Patients with severe factor V congenital deficiency (FV CD) often present during childhood with mucosal tract or umbilical stump bleeding. However, because patients with moderate FV CD tend to experience only mild symptoms, diagnosis can be delayed, often discovered during routine screening or following a surgical procedure. Because FV affects both the intrinsic and extrinsic clotting cascades, routine laboratory tests will detect prolongations in both activated partial thromboplastin time (aPTT) and prothrombin time (PT).1,2
A mixing test (1:1 with normal plasma) is necessary to exclude acquired inhibitory antibodies against coagulation factors, such as FV or FX and other anticoagulants. Patients with FV CD have reduced activity in specific FV activity PT assays. However, differential diagnosis of FV CD cannot be made until combined FV and FVIII deficiency is excluded.1-4
Combined FV and FVIII deficiency is a rare bleeding disorder caused by a defect the LMAN1 or MCFD2 genes. The proteins derived from these genes are responsible for transportation of both FV and FVIII. A defect in either gene can cause low levels of both FV and FVIII.1,2,4-6
Thus, in order to diagnose FV CD, combined FV and FVIII deficiency must be excluded using FVIII activity assays. After low FV activity is detected, FV antigen can be measured using immunological assays. Low FV activity with an approximately equal reduction in FV protein is indicative of type I FV CD, while reduced FV activity with normal FV protein levels is indicative of type II FV CD.1-5
Algorithm for the laboratory diagnosis of FV deficiency.
Initial laboratory screening
During initial laboratory screening, patients with FV CD present with prolongations of both activated partial thromboplastin time (aPTT) and prothrombin time (PT).
1:1 mixing of patient samples with normal human plasma should correct aPTT and PT in patients with FV CD. Failure of mixing to correct aPTT and PT could indicate an inhibitory antibody directed against FV or FX.
Factor activity assays
Low or immeasurable FV activity in individual factor assays indicates FV CD. However, FVIII activity assays are required confirm diagnosis and exclude combined FV and FVIII deficiency, a rare bleeding disorder with molecular mechanisms independent of FV CD or haemophilia A.
Measuring the concentration of FV antigen with a FV immunoassay can help classify FV CD as type I (low FV concentration with an equal reduction in activity) or type II (normal FV concentration with reduced activity).
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2. Asselta R, Peyvandi F. Factor V deficiency. Semin Thromb Hemost 2009;35:382-9.
3. Camire RM. A new look at blood coagulation factor V. Curr Opin Hematol 2011;18:338-42.
4. Lippi G, Favaloro EJ, Montagnana M, Manzato F, Guidi GC, Franchini M. Inherited and acquired factor V deficiency. Blood Coagul Fibrinolysis 2011;22:160-6.
5. Duckers C, Simioni P, Rosing J, Castoldi E. Advances in understanding the bleeding diathesis in factor V deficiency. Br J Haematol 2009;146:17-26.
6. Soff GA. Combined factor V and factor VIII deficiency. Clin Adv Hematol Oncol 2012;10:474-6.