What is the pathophysiology of factor V deficiency?

Updated: Mar 09, 2021
  • Author: Olga Kozyreva, MD; Chief Editor: Perumal Thiagarajan, MD  more...
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Answer

Factor V is an essential component in the blood coagulation cascade. Factor V is synthesized in the liver and possibly in megakaryocytes. Factor V circulates in an inactive form. During coagulation, factor V is converted to the active cofactor, factor Va, via limited proteolysis by the serine protease a-thrombin. Factor Va and activated factor Xa form the prothrombinase complex. The prothrombinase complex is responsible for the rapid conversion of the zymogen prothrombin to the active serine protease a-thrombin. [5, 6] Thrombin cleaves fibrinogen to form fibrin, leading to the ultimate step in coagulation, the formation of a fibrin clot. [7] See images below.

Antithrombin sites of action. Antithrombin sites of action.
Cell surface-directed hemostasis. Initially, a sma Cell surface-directed hemostasis. Initially, a small amount of thrombin is generated on the surface of the tissue factor (TF)–bearing cell. Following amplification, the second burst generates a larger amount of thrombin, leading to fibrin (clot) formation. Adapted from Hoffman and Monroe, Thromb Haemost 2001, 85(6): 958-65.

Inherited factor V deficiency is a rare autosomal recessive disorder that is associated with an abnormal factor V plasma level. Numerous mutations in the F5 gene have been identified in these patients. [5, 8, 9, 10, 11, 12]  

Another rare autosomal recessive disorder, combined factor V and factor VIII deficiency, results from  mutations in either LMAN1 (lectin mannose binding–1) or MCFD2  (multiple coagulation factor deficiency gene 2). Alterations in the proteins encoded by those two genes interfere with efficient secretion of factors V and FVIII. [13]

Acquired factor V deficiency is a rare clinical condition in which the development of antibodies to factor V (factor V inhibitors) leads to hemorrhagic complications of varying severity. The addition of normal plasma cannot correct the prolonged PT and activated partial thromboplastin time (aPTT). Factor V inhibitors can occur after surgery, childbirth, use of bovine thrombin or medications, and in patients with autoimmune diseases and certain neoplasms. [14, 15]

Factor V Leiden is a completely different inherited disorder that involves a single point mutation in the factor V gene. Factor V activity levels in patients with factor V Leiden are normal. [16] Proteolytic inactivation of factor Va and factor VIIIa by activated protein C (APC) normally limits clot formation; however, factor V Leiden resists inactivation by APC. Consequently, individuals who are homozygous for factor V Leiden have a high incidence of thrombosis. For more information, see Hereditary and Acquired Hypercoagulability.


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