Drug Information: Heparin
Heparin is an injectable anticoagulant medication widely used in both prophylactic and therapeutic settings. It prevents the formation of blood clots and the growth of existing clots, thereby reducing the risk of serious complications such as deep vein thrombosis (DVT), pulmonary embolism (PE), and stroke. Heparin is available in various forms, including unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH), each with distinct pharmacokinetic properties and clinical applications.
Category
Anticoagulant
Mechanism of Action
Heparin’s primary mechanism of action involves enhancing the activity of antithrombin III (ATIII), a naturally occurring anticoagulant protein in the plasma. ATIII inhibits several coagulation factors, primarily thrombin (factor IIa) and factor Xa. Heparin binds to ATIII, causing a conformational change that dramatically accelerates ATIII’s ability to inactivate these clotting factors. Specifically, the heparin-ATIII complex neutralizes thrombin approximately 1000 times faster than ATIII alone. While both UFH and LMWH enhance ATIII activity, LMWH has a greater affinity for factor Xa inhibition compared to thrombin inhibition. This difference arises from the shorter chain length of LMWH, which is long enough to bind and activate ATIII but may not be long enough to simultaneously bind both ATIII and thrombin. This difference in mechanism contributes to the differing clinical profiles of UFH and LMWH. Heparin does not directly lyse existing clots; it prevents further clot formation and allows the body’s natural fibrinolytic system to break down existing clots.
Clinical Uses
Heparin has a wide range of clinical uses related to the prevention and treatment of thromboembolic disorders. Its primary use is in the management of venous thromboembolism (VTE), encompassing both deep vein thrombosis (DVT) and pulmonary embolism (PE). It’s also used in the prevention of DVT and PE in high-risk patients, such as those undergoing major surgery (especially orthopedic surgery), or those with prolonged immobilization. Heparin is also used in the management of acute coronary syndromes (ACS), including unstable angina and myocardial infarction (heart attack). It prevents clot formation in the coronary arteries, thereby improving blood flow to the heart. In addition, heparin is used during procedures like hemodialysis and cardiopulmonary bypass surgery to prevent clotting in the extracorporeal circuits. It can also be used to maintain the patency of intravenous catheters and arterial lines. The specific type of heparin (UFH or LMWH) and the dosage regimen used will depend on the specific clinical indication and the patient’s individual characteristics.
Dosage
Adult Dosage:
* Prophylaxis of Venous Thromboembolism (VTE): 5,000 units subcutaneously every 8-12 hours.
* Treatment of VTE: Initial bolus of 80 units/kg IV, followed by a continuous infusion of 18 units/kg/hour. Adjust infusion rate based on aPTT.
* Acute Coronary Syndromes (ACS): Initial bolus of 60-70 units/kg IV (maximum 5,000 units), followed by an infusion of 12-15 units/kg/hour (maximum 1,000 units/hour).
Pediatric Dosage: (Consult specialized pediatric dosing references for precise calculations)
* Prophylaxis of VTE: 10-20 units/kg IV every 4-6 hours or 75 units/kg SQ every 12 hours
* Treatment of VTE: Initial bolus of 75-100 units/kg IV followed by a continuous infusion of 28 units/kg/hour. Adjust infusion rate based on aPTT.
*Route of administration: Heparin is administered intravenously (IV) or subcutaneously (SQ). Intramuscular administration is contraindicated due to the risk of hematoma formation.
Indications
* Prevention and treatment of deep vein thrombosis (DVT).
* Prevention and treatment of pulmonary embolism (PE).
* Treatment of acute coronary syndromes (unstable angina, myocardial infarction).
* Anticoagulation during hemodialysis and cardiopulmonary bypass surgery.
* Prevention of clotting in arterial and venous catheters.
* Treatment of arterial thromboembolism.
Contraindications
* Active major bleeding.
* Severe thrombocytopenia (low platelet count).
* Known hypersensitivity to heparin or pork products (in some formulations).
* Recent or planned major surgery (risk of bleeding).
* Severe liver disease with coagulopathy.
* Uncontrolled hypertension.
* Intracranial hemorrhage.
FAQ
Q: What is the difference between UFH and LMWH?
A: UFH (unfractionated heparin) has a longer chain length and inhibits both thrombin and factor Xa. LMWH (low-molecular-weight heparin) has a shorter chain length and primarily inhibits factor Xa. LMWH typically has a more predictable response and requires less frequent monitoring.
Q: What are the common side effects of heparin?
A: The most common side effect is bleeding. Other side effects include thrombocytopenia (heparin-induced thrombocytopenia or HIT), injection site reactions, and hypersensitivity reactions.
Q: How is heparin monitored?
A: UFH is typically monitored using the activated partial thromboplastin time (aPTT). LMWH usually does not require routine monitoring but may be monitored with anti-Xa levels in certain patient populations (e.g., renal insufficiency, obesity).
Q: What is heparin-induced thrombocytopenia (HIT)?
A: HIT is a serious immune-mediated reaction to heparin that causes a decrease in platelet count and an increased risk of thrombosis. It requires immediate discontinuation of heparin and initiation of alternative anticoagulation.
Q: What is the antidote for heparin?
A: Protamine sulfate is the antidote for heparin. It neutralizes the anticoagulant effect of heparin.
Q: Can pregnant women use heparin?
A: Heparin, especially LMWH, is generally considered safe for use during pregnancy as it does not cross the placenta. Warfarin is typically avoided during pregnancy due to its teratogenic effects.
Q: How is heparin administered?
A: Heparin is administered intravenously (IV) or subcutaneously (SQ). It is never administered intramuscularly (IM) due to the risk of hematoma formation.
Q: What should I do if I miss a dose of heparin?
A: Contact your healthcare provider immediately for instructions. Do not double the next dose to catch up. The course of action will depend on whether you are on prophylactic or therapeutic heparin.
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