Factor 13 Deficiency

1. Factor 13 Deficiency Presented By MUHAMMAD SULEMAN RAZA CHANGAIZ DIL ESSA

2. ● Factor XIII deficiency is a congenital disorder that is inherited as an autosomal recessive trait and is associated with a variable bleeding tendency ● Acquired factor XIII deficiency is associated with liver failure, inflammatory bowel disease, leukemia, disseminated intravascular coagulation, Henoch-Schonlein purpura, systemic lupus erythematosus and exposure to certain drugs (phenytoin, isoniazid, valproate)

3. Terminology ● Factor XIII is also known as fibrin stabilizing factor

4. Epidemiology ● Estimated at 1 in 2 to 5 million births● More frequent in regions where consanguineous marriages are more common

5. Sites ● Skin and mucosa, joints, soft tissue, gastrointestinal tract, genitourinary tract, CNS

6. Pathophysiology ● Factor XIII is a transglutaminase that circulates as a zymogen comprised of 2 catalytic A subunits and 2 carrier B subunits● The A subunit is synthesized in platelets, monocytes and macrophages while the B subunit is synthesized in the liver; the A and B dimers then assemble in the plasma to form a heterotetramer● Factor XIII is activated by thrombin and is responsible for catalyzing the final step in the coagulation cascade by cross-linking fibrin (in the presence of calcium)● Deficiency is due to a defect in either the A gene (type 2) or B gene (type 1)

8. Etiology ● Inherited as an autosomal recessive trait● Most cases are due to mutations in A subunit gene on chromosome 6● More than 70 mutations have been identified, most of which are missense and nonsense mutations● Only 5 mutations in FXIII B deficient patients have been identified; gene is on chromosome 1

9. Clinical features ● Variable bleeding tendency, from mild to severe depending on factor levels● Umbilical cord stump bleeding, