Pharmacology  ·  Coagulation

Heparins and Indirect Thrombin Inhibitors

Mechanism, monitoring, heparin-induced thrombocytopenia, and reversal at a glance

• All heparin-based anticoagulants work by binding antithrombin III and accelerating its inhibitory activity — but chain length determines which targets are reached: long chains bridge antithrombin III to thrombin for dual inhibition, while short chains and the synthetic pentasaccharide fondaparinux inhibit factor Xa only.
• Unfractionated heparin has nonlinear, saturable pharmacokinetics with extensive nonspecific protein binding, making activated partial thromboplastin time monitoring mandatory; low-molecular-weight heparins have linear, predictable kinetics and require anti-factor Xa monitoring only in special populations.
• Heparin-induced thrombocytopenia is a prothrombotic immune syndrome — not simply low platelets — in which IgG antibodies to the platelet factor 4-heparin complex activate platelets and generate a thrombin burst, producing thrombocytopenia paradoxically accompanied by arterial and venous thrombosis.
• The 4T score is the validated pretest probability tool: a score of 6 to 8 mandates stopping all heparin immediately and starting an alternative anticoagulant empirically before laboratory results return; low-molecular-weight heparin is not an alternative because it cross-reacts in approximately 90% of cases.
• Protamine sulfate fully reverses unfractionated heparin and partially reverses low-molecular-weight heparin anti-factor Xa activity; fondaparinux has no approved reversal agent. Argatroban is the preferred alternative anticoagulant in heparin-induced thrombocytopenia with renal failure; bivalirudin is preferred with hepatic failure or when rapid offset is needed for cardiac surgery.