Inherited and acquired factor V deficiency

Abstract

The clotting factor V, also known as proaccelerin or labile factor, is synthesized by the liver and possibly by the megakaryocytes. Factor V exerts a pivotal role in hemostasis, as it participates in both procoagulant and anticoagulant pathways, being an essential cofactor of the prothrombinase complex in the former case and participating in the inactivation of factor VIII (FVIII) in the latter. Isolated factor V deficiency due to mutations in the F5 gene is a rare inherited coagulopathy typically associated with a broad spectrum of bleeding symptoms, ranging from easy bruising, delayed bleeding after haemostatic challenges such as trauma or surgery to more severe joint bleeds. The combined deficiency of factor V and FVIII, commonly known as F5F8D, is a recessive disorder not attributable to the association of isolated factor V and FVIII deficiencies, but rather to defective intracellular processing of both proteins due to mutations involving the LMAN1 and MCFD2 genes, which encode two proteins forming an essential cargo receptor complex. Overall, patients affected by F5F8D do not bleed more in terms of both frequency and severity than those carrying specific deficiencies of both factors and the bleeding phenotype is generally mild. Although now increasingly rare, inhibitors directed against factor V may also develop in individuals of any age and are characterized by a very heterogeneous clinical phenotype. The aim of the current review is to provide an overview on the physiopathology, diagnostics, and clinical management of both inherited and acquired factor V deficiency.

Rare Bleeding Disorders in Children: Identification and Primary Care Management

“…Combined FV/FVIII deficiency exists due to a common molecular defect affecting intracellular processing of both proteins, rather than coincident defects in the genes for both factors. 60 This condition is associated with a mild bleeding phenotype, without any apparent cumulative effect of the combined deficiencies. 60 In contrast, VKCFD is often associated with significant bleeding.…”

“…60 This condition is associated with a mild bleeding phenotype, without any apparent cumulative effect of the combined deficiencies. 60 In contrast, VKCFD is often associated with significant bleeding. 31 VKCFD results from inherited defects in activation (g-carboxylation) of the vitamin K-dependent factors (FII, FVII, FIX, and FX).…”

Congenital Factor V Deficiency: Comparison of the Severity of Clinical Presentations among Patients with Rare Bleeding Disorders

“…Congenital factor V deficiency (FVD) is a rare bleeding disorder (RBD) with an estimated incidence of 1 in 1,000,000 in the general population and is inherited with an autosomal recessive pattern [2,3]. This disorder is characterized by low or undetectable plasma FV levels leading to mild to severe bleeding complications [3].…”

“…This factor has 40% identity with FVIII and the only FV domain that has no important similarity with FVIII is the B domain. FV takes part in the coagulation cascade as a nonenzymatic cofactor for the prothrombinase complex [2]. In addition, it has an essential role in downregulation of coagulation FVIII by enhancing the effect of activated protein C and therefore participates in both the pro- and anticoagulant pathway [3].…”

Acquired factor V inhibitor in a woman following aortic aneurysm surgery

“…This abnormality is diagnosed on the basis of abnormal coagulation laboratory tests, including prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT), which are not corrected in the mixing tests [2]. Acquired inhibitor may reduce the FV activity to undetectable levels [3].…”