USP Standard 99% Heparin sodium CAS 9041-08-1 Anticoagulant Drug from bovine source

Heparin Sodium More Info

Heparin sodium is a widely used anticoagulant belonging to the glycosaminoglycan class, primarily employed to prevent and treat blood clots.

Mechanism of Action

Heparin sodium exerts its anticoagulant effect by binding to antithrombin III (ATIII), a natural inhibitor of several activated clotting factors. This binding induces a conformational change in ATIII, significantly accelerating its ability to inactivate thrombin (factor IIa), factor Xa, and other proteases involved in coagulation such as factors IXa, XIa, and XIIa. The inactivation of thrombin requires formation of a ternary complex involving heparin, ATIII, and thrombin, which depends on heparin chains of at least 18 saccharide units. In contrast, inhibition of factor Xa requires only the specific pentasaccharide sequence within heparin. By enhancing ATIII activity, heparin prevents the conversion of fibrinogen to fibrin, thereby inhibiting clot formation and extension. Heparin itself is not thrombolytic; it does not dissolve existing clots but prevents new clot formation and growth.

Applications

Heparin sodium is indicated for:
Prophylaxis and treatment of venous thromboembolism (deep vein thrombosis, pulmonary embolism).
Prevention of clotting in atrial fibrillation with embolization risk.
Treatment of disseminated intravascular coagulation (DIC).
Prevention of clot formation during arterial and cardiac surgery.
Prophylaxis and treatment of peripheral arterial embolism.
Anticoagulation during blood transfusions, extracorporeal circulation (e.g., cardiopulmonary bypass), and dialysis procedures.

Routes of Administration

Intravenous (IV) Injection or Infusion: For rapid anticoagulation in acute settings.
Subcutaneous (SC) Injection: For prophylaxis and maintenance therapy.
Oral: Not effective due to poor absorption; however, experimental oral formulations with absorption enhancers have been studied.
Avoid Intramuscular Injection: Due to risk of hematoma formation.
Heparin sodium is usually administered by deep subcutaneous injection in the abdomen or arm using fine needles to minimize tissue trauma.

Pharmacokinetics

Absorption: Rapid and nearly complete after IV administration; subcutaneous absorption is slower and more variable.
Distribution: Widely distributed in plasma and extracellular fluid.
Metabolism: Primarily cleared by the reticuloendothelial system and partially by renal excretion.
Elimination Half-life: Approximately 1 to 2 hours, depending on dose and route.
Monitoring: Requires frequent monitoring of activated partial thromboplastin time (aPTT) to maintain therapeutic anticoagulation.
Oral bioavailability: Poor, but novel oral formulations with absorption enhancers (e.g., SNAC) have demonstrated measurable plasma levels and anticoagulant effects in clinical studies.

Safety and Side Effects

Common Side Effects:
Bleeding and bruising, including prolonged bleeding time.
Injection site reactions such as pain, irritation, and hematoma.
Elevated liver enzymes.
Serious Side Effects:
Severe bleeding, which may manifest as unusual bruising, nosebleeds, blood in urine or stool, coughing or vomiting blood.
Heparin-induced thrombocytopenia (HIT), an immune-mediated reduction in platelet count that paradoxically increases risk of thrombosis.
Allergic reactions including rash, hives, fever, chills, and in rare cases, anaphylaxis.
Skin necrosis at injection sites.
Precautions:
Use cautiously in patients with bleeding disorders, severe hypertension, or recent surgery.
Avoid intramuscular injections.
Monitor platelet counts regularly to detect HIT early.
Pregnancy category C; used when benefits outweigh risks.
Reversal: Effects of heparin can be reversed by protamine sulfate administration in cases of overdose or excessive bleeding.

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