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Combined deficiency of factor V and factor VIII
A rare inherited bleeding disorder due to the reduction in activity and antigen levels of both factor V (FV) and factor VIII (FVIII) and characterized by mild-to-moderate bleeding symptoms.
ORPHA:35909Classification level: Disorder
Prevalence is estimated between 1/100,000 and 1/1,000,000. The condition is more prevalent in the Mediterranean area and in areas where consanguineous marriages are common.
Combined FV and FVIII deficiency can manifest at any age. Epistaxis, easy bruising, post-surgical or post partum bleeding and menorrhagia are the most common symptoms. Hemarthrosis and muscular hematomas may occur. The symptoms are usually mild.
Combined deficiency of factor V and factor VIII is caused by mutations either in the LMAN1 gene (chromosome 18; 18q21) or in the MCFD2 gene (chromosome 2; 2p21). LMAN1 encodes ERGIC-53, a transmembrane lectin, while MCFD2 is an EF-hand-containing protein. The ERGIC-53/MCFD2 protein complex functions as a cargo receptor that facilitates the transport of coagulation factors V and VIII from the endoplasmic reticulum to the Golgi apparatus. Mutations in LMAN1 account for approximately 70% of cases and include only null mutations. Mutations in MCFD2 account for approximately 30% of cases and include both null and missense mutations.
Diagnosis is based on the measurement of factor V and factor VIII levels and on the detection of prolonged activated partial thromboplastin and prothrombin times. Levels of factor V and factor VIII range from as low as 1% to as high as 46%, but generally fall between 5% and 30%.
Differential diagnosis includes co-inheritance of both FV deficiency (chromosome 1) and FVIII deficiency (chromosome X).
Transmission is autosomal recessive.
Management and treatment
Management aims at controlling the bleeding and includes treatments with fresh frozen plasma, FVIII concentrates and desmopressin administration.
The prognosis is favorable for moderate forms of the disease. Management of patients with more severe forms should be carried out at a specialized center.
Article for general public
- Guidance for genetic testing
- Français (2018, pdf)