing Healthcare Team Outcomes
Heparin enjoys wide use in the hospital setting for several different indications that require specific dosing and administration routes. The use of heparin is a balance between effective anticoagulation to treat or prevent thromboembolism and safety. According to ISMP (Institute for Safe Medication Practices), heparin is in the high-risk medication classification that correlates with a multitude of patient safety errors and has the potential to cause significant harm.
Many factors can contribute to potential errors, including dosing, monitoring, adverse effects, and dispensing logistics. To mitigate these potential errors, major safety monitoring organizations and several clinical studies have been conducted to delineate the most effective management standards for hospitals. Collectively, more information available about past errors can influence practice to protect patients in the future.[9]
There are numerous documented heparin errors attributed to manufacturer labeling and the many stock vials and bags available. After fatal errors in the pediatric population, a labeling update was instituted in 2013 to display the total number of units in each heparin vial. Limiting current stock to a standard heparin bag solution and standard vial concentrations for automatic dispensing cabinets may also help to prevent errors.
Dosing of heparin varies from indication, and dosage is by weight. Weight-based dosing offers another area for potential errors with calculations.
Whether the initial dose is ordered as a unit/kilogram/hour rate versus a unit/hour versus milliliters/hour can significantly affect the initial dose. Current recommendations are that hospitals have a standard initiation protocol driven by dosing data for each indication.
Monitoring aPTT levels throughout heparin therapy can also offer an area for errors. Protocols are in place to instruct nursing staff on titration instructions based solely on the aPTT level. However, at that time, a new rate must be calculated and titrated based on the instructions on the protocol. These protocols have correlated with an increase in the amount of time that the aPTT is within the therapeutic range, which would improve the outcomes of patients with thromboembolism.[10][11]
The heparin prescribing information states that dosing and titration often require an interprofessional double check to ensure the correct dose and indication. One study evaluated the use of pharmacist management of heparin that showed significantly fewer errors in the hospitals where pharmacists were managing anticoagulation.
[12]
In conclusion, heparin is a high-risk medication that requires many safety barriers to avoid errors and protect patients; this takes an interprofessional team approach in the hospitals consisting of clinicians (MDs, DOs, NPs, PAs), nurses, and pharmacists. [Level 5] It also requires an even greater approach from safety organizations and manufacturing companies.
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References
- 1.
Holbrook A, Schulman S, Witt DM, Vandvik PO, Fish J, Kovacs MJ, Svensson PJ, Veenstra DL, Crowther M, Guyatt GH. Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e152S-e184S. [PMC free article: PMC3278055] [PubMed: 22315259]
- 2.
Mulloy B, Hogwood J, Gray E, Lever R, Page CP.
Pharmacology of Heparin and Related Drugs. Pharmacol Rev. 2016 Jan;68(1):76-141. [PubMed: 26672027]- 3.
Hirsh J, Anand SS, Halperin JL, Fuster V., American Heart Association. AHA Scientific Statement: Guide to anticoagulant therapy: heparin: a statement for healthcare professionals from the American Heart Association. Arterioscler Thromb Vasc Biol. 2001 Jul;21(7):E9-9. [PubMed: 11451763]
- 4.
Hemker HC. A century of heparin: past, present and future. J Thromb Haemost. 2016 Dec;14(12):2329-2338. [PubMed: 27862941]
- 5.
Ahmed I, Majeed A, Powell R. Heparin induced thrombocytopenia: diagnosis and management update. Postgrad Med J. 2007 Sep;83(983):575-82. [PMC free article: PMC2600013] [PubMed: 17823223]
- 6.
De Waele JJ, Van Cauwenberghe S, Hoste E, Benoit D, Colardyn F. The use of the activated clotting time for monitoring heparin therapy in critically ill patients. Intensive Care Med. 2003 Feb;29(2):325-8.
[PubMed: 12594595]- 7.
Atallah S, Liebl M, Fitousis K, Bostan F, Masud F. Evaluation of the activated clotting time and activated partial thromboplastin time for the monitoring of heparin in adult extracorporeal membrane oxygenation patients. Perfusion. 2014 Sep;29(5):456-61. [PubMed: 24570077]
- 8.
Vandiver JW, Vondracek TG. Antifactor Xa levels versus activated partial thromboplastin time for monitoring unfractionated heparin. Pharmacotherapy. 2012 Jun;32(6):546-58. [PubMed: 22531940]
- 9.
Barclay CA, Vonderhaar KJ, Clark EA. The development of evidence-based care recommendations to improve the safe use of anticoagulants in children. J Pediatr Pharmacol Ther. 2012 Apr;17(2):155-8. [PMC free article: PMC3470435] [PubMed: 23118667]
- 10.
