Key result
Unfractionated heparin, but not low-molecular-weight heparin, is associated with progressive depletion of tissue factor pathway inhibitor, potentially explaining the superior efficacy of LMWH.
Differential depletion of TFPI by UFH versus LMWH provides a mechanistic explanation for the superior efficacy of LMWH observed in clinical trials.
May support LMWH preference via TFPI preservation; hypothesis-generating and leaves open need for outcome trials.
Tissue factor pathway inhibitor (TFPI) is now recognized as a major physiological anticoagulant. Its main role is to modulate factor VIIa/tissue factor catalytic activity. Another important role is to potentiate the effect of heparins. TFPI is released from the vascular endothelium after injection of either unfractionated heparin (UFH) or low-molecular-weight heparins (LMWHs), which may then provide high concentrations of TFPI at sites of tissue damage and ongoing thrombosis. In dilute prothrombin-time-based assays, released TFPI contributes approximately one-third to the anticoagulant effect of heparin, the remaining being accounted for by antithrombin. Released TFPI, but not plasma TFPI, contains the basic carboxy-terminal tail which is important for the anticoagulant effect. UFH and LMWH exert differential effects on intravascular TFPI. UFH, but not LMWH, given in therapeutic doses, is associated with a progressive depletion of TFPI, which is associated with a strong rebound activation of coagulation after cessation of treatment. Such depletion may explain the apparent superior efficacy of LMWH observed in clinical trials.
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Sandset et al. (2000) reported a review. Heparins (UFH and LMWH) was evaluated. Unfractionated heparin, but not low-molecular-weight heparin, is associated with progressive depletion of tissue factor pathway inhibitor, potentially explaining the superior efficacy of LMWH.
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