1. Effects of heparin include interaction with Antithrombin 3, charge dependent interaction, and modulation of factor Xa generation. The low affinity for AT3 leads to greater effect when it binds PF4, which may lead to heparin antibodies (IgG) which activate platelets and lead to HIT. Heparin also binds to plasma proteins, macrophages, and endothelial cells, causes increased vessel wall permeability, and supression of smooth muscle proliferation, and activation of osteoclasts. It can be reversed with protamine, 1 mg per 100 units of UFH received over several hours.
Pearls on HIT
arterial OR venous clots occur
AB's against Factor 4 platelets complexes PF$ and heparin
10X more common with heparin than with LMWH
Mechanisms of heparin: binds tissue factor and F VIIa at site of injury. Inhibits propagation of clot when F IXa binds to coafactor, and F VIIIa (intrinsic pathway)
2. LMWH's preferentially inactivate Xa with less HIT, and has a more predictable dose response relationship due to decreased binding to endothelial cells, proteins and macrophages. Protamine neutralizes only 60 % of anti Xa activity of LMWH's.
3. Prothrombin time (PT) to monitor VKA's is performed by adding calcium and thromboplastin to citrated plasma. INR is international normalized ratio where = (patient P/mean normal PT)*ISI (international sensitivity index).
4. Ximelegatran can use fixed dose, has no food or drug interactions,
Heparin, LMWH are indirect thrombin inhibitors
hirudin, argabotan, inactivate bound thrombin and are direct inhibitors
Pearls on HIT
arterial OR venous clots occur
AB's against Factor 4 platelets complexes PF$ and heparin
10X more common with heparin than with LMWH
Mechanisms of heparin: binds tissue factor and F VIIa at site of injury. Inhibits propagation of clot when F IXa binds to coafactor, and F VIIIa (intrinsic pathway)
2. LMWH's preferentially inactivate Xa with less HIT, and has a more predictable dose response relationship due to decreased binding to endothelial cells, proteins and macrophages. Protamine neutralizes only 60 % of anti Xa activity of LMWH's.
3. Prothrombin time (PT) to monitor VKA's is performed by adding calcium and thromboplastin to citrated plasma. INR is international normalized ratio where = (patient P/mean normal PT)*ISI (international sensitivity index).
4. Ximelegatran can use fixed dose, has no food or drug interactions,
Heparin, LMWH are indirect thrombin inhibitors
hirudin, argabotan, inactivate bound thrombin and are direct inhibitors
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