Heparins and fondaparinux
Thrombin · detail · Via antithrombin Anti-Xa Safe in pregnancy
Heparin has no anticoagulant activity of its own: its pentasaccharide sequence binds antithrombin and induces a conformational change that accelerates inhibition of factor Xa and thrombin more than a thousand-fold. Chain length decides the target, because only chains of at least 18 saccharides are long enough to bridge antithrombin to thrombin — so LMWH and fondaparinux act almost purely on factor Xa.
Traced from the start
- Tissue factor and the extrinsic triggerVitamin K cycle and gamma-carboxylation
- Contact activation system (factor XII, prekallikrein, high-molecular-weight kininogen)
- Subendothelial collagen and von Willebrand factor
- Tissue factor-factor VIIa complex (extrinsic tenase)Factor IXaFactor VIIIa and its von Willebrand factor carrierActivated platelet phospholipid surface
- Factor Xa
- Heparins and fondaparinux
Detail
- Unfractionated heparin
- Anti-Xa to anti-IIa activity 1:1; monitored by APTT ratio or anti-Xa; half-life about 1 hour; fully reversed by protamine sulfate
- LMWH
- Enoxaparin and dalteparin: anti-Xa to anti-IIa about 3-4:1, subcutaneous and predictable, renally cleared; anti-Xa monitoring only in pregnancy, extremes of weight or renal impairment; only partially reversed by protamine
- Fondaparinux
- Synthetic pentasaccharide with pure anti-Xa activity; no protamine reversal; usable in heparin-induced thrombocytopenia
- Pregnancy
- Heparins do not cross the placenta, making LMWH the anticoagulant of choice in pregnancy
When it goes wrong
Heparin-induced thrombocytopenia, considerably more common with unfractionated than low-molecular-weight heparin
Thrombocytopenia with venous or arterial thrombosis 5-10 days after first exposure; score with the 4Ts, confirm with anti-PF4 antibodies and a functional assay
LMWH given at treatment dose in significant renal impairment, or prolonged heparin therapy
Accumulation and bleeding; long-term heparin also causes osteoporosis and hyperkalaemia through aldosterone suppression
Practise this structure
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