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Factor Va

Common pathway · Cofactor APC target Factor V Leiden

Factor V circulates in plasma and in platelet alpha granules and is cleaved to Va by thrombin and by factor Xa. It has no enzymatic activity of its own — it is the cofactor that anchors Xa on the phospholipid surface and orients prothrombin for cleavage. Activated protein C destroys it by cleaving at Arg506, Arg306 and Arg679.

Traced from the start

  1. Subendothelial collagen and von Willebrand factor
  2. Activated platelet phospholipid surface
  3. Factor Va

Detail

Role
Non-enzymatic cofactor of prothrombinase; not vitamin K dependent
Activated by
Thrombin, in a positive feedback loop, and by factor Xa
Inactivated by
Activated protein C, with protein S as its cofactor
Source
Liver and megakaryocytes; about a fifth of circulating factor V is carried inside platelet alpha granules and released at the site of injury

When it goes wrong

Factor V Leiden — an Arg506Gln substitution that removes an activated protein C cleavage site

Activated protein C resistance and the commonest inherited thrombophilia in people of European descent (about 5% heterozygous); roughly 5-fold venous thrombosis risk when heterozygous, and much higher again on the combined oral contraceptive pill

Combined factor V and factor VIII deficiency from an LMAN1 or MCFD2 mutation in the shared secretory chaperone

Both PT and APTT prolonged with mild bleeding — the exception to the rule that factor V and factor VIII deficiencies are unrelated diseases

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