Factor V Deficiency
Factor V is synthesized by the liver and circulates in plasma as an inactive procoagulant until it is activated by either thrombin or activated Factor X. Approximately 25% of factor V is stored within the alpha granules of platelets. Activated factor V serves as a cofactor for FXa in the prothrombinase complex to convert prothrombin to thrombin on the surface of platelets.
Congenital factor V deficiency is a rare autosomal recessive disorder with a prevalence of 1 case per 1 million people. Approximately 75% of cases have a quantitative deficiency while 25% have a qualitative defect. Some patients may have a very rare combined deficiency of factor V and factor VIII that is inherited as an autosomal recessive loss of the LMAN1 gene. This gene encodes a carrier protein that transports FV and FVIII from the endoplasmic reticulum to the Golgi apparatus for secretion into the vasculature.
In addition to inherited deficiencies, some patients develop acquired factor V inhibitors. Previously, development of factor V inhibitors was often associated with exposure to bovine thrombin used for topical hemostasis. Antibodies directed against residual bovine factor V in bovine thrombin products cross-reacted with human factor V. Advancements in preparation of topical thrombin have reduced the incidence of antibody formation. Factor V inhibitors can also occur in association with autoimmune disorders, malignancy, infections and antibiotic use.
Patients with congenital factor V deficiency and factor V activity above 15% are often asymptomatic and are identified after finding prolonged prothrombin time and activated plasma thromboplastin time. Patients with congenital factor V deficiency and factor V levels less than 10% may present with a variety of symptoms ranging from epistaxis and oral mucosal bleeding to hemarthrosis, menorrhagia, soft tissue hematoma or CNS hemorrhage. Patients with acquired inhibitors are more likely to present with bleeding, probably because the autoantibodies inhibit both plasma and platelet-associated factor V.
Plasma transfusion is often used to treat bleeding due to factor V deficiency. A loading dose of 20 mL per kg of body weight followed by a maintenance dose of 5 mL per kg every 12 hours may be needed for severe bleeding. Another option is to treat bleeding patients with platelet transfusions. Platelet transfusions are often more effective than plasma, especially in patients with inhibitors.
