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.