What is the role of TF pathway inhibitor (TFPI) in the pathophysiology of disseminated intravascular coagulation (DIC)?

Updated: Dec 06, 2020
  • Author: Marcel M Levi, MD; Chief Editor: Srikanth Nagalla, MBBS, MS, FACP  more...
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Answer

TF pathway inhibitor (TFPI) is another anticoagulant mechanism that is disabled in DIC. TFPI reversibly inhibits factor Xa and thrombin (indirectly) and has the ability to inhibit the TF-VIIa complex. Although levels of TFPI are normal in patients with sepsis, a relative insufficiency in DIC is evident. TFPI depletion in animal models predisposes to DIC, and TFPI blocks the procoagulant effect of endotoxin in humans. [29] The role of TFPI in the pathogenesis of DIC has not been fully clarified.

The experimental finding that administration of recombinant TFPI blocks inflammation-induced thrombin generation in humans, along with the observation that pharmacologic doses of TFPI are capable of preventing mortality during systemic infection and inflammation, suggests that high concentrations of TFPI are capable of modulating TF-mediated coagulation. Presumably, however, the endogenous concentration of TFPI is insufficiently capable of regulating coagulation activation and the downstream consequences during systemic inflammation.


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