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Coagulation

Hereditary bleeding disorders

Factor X 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: 16 October 2010, last major update October 2010
Copyright: (c) 2002-2010, PathologyOutlines.com, Inc.

Definition
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● Factor X deficiency is a rare congenital bleeding disorder that is inherited as an autosomal recessive trait, and is characterized by a variable bleeding tendency

Terminology
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● Also known as Stuart-Prower Factor Deficiency
● Deficiency classified as either:
     - Type I: decreased functional activity and antigen level (quantitative defect)
     - Type II: decreased functional activity and near normal antigen level (qualitative defect)

Epidemiology
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● Estimated incidence of 1 in 500,000 to 1,000,000; however, in countries where consanguinity is more common (e.g. Iran), incidence is reported to be 1 in 200,000
● Estimated carrier incidence of 1 in 500

Sites
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● Bleeding into skin and mucosa, joint and muscle, genitourinary tract, gastrointestinal tract, CNS (see clinical features below)

Pathophysiology
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● Factor X is a vitamin K-dependent serine protease produced in the liver
● It is the first enzyme in the common pathway to form a fibrin clot
● Its activated form (in complex with factor Va, Ca++ and phospholipid) cleaves prothrombin to thrombin
● It has a long half-life of 20-40 hours

Coagulation cascade

Etiology
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● Inherited as an autosomal recessive trait
● More than 80 mutations have been identified, which include small deletions, missense and frameshift mutations

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, recurrent fetal loss
● Bleeding symptoms in severe deficiency are similar to that seen in patients with factor VIII (Hemophilia A) and factor IX (Hemophilia B) deficiency
● Heterozygotes are usually asymptomatic but may have mild mucocutaneous bleeds
● Patients with severe deficiency are either homozygous or compound heterozygous
● Bleeding symptoms tend to correlate with factor X activity levels: mild (>6%-10%), moderate (1%-5%) or severe (<1%)
● A small percentage of patients develop factor X inhibitors with factor replacement therapy

Laboratory
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● Prolonged PT and PTT that correct with mixing study
● Prolonged Russell’s viper venom time (measures the direct activation of factor X)
● Normal thrombin and bleeding time
● Factor X specific functional and immunologic assays for confirmation

Prognostic factors
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● Particular genotypes [Gly(-20)Arg, Gly94Arg and Gly380Arg mutations] are associated with higher rates of hemarthrosis and intracranial bleeding

Case reports
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● Factor X deficiency presenting as chronic bilateral subdural hematomas in a 7 month-old infant (Pediatr Neurosurg 2010;46:54)

Treatment
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● For minor bleeding episodes, maintain factor X levels at 10%-15% of normal using FFP (15-20 mL/kg followed by 3-6 mL/kg every 24 hours)
● For major bleeding episodes, trauma or surgical procedures, factor X rich prothrombin complex concentrates can be used to maintain factor X levels at 50% of normal

Differential diagnosis
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● Acquired factor X deficiency (liver disease, vitamin K deficiency): also exhibits reduced levels of other coagulation factors; isolated factor X deficiency is associated with respiratory infection, AML and other malignancies, amyloidosis
● Acquired factor X inhibitors in patients without congenital factor X deficiency are rare but have been reported in leprosy and chemical exposure
● Other factor deficiencies (e.g. factor V, prothrombin)

Additional references
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● Haemophilia 2008;14:1176, Consultative Hemostasis and Thrombosis: Elsevier, 2007

End of Coagulation > Hereditary bleeding disorders > Factor X deficiency

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