Chap 43: Drugs in coagulation II - anticoagulants - Indirect thrombin inhibitors

INDIRECT THROMBIN INHIBITORS
- binding of antithrombin --> enhances inactivation of Xa --> reduced thrombin formation
- UFH, LMWH, synthetic fondaparinux

Heparin
- heterogenous mixture of sulfated mucopolysaccharides
- binds to endothelium + plasma proteins
- binds to antithrombin --> accelerate 1000x inactivation of clotting factors, esp IIa, IXa, Xa
- UFH - composed of high molecular weight heparin (HMWH) + LMWH

• HMWH - inhibit all 3 factors as above --> marked anticoagulants
• LMWH - inhibit activated factor X - less efx on thrombin
• but trials show that LMWH are as effective as UFH --> hence used

- HITS

• systemic hypercoagulable state
• 1-4% of ppl treated with UFH minimum 7 days
• surgical pt - high risk
• thrombosis - venous and arterial (not so common)
• suspect when - PLT dropping, having new thrombus despite heparin
• Rx with direct thrombin inhibitor/fondaparinux

- monitoring

• UFH - aPTT
• LMWH - no need as weight beight measurement, unlike UFH - but levels can be determined by anti-Xa units

- reversal of heparin action - protamine

• protamine sulfate (basic peptide) - binds to heparin --> stable complex --> no anticoagulant activity
• 1mg protamine sulfate to 100 unit of heparin
• LMWH - partial neutralisation - limited studies 1mg protamine to 1mg enoxaparin
• protamine does NOT reverse fandaparinux