Factor V Deficiency
A number sign (#) is used with this entry because factor V deficiency, also known as parahemophilia, is caused by homozygous or compound heterozygous mutation in the gene encoding coagulation factor V (F5; 612309) on chromosome 1q24.
Clinical FeaturesOwren (1947) described a haemorrhagic diathesis, which he referred to as 'parahemophilia,' due to the absence of a previously unknown clotting factor.
Kingsley (1954) and Seibert et al. (1958) reported familial factor V deficiency in a consanguineous kindreds, indicating autosomal recessive inheritance. Seibert et al. (1958) observed consistently prolonged bleeding and clotting times in affected individuals.
Yoshioka et al. (1975) stated that 28 cases of factor V deficiency had been recorded in Japan.
Mitterstieler et al. (1978) reported a 14-month-old girl with a tendency toward heavy bleeding caused by severe isolated congenital factor V deficiency. Ten of 56 examined family members had factor V levels ranging from 26 to 60% of normal; these were classified as heterozygotes. The case histories of the heterozygotes did not reveal a bleeding tendency. Mitterstieler et al. (1978) concluded that the inheritance of this factor V deficiency is autosomal recessive, with varying expressivity in heterozygotes.
Chiu et al. (1983) identified 4 individuals with factor V deficiency and a variant form of the factor V molecule that reacted with a polyclonal rabbit antibody, but not with the naturally occurring antibody. In all, 14 patients with congenital factor V deficiency were studied. In 10, factor V antigen and coagulant activity were both decreased compared to controls.
Fischer et al. (1984) found an inbred Brazilian kindred, located because 2 affected persons had the same surname, with multiple cases of isolated factor V deficiency.
Ehrenforth et al. (1998) described severe factor V deficiency presenting as a subdural hematoma in the newborn.
Guasch et al. (1998) reported a girl, born of consanguineous parents, who presented at age 3 years with prolonged bleeding from a cut in her upper lip after trauma. Routine clotting tests showed prolonged activated partial thromboplastin time (aPTT) and prothrombin time (PT). Essentially no plasma factor V activity or antigen could be detected in plasma. At age 7 years, she had never had a bleed that necessitated therapy, although minor injuries sometimes resulted in prolonged bleeding. Her only other symptom was easy bruising. The patient's father had undergone many surgical procedures without any bleeding complications, but her mother had excessive bleeding after tooth extractions and childbirth. aPTTs and PTs of the parents were within the normal range.
Van Wijk et al. (2001) reported a 19-year-old Korean woman with severe factor V deficiency. She developed bleeding of the soft tissue of the mouth at the age of 19 months, experienced a large subdural hematoma at the age of 4 years, and suffered soft tissue bleeds of the mouth, epistaxis, and hematomas for which she received fresh frozen plasma once every 3 months. In recent years her bleeding pattern changed to spontaneous muscle bleedings.
Van Wijk et al. (2001) also reported a 15-year-old girl from Morocco, the daughter of first-cousin parents, with severe factor V deficiency with F5 activity less than 1%. The patient was identified in the course of family screening. A 23-year-old brother, previously described by Tanis et al. (1998), also had severe factor V deficiency and prolonged bleeding after injuries. Both patients were homozygous for a mutation in the F5 gene (612309.0008)
Molecular GeneticsIn a patient with factor V deficiency, Guasch et al. (1998) identified a homozygous mutation in the F5 gene (612309.0004).
In a Korean woman with factor V deficiency, van Wijk et al. (2001) identified compound heterozygosity for 2 mutations in the F5 gene (612309.0006; 612309.0007).
Population GeneticsZehnder et al. (1999) pointed out that homozygous factor V deficiency is rare, approximately 1 in a million. On this basis, heterozygotes should have a frequency of 1 in 1,000. Heterozygous deficiency states are generally unrecognized because of a lack of significant clotting time prolongation or bleeding risk.
HistoryHurtubise et al. (1979) isolated an immunoglobulin with the characteristics of a monoclonal antibody against factor V from the serum of a patient with a fatal hemorrhagic diathesis.