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Post-transcriptional, post-translational and pharmacological regulation of tissue factor pathway inhibitor

Subramaniam, Saravanana,b; Kanse, Sandip M.c; Kothari, Hemad; Reinhardt, Christophe; Fletcher, Craigb

Blood Coagulation & Fibrinolysis: December 2018 - Volume 29 - Issue 8 - p 668–682
doi: 10.1097/MBC.0000000000000775
REVIEW ARTICLES
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Tissue factor (TF) pathway inhibitor (TFPI) is an endogenous natural anticoagulant that readily inhibits the extrinsic coagulation initiation complex (TF-FVIIa-Xa) and prothrombinase (FXa, FVa and calcium ions). Alternatively, spliced TFPI isoforms (α, β and δ) are expressed by vascular and extravascular cells and regulate thrombosis and haemostasis, as well as cell signalling functions of TF complexes via protease-activated receptors (PARs). Proteolysis of TFPI plays an important role in regulating physiological roles of the TF pathway in host defense and possibly haemostasis. Elimination of TFPI inhibition has therefore been proposed as an approach to improve haemostasis in haemophilia patients. In this review, we focus on posttranscription and translational modification of TFPI and its function in thrombosis and how pharmacological inhibitors and endogenous proteases interfere with TFPI and alter haemostasis.

aBlood Research Institute, BloodCenter of Wisconsin, Milwaukee

bDepartment of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

cOslo University Hospital and University of Oslo, Oslo, Norway

dDivision of Cardiovascular Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, USA

eCenter for Thrombosis and Hemostasis (CTH), University Medical Center Mainz, Johannes Gutenberg University, Mainz, Germany

Correspondence to Saravanan Subramaniam, PhD, Blood Research Institute, BloodCenter of Wisconsin, Milwaukee-53226, USA E-mail: saravanan.subramaniam@BCW.edu

Received 21 July, 2018

Accepted 6 September, 2018

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