Coagulation - Factor V deficiency

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Coagulation

Hereditary bleeding disorders

Factor V deficiency

Reviewers: Kendall Crookston, M.D., Ph.D., University of New Mexico; Lizabeth Rosenbaum, M.D., University of New Mexico; Julie Gober-Wilcox, M.D., Resident, University of New Mexico (see Reviewers page)
Revised: 20 September 2010, last major update August 2010
Copyright: (c) 2002-2010, PathologyOutlines.com, Inc.

Definition / General
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● Factor V deficiency is a rare congenital bleeding disorder that is inherited as an autosomal recessive trait and is characterized by decreased or absent factor V activity

Terminology
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● Also called autoprothrombin I deficiency, Owren’s disease, labile factor deficiency or parahemophilia (severe deficiency)
● Deficiency classified as either:
- Type I: both reduced antigen level and activity (quantitative defect)
- Type II: normal or mildly reduced antigen level and reduced activity (qualitative defect)

Epidemiology
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● Rare, incidence of less than 1 per 1,000,000 in the homozygous form
● Over 200 cases have been described in the literature

Sites
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● Autosomal recessive trait with variable heterozygote expressivity
● There have been 56 mutations described including insertion/deletion, missense, splice site and nonsense mutations (in order of decreasing frequency)
● Parental consanguinity is often present, especially in countries (Muslim or southern India) where consanguineous marriages are common

Pathophysiology
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● Factor V is a plasma glycoprotein that is synthesized in the liver and is also present in platelet a-granules
● Platelet factor V accounts for approximately 20% of the total body pool of factor V
● Factor V is a plasma cofactor for the prothrombinase complex that converts prothrombin to thrombin
● Deficiency leads to predisposition for hemorrhage, while some mutations (most notably factor V Leiden) predispose to thrombosis

Clinical features
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● May be associated with bruising, epistaxis, menorrhagia, GI/GU bleeding, umbilical stump bleeding or bleeding after surgery, trauma, dental procedures, pregnancy or circumcision
● Severe deficiencies may resemble hemophilia A or B, and are associated with intracranial hemorrhage; however hemarthroses are not as common
● There are mild, moderate and severe forms
● Patients with mild to moderate deficiency (>20-30%) have a heterozygous genotype and are usually asymptomatic and may not be diagnosed until adulthood
● Patients with severe deficiency (<10%) have either homozygous or compound heterozygous genotype and typically present within the first 6 months of life
● Levels don’t always correlate with severity of symptoms
● Complications of treatment include the development of factor V alloantibodies (inhibitors)

Laboratory
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● Prolonged PT/PTT with correction after mixing study with normal pooled plasma
● Normal thrombin time
● Specific clot-based factor V assay for diagnosis

Prognostic factors
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● Prognosis is good for most patients with factor V deficiency
● Most severe cases have been in patients who present in the perinatal period with intracranial bleeding

Case reports
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● Severe gestational factor V deficiency presenting with intracranial hemorrhage detected by ultrasound (Haemophilia 2007;13:432)

Treatment
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● Since there are no factor V concentrates available, fresh frozen plasma (FFP) is the mainstay of treatment (15 to 20 mL/kg followed by smaller amounts, such as 5 mL/kg every 12 hours, adjusting the dosage on the basis of Factor V levels, PT and APTT)
● Cryoprecipitate and prothrombin complex concentrates do not contain factor V
● For refractory patients or patients with inhibitors, prothrombin complex concentrates, recombinant activated FVIIa and platelet transfusions have been successfully used
● Patients with inhibitors may need immunosuppression

Differential diagnosis
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● Acquired factor V deficiency (seen in liver disease or patients with DIC)
● Acquired factor V inhibitors
● Combined Factor VIII/Factor V deficiency

Additional references
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● Consultative Hemostasis and Thrombosis (2007), Haemophilia 2008;14:1164, Haemophilia 2009;15:1143, Semin Thromb Hemost 2009; 35:382

End of Coagulation > Hereditary bleeding disorders > Factor V deficiency

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