Which anticoagulants are being investigated as possible treatments for protein S deficiency?

Updated: Jan 03, 2021
  • Author: Mohammad Muhsin Chisti, MD, FACP; Chief Editor: Perumal Thiagarajan, MD  more...
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Answer

Agents in the following classes are under development:

  • Tissue factor pathway inhibitor (TFPI)  –  TFPIs act in two ways: by directly inhibiting factor Xa and by forming a complex together with factor Xa that inhibits tissue factorTF/factor VIIa. Currently the recombinant form is being tested.
  • Factor VIII inhibitor – With an approximate 3-week half-life, TB-402 is a human IgG4 monoclonal antibody with a partial inhibitor activity. TB-402 has been found to be effective for a 10 days equivalent of LMWH in a randomized phase II trial in patients who have undergone total knee replacement.
  • Factor IXa inhibitor  – REG1 has two components: RB006, which binds and inhibits factor IXa; and RB007, which neutralizes its anti-IXa activity. Trials are still underway to determine its effect when combined with anit-platelet therapy in patients with coronary artery disease.
  • Factor XI inhibitor  – FXI-ASO is a factor XI antisense oligonucleotide that potentially reduces factor XI.
  • Factor XIIa inhibitor  – rHA-Infestin-4 is a factor XIIa inhibitor that is being investigated in the management of acute ischemic cardiovascular and cerebrovascular events.
  • Polyphosphate inhibitors  – Platelets, when activated, release polyphosphate, which impacts coagulation via the intrinsic pathway. Compounds that inhibit polyphosphate are being investigated.
  • Thrombomodulin  –  ART-123 is the recombinant part of the extracellular domain of thrombomodulin. It has been approved in Japan for the treatment of disseminated intravascular coagulation. It has a plasma half-life of 2-3 days and can be administered subcutaneously every five to six days.

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