Raschke RA, Reilly BM, Guidry JR, Fontana JR, Srinivas S. The weight-based heparin dosing nomogram compared with a “standard care” nomogram. A randomized controlled trial.
Ann Intern Med. 1993 Nov 01;119(9):874-81. [PubMed: 8214998]- 11.
Raschke RA, Gollihare B, Peirce JC. The effectiveness of implementing the weight-based heparin nomogram as a practice guideline. Arch Intern Med. 1996 Aug 12-26;156(15):1645-9. [PubMed: 8694662]
- 12.
Bond CA, Raehl CL. Pharmacist-provided anticoagulation management in United States hospitals: death rates, length of stay, Medicare charges, bleeding complications, and transfusions. Pharmacotherapy. 2004 Aug;24(8):953-63. [PubMed: 15338843]
Pharmacology of Heparin and Related Drugs. Pharmacol Rev. 2016 Jan;68(1):76-141. [PubMed: 26672027]
[PubMed: 12594595]
Ann Intern Med. 1993 Nov 01;119(9):874-81. [PubMed: 8214998]Disclosure: Laken Warnock declares no relevant financial relationships with ineligible companies.
Disclosure: Davis Huang declares no relevant financial relationships with ineligible companies.
Heparin for the prevention of deep vein thrombosis or pulmonary embolism in acutely ill medical patients (excluding patients with stroke or myocardial infarction)
Patients admitted to hospital with an acute/emergency condition may develop blood clots in their veins.
These types of blood clots are called deep vein thrombosis (DVT) and can break away from the wall of a blood vessel and travel to the lungs, causing death. This is called pulmonary embolism (PE). These types of blood clots and their prevention have been extensively studied in surgical patients, but they are less well studied in non-surgical and medical patients, who make up the majority of hospital patients. Medical patients differ from surgical patients in terms of health, progression of thrombi, and the impact that preventive measures can have. Therefore, the extensive experience of research on thromboprophylaxis in surgical patients is not necessarily applicable to non-surgical patients.
Heparin is a blood thinner that has been shown to reduce the occurrence of blood clots in post-surgery patients. Heparin exists in two forms: the original unfractionated heparin (UFH) and a newer form called low molecular weight heparin (LMWH). The aim of this review is to determine the efficacy and safety of heparin (UFH or LMWH) for the prevention of DVT and PE in non-surgical, therapeutic patients admitted to the hospital, excluding those admitted to the hospital with a heart attack or stroke or who require treatment in intensive care unit.
The outcomes examined in this review were: DVT and PE that did not result in death; PE, which led to death; combined outcome – non-fatal and fatal PE; death from all causes; complications in the form of bleeding and thrombocytopenia – a condition that can be caused by heparin, and leads to a decrease in the number of platelets in the blood.
This review of 16 clinical trials involving 34,369 non-surgical acutely ill patients found that heparin reduced the number of patients with DVT but also increased the risk of bleeding complications compared with placebo or no heparin . We had some concerns about the reliability of the results from non-blinded studies, which accounted for just under half of all studies. In addition, most of the studies did not explain how the allocation to treatment groups was made. The lower risk of PE (by summing up deaths and non-causes) with heparin may have been an accidental effect. There was no clear evidence of a difference in the incidence of death or thrombocytopenia.
The review also found that patients given LMWH had fewer deep vein thromboses and fewer bleeding complications than those given UFH, suggesting that LMWH is more effective and carries a lower risk of adverse events. thromboprophylaxis events than UFH. There was no clear evidence of a difference between LMWH and UFH in terms of PE, death, or thrombocytopenia.
Translation notes:
Translation: Zamaletdinova Aliya Rafaelevna. Editing: Giniyatullina Leyla Kamilovna and Ziganshina Liliya Evgenievna. Project coordination for translation into Russian: Cochrane Russia – Cochrane Russia (branch of the Northern Cochrane Center on the basis of Kazan Federal University). For questions related to this translation, please contact us at: [email protected]; [email protected]
💊 Ingredients of Heparin ✅ Use of Heparin Save Search for analogues Interaction Description of the active ingredients of the preparation Heparin The scientific information provided is general and cannot be used to make decisions. Update date: 2019.12.04 Marketing authorization holder: SYNTHESIS JSC ATX code: B01AB01 (Heparin) Active substance: Rec. WHO registered Dosage form
Release form, packaging and composition |
(4363)
INN
after surgical operations.
