Factor V Deficiency

Updated: Oct 05, 2016
  • Author: Olga Kozyreva, MD; Chief Editor: Perumal Thiagarajan, MD  more...
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Overview

Background

Factor V is an essential component in the blood coagulation cascade. Inherited or acquired deficiencies in factor V are rare causes of bleeding disorders.

Factor V deficiency is also known as Owren disease. Dr. Paul Owren identified this defect in Norway in 1943. Using relatively primitive technology, he was able to deduce the existence of a fifth component required for fibrin formation, which he named factor V, thus beginning the era of Roman numerology for coagulation factors.

Dr. Owren's work defined factor V as the activity in normal plasma that corrected the prothrombin time (PT) of the plasma in a patient with factor V deficiency. Factor V deficiency has also been called parahemophilia, since hemarthrosis can occur with severe deficiencies and with increased bleeding time. [1, 2]

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Pathophysiology

Factor V is an essential component in the blood coagulation cascade. Factor V is synthesized in the liver and possibly in megakaryocytes. Factor V circulates in an inactive form. During coagulation, factor V is converted to the active cofactor, factor Va, via limited proteolysis by the serine protease a-thrombin. Factor Va and activated factor Xa form the prothrombinase complex. The prothrombinase complex is responsible for the rapid conversion of the zymogen prothrombin to the active serine protease a-thrombin. [3, 4] Thrombin cleaves fibrinogen to form fibrin, leading to the ultimate step in coagulation, the formation of a fibrin clot. [5] See images below.

Antithrombin sites of action. Antithrombin sites of action.
Cell surface-directed hemostasis. Initially, a sma Cell surface-directed hemostasis. Initially, a small amount of thrombin is generated on the surface of the tissue factor (TF)–bearing cell. Following amplification, the second burst generates a larger amount of thrombin, leading to fibrin (clot) formation. Adapted from Hoffman and Monroe, Thromb Haemost 2001, 85(6): 958-65.

Inherited factor V deficiency is a rare condition that is associated with an abnormal factor V plasma level. Acquired factor V deficiency is a rare clinical condition in which the development of antibodies to factor V (factor V inhibitors) leads to hemorrhagic complications of varying severity. The addition of normal plasma cannot correct the prolonged PT and activated partial thromboplastin time (aPTT). Factor V inhibitors can occur after surgery, childbirth, autoimmune diseases, and with certain neoplasms.

Factor V Leiden is a completely different inherited disorder that involves a single point mutation in the factor V gene. Factor V activity levels in patients with factor V Leiden are normal. [6] Proteolytic inactivation of factor Va and factor VIIIa by activated protein C (APC) normally limits clot formation; however, factor V Leiden resists inactivation by APC.

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Epidemiology

Frequency

International

Only 150 cases of congenital factor V deficiency have been reported worldwide since 1943. Homozygous factor V deficiency is rare, occurring in approximately 1 per million population.

Delev et al presented 39 German patients with factor V deficiency. [7] In 36 cases with an identifiable causative mutation, 20 patients were heterozygous for the mutation, whereas 9 were homozygous, 6 were compound heterozygous, and 1 proband was pseudohomozygous. [7] There were no mutations found in the remaining 3 patients.

The investigators identified 33 uniquely different mutations of a total 42 genetic mutations: 19 missense mutations, 8 nonsense mutations, 4 small deletions, and 2 splice site mutations. [7] Of the 33 unique mutations, 23 were novel sequence variations not previously reported, and all changes found in exon 13 led to null alleles as nonsense mutations or small deletions.

Mortality/Morbidity

The severity of factor V deficiency varies from bruising to lethal hemorrhage.

Race

No apparent racial predilection for factor V deficiency exists.

Sex

Factor V deficiency affects males and females with equal frequency.

Age

Factor V deficiency affects all ages. The age at presentation indirectly varies with the severity of disease.

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