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Blood coagulation factor X: molecular biology, inherited disease, and engineered therapeutics

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Abstract

Blood coagulation factor X/Xa sits at a pivotal point in the coagulation cascade and has a role in each of the three major pathways (intrinsic, extrinsic and the common pathway). Due to this central position, it is an attractive therapeutic target to either enhance or dampen thrombin generation. In this brief review, I will summarize key developments in the molecular understanding of this critical clotting factor and discuss the molecular basis of FX deficiency, highlight difficulties in expressing recombinant factor X, and detail two factor X variants evaluated clinically.

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Abbreviations

TF:

Tissue factor

FX:

Factor X

FXa:

Factor Xa

FVIIa:

Factor VIIa

FIXa:

Factor IXa

FVIIIa:

Factor VIIIa

FVa:

Factor Va

rFX:

Recombinant factor X

Gla:

Gamma-carboxyglutamic acid

EGF:

Epidermal growth factor

RVV-X:

Factor X activating enzyme from Vipiera russulli

CHO:

Chinese hamster ovary

HEK:

Human embryonic kidney

DOAC:

Direct oral anticoagulants

aPCC:

Activated prothrombin complex concentrates

TFPI:

Tissue factor pathway inhibitor

wt:

Wild-type

aPTT:

Activated partial thromboplastin time

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Funding

This study was supported by National Heart, Lung, and Blood Institute (Grant Numbers: U54 HL142012, Project 4 and P01 HL139420, Project 2).

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Authors and Affiliations

  1. Division of Hematology and the Raymond G. Perelman Center for Cellular and Molecular Therapeutics, The Children’s Hospital of Philadelphia, Philadelphia, PA, 19104, USA

    Rodney M. Camire

  2. Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Rodney M. Camire

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Correspondence to Rodney M. Camire.

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RMC is a consultant for and receives research support from Pfizer and Bayer. RMC also receives licensing fees for technology related to zymogen-like FXa.

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Camire, R.M. Blood coagulation factor X: molecular biology, inherited disease, and engineered therapeutics. J Thromb Thrombolysis 52, 383–390 (2021). https://doi.org/10.1007/s11239-021-02456-w

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