| D59.3 | Hemolytic uremic syndrome |
| D65 | Disseminated intravascular coagulation [defibrination syndrome] |
| I20.0 | Unstable angina |
| I21 | Acute myocardial infarction |
| I26 | Pulmonary embolism |
| I33.9 | Acute endocarditis, unspecified |
I34. 0 | Mitral (valvular) insufficiency |
| I48 | Atrial fibrillation and flutter |
| I74 | Arterial embolism and thrombosis |
| I80 | Phlebitis and thrombophlebitis |
| I82 | Embolism and thrombosis of other veins |
| N00 | Acute nephritic syndrome (acute glomerulonephritis) |
| N03 | Chronic nephritic syndrome |
| N08.5 | Glomerular lesions in systemic connective tissue diseases |
| Z51.4 | Preparatory procedures for subsequent treatment or examination, not elsewhere classified |
Dosage regimen
The method of administration and dosing regimen of a particular drug depends on its form of release and other factors.
The optimal dosage regimen is determined by the doctor. Compliance of the dosage form of a particular drug with indications for use and dosing regimen should be strictly observed.
Individual, depending on the dosage form used, indications, clinical situation and age of the patient.
Side effects
On the part of the blood coagulation system: possible bleeding of the gastrointestinal tract and urinary tract, bleeding at the injection site, in areas subjected to pressure, from surgical wounds, as well as hemorrhages in other organs, hematuria, thrombocytopenia.
From the digestive system: nausea, loss of appetite, vomiting, diarrhea, increased activity of liver transaminases.
Allergic reactions: flushing of the skin, drug fever, urticaria, rhinitis, pruritus and sensation of heat in the soles, bronchospasm, collapse, anaphylactic shock.
On the part of the blood coagulation system: thrombocytopenia (may be severe up to death) with subsequent development of skin necrosis, arterial thrombosis, accompanied by the development of gangrene, myocardial infarction, stroke.
From the musculoskeletal system: with prolonged use – osteoporosis, spontaneous fractures, soft tissue calcification.
Local reactions: irritation, pain, hyperemia, hematoma and ulceration at the injection site.
Other: transient alopecia, hypoaldosteronism.
Contraindications for use
Bleeding, diseases accompanied by impaired blood coagulation, suspected intracranial hemorrhage, cerebral aneurysm, hemorrhagic stroke, dissecting aortic aneurysm, antiphospholipid syndrome, malignant arterial hypertension, subacute bacterial endocarditis, erosive ulcerative lesions of the gastrointestinal tract , severe lesions of the liver parenchyma, cirrhosis of the liver with varicose veins of the esophagus, malignant neoplasms in the liver, shock conditions, recent surgical interventions on the eyes, brain, prostate, liver and biliary tract, condition after spinal cord puncture, menstruation, threatened miscarriage, childbirth (including recent), hypersensitivity to heparin.
Use during pregnancy and lactation
Use during pregnancy is possible only under strict indications, under close medical supervision.
Contraindication: threatened miscarriage, childbirth (including recent).
Can be used during breastfeeding if indicated.
Use for violations of liver function
Contraindications: severe lesions of the liver parenchyma, cirrhosis of the liver with varicose veins of the esophagus, malignant neoplasms in the liver.
Use for impaired renal function
Used when indicated in patients with severe kidney disease.
Use in children
May be used in children if indicated.
Use in elderly patients
Use with caution in elderly patients (over 60 years, especially women).
Special instructions
Use with caution in patients suffering from polyvalent allergies (including bronchial asthma), arterial hypertension, dental procedures, diabetes mellitus, endocarditis, pericarditis, in the presence of an intrauterine contraceptive, with active tuberculosis, radiation therapy, liver failure, chronic renal failure, in elderly patients (over 60 years, especially women).
IM administration of heparin is not recommended due to the possibility of developing a hematoma, as well as IM administration of other drugs during treatment with heparin.
Use with caution externally for bleeding and conditions of increased bleeding, thrombocytopenia.
During treatment with heparin, monitoring of blood coagulation parameters is necessary.
Only normal saline is used to dilute heparin.
With the development of severe thrombocytopenia (a decrease in the number of platelets by 2 times from the original number or below 100,000 / µl), it is necessary to urgently stop the use of heparin.
The risk of bleeding can be minimized with careful evaluation of contraindications, regular laboratory monitoring of blood clotting, and adequate dosing.
Drug interactions
The anticoagulant effect of heparin is enhanced by the simultaneous use of anticoagulants, antiplatelet agents and NSAIDs.
Ergot alkaloids, thyroxine, tetracycline, antihistamines, and nicotine reduce the effect of heparin.