Advances in understanding the bleeding diathesis in factor V deficiency

Abstract

SummaryCoagulation factor V (FV), present in plasma and platelets, is an indispensable clotting factor, as demonstrated by the uniform lethality of FV knock-out mice. Surprisingly, however, severe FV deficiency is rarely fatal in humans. In fact, although several cases of life-threatening intracranial haemorrhage have been reported in FV-deficient newborns, many patients with undetectable FV levels experience only mild to moderate bleeding and do not require routine prophylaxis. While the reasons for this variable phenotypic expression are largely unknown, several observations from different laboratories indicate platelets as crucial players in FV deficiency. Moreover, we have recently shown that plasma levels of tissue factor pathway inhibitor are considerably reduced in FV-deficient plasma, which results in enhanced thrombin generation especially at very low FV levels (<2%). The present review discusses and integrates these findings in the context of the biology of FV and the clinical features of FV deficiency.

A Bipartite Autoinhibitory Region within the B-domain Suppresses Function in Factor V

“…Arg 372 and Arg 1689 ) that alter the rate and/or extent of FVIII activation and cause hemophilia A. Although FV deficiency is rarer, there are no known missense mutations for FV that alter its activation (56). We speculate that because there are multiple routes to disrupt the PRR, a single amino acid change would unlikely be so unfavorable as to substantially impact FV activation.…”

Congenital Factor V Deficiency: Moroccans Cases

“…However, its prevalence may be underestimated because mild cases are often overlooked [1,3,4]. This deficiency is due to an autonomic recessive transmission, it is more common in countries where consanguineous marriages are common, which is the case in our country.…”

Persistant Hemothorax after Video-Assisted Thoracoscopic Surgery Secondary to Factor V Deficiency

“…In many countries were consanguineous marriages occur, the congenital form is genetically transmitted as an autonomic recessive pattern, as seen in Iran, where this coagulation disorder occurs 10 times that seen in the western civilization [10] but has also been reported in Italy, USA and Canada [9]. Acquired deficiency associated with Factor V inhibition has been reported in hepatic dysfunction [11], antibiotics such as cefuroxime or metronidazole [12], β-lactamase production [13], and autoimmune diseases are the most common etiologies and, the excessive administration of protamine [14] and tuberculosis [15] being less frequent.…”

“…Factor V deficiencies are classified as 1) Congenital (Owren parahemophilia), 2) Combined Factor V and Factor VIII deficiency, 3) Acquired due to severe hepatic disease or disseminated intravascular coagulopathy and more commonly, secondary to the development of Factor V inhibitors, i.e. antibodies that bind to Factor V and promote its degradation and/or block its activity, and 4) Platelet Factor V deficiency [9].…”

“…Factor V plays an important role in the anticoagulant pathway because its inactivated form participates in the inactivation of factor VIIIvia activated protein C (APC). It has a dual action as a procoagulant, with mutations, predisposing to thrombosis [3] and as an anticoagulant, with its deficiency being associated to variable severity of bleeding tendencies depending on the Factor V level [9]. Factor V deficiencies are classified as 1) Congenital (Owren parahemophilia), 2) Combined Factor V and Factor VIII deficiency, 3) Acquired due to severe hepatic disease or disseminated intravascular coagulopathy and more commonly, secondary to the development of Factor V inhibitors, i.e.…”