Heparin

Usage

Heparin is prescribed for the prevention and treatment of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE). It is also used in the management of acute coronary syndromes (ACS), atrial fibrillation, and disseminated intravascular coagulation (DIC). It is utilized during procedures such as cardiopulmonary bypass and to maintain patency of indwelling intravenous devices. Heparin’s pharmacological classification is as an anticoagulant. It works by accelerating the action of antithrombin III, which inhibits coagulation factors, primarily thrombin (Factor IIa) and Factor Xa.

Alternate Names

Heparin is sometimes referred to as unfractionated heparin (UFH) to distinguish it from low-molecular-weight heparin (LMWH). Brand names can vary depending on the country.

How It Works

Pharmacodynamics: Heparin binds to antithrombin III (ATIII), enhancing its activity. This leads to the inactivation of thrombin and Factor Xa, preventing the formation of fibrin clots and reducing thrombus propagation.

Pharmacokinetics:

• Absorption: Heparin is not absorbed orally and must be administered parenterally (IV, subcutaneous). Intravenous administration results in immediate anticoagulant effect. Subcutaneous administration has a delayed onset of action (1-2 hours).
• Metabolism: Some metabolism occurs in the liver.
• Elimination: Primarily renal elimination, but a significant portion is cleared by the reticuloendothelial system (RES). The half-life is dose-dependent.

Mode of Action: Heparin’s primary mode of action is through ATIII-mediated inhibition of coagulation factors. It does not directly lyse existing clots but prevents their growth and extension.

Receptor Binding/Enzyme Inhibition: Heparin binds to ATIII, acting as a cofactor to potentiate its inhibitory activity against thrombin and Factor Xa.

Elimination Pathways: Heparin is cleared through renal excretion and metabolism by the RES.

Dosage

Heparin dosing is weight-based and must be individualized based on clinical indication, patient response (monitoring aPTT), and bleeding risk.

Standard Dosage

Adults:

• VTE treatment:
  • IV bolus: 80 units/kg, followed by continuous infusion of 18 units/kg/hr
  • OR: 5000 unit IV bolus, followed by a continuous infusion of 1300 units/hour. Dosage adjustments are made according to aPTT results.
  • Alternatively: Initial subcutaneous injection of 250 units/kg followed by 250 units/kg every 12 hours
• VTE prophylaxis: 5000 units subcutaneously every 8-12 hours.

Children:

• Neonates (for anticoagulation): Loading dose: 75 units/kg IV over 10 minutes followed by a maintenance dose of 28 units/kg/hour by continuous IV infusion.
• Infants: 25–30 units/kg/hour IV infusion (infants < 2 months have higher requirements).
• Children > 1 year: 18–20 units/kg/hour IV infusion (older children may require less). Dosage should be titrated based on aPTT monitoring.

Special Cases:

• Elderly Patients: Start with lower doses and titrate cautiously due to increased bleeding risk.
• Patients with Renal Impairment: Dose reduction is required for patients with creatinine clearance (CrCl) < 30 ml/min.
• Patients with Hepatic Dysfunction: Use with caution. Dose adjustment may be needed.
• Patients with Comorbid Conditions: Adjustments may be needed depending on specific conditions and bleeding risk.

Clinical Use Cases

Dosing is generally weight-based and guided by aPTT monitoring. Specific guidelines for various clinical use cases are available, but some examples include:

• Intubation, Surgical Procedures, Mechanical Ventilation, Intensive Care Unit (ICU) Use: Heparin is often used for DVT prophylaxis (5000 units subcutaneously every 8-12 hours or adjusted for renal impairment). Therapeutic dosing for established thrombosis follows weight-based protocols.
• Emergency Situations (e.g., ACS): Weight-based bolus and continuous infusion based on the specific condition and use of other antiplatelet agents (e.g., GPIIb/IIIa inhibitors).

Dosage Adjustments

Dose modifications are essential based on aPTT monitoring, renal/hepatic function, patient weight, and concomitant medications.

Side Effects

Common Side Effects:

• Bleeding (minor or major)
• Bruising
• Pain at injection site
• Itching
• Rash

Rare but Serious Side Effects:

• Heparin-induced thrombocytopenia (HIT)
• Severe bleeding (internal or external)
• Allergic reactions (anaphylaxis)
• Osteoporosis (with long-term use)

Long-Term Effects:

Osteoporosis can occur with prolonged high-dose heparin use.

Adverse Drug Reactions (ADR): HIT and severe bleeding require immediate discontinuation of heparin and alternative anticoagulation strategies.

Contraindications

• Active major bleeding
• Severe thrombocytopenia
• History of HIT
• Hypersensitivity to heparin

Drug Interactions

• Antiplatelet agents (e.g., aspirin, clopidogrel): Increased bleeding risk.
• NSAIDs: Increased bleeding risk.
• Warfarin: Close monitoring is required when transitioning between heparin and warfarin.

Pregnancy and Breastfeeding

Heparin does not cross the placenta and is generally considered safe to use during pregnancy. It is also considered safe during breastfeeding.

Drug Profile Summary

• Mechanism of Action: Accelerates antithrombin III activity, inhibiting thrombin and Factor Xa.
• Side Effects: Bleeding, bruising, HIT, osteoporosis.
• Contraindications: Active bleeding, thrombocytopenia, HIT history.
• Drug Interactions: Antiplatelet agents, NSAIDs, warfarin.
• Pregnancy & Breastfeeding: Generally safe.
• Dosage: Weight-based and individualized.
• Monitoring Parameters: aPTT, platelet count.

Popular Combinations

Heparin is often used in combination with antiplatelet agents (e.g., aspirin) in the setting of ACS.

Precautions

Close monitoring of aPTT and platelet count is essential. Patients should be educated about signs and symptoms of bleeding.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Heparin?

A: Heparin dosage is weight-based and depends on the indication. Therapeutic doses are generally higher than prophylactic doses. aPTT monitoring is essential for dose adjustments.

Q2: How is Heparin administered?

A: Heparin is administered intravenously (continuous infusion or intermittent bolus) or subcutaneously.

Q3: What are the major side effects of Heparin?

A: The most significant side effect is bleeding. Heparin-induced thrombocytopenia (HIT) is a rare but serious complication.

Q4: What is Heparin-induced thrombocytopenia (HIT)?

A: HIT is an immune-mediated reaction that causes a drop in platelet count and an increased risk of thrombosis.

Q5: What are the contraindications to using Heparin?

A: Contraindications include active major bleeding, severe thrombocytopenia, and history of HIT.

Q6: How is Heparin monitored?

A: aPTT is used to monitor the therapeutic effect of heparin. Platelet counts should also be monitored regularly for HIT.

Q7: What is the antidote for Heparin overdose?

A: Protamine sulfate can reverse the anticoagulant effects of heparin.

Q8: Can Heparin be used during pregnancy?

A: Heparin is considered safe to use during pregnancy as it does not cross the placenta.

Q9: What is the difference between unfractionated heparin (UFH) and low molecular weight heparin (LMWH)?

A: UFH has a longer chain length and more variable bioavailability compared to LMWH. LMWH has a more predictable anticoagulant response and can often be given in fixed doses without aPTT monitoring.

Q10: How is Heparin used in the setting of acute coronary syndrome (ACS)?

A: Heparin is used in ACS, often in combination with antiplatelet agents, to prevent clot formation and reduce the risk of further cardiac events. Dosing depends on the specific situation (e.g. presence of GPIIb/IIIa inhibitor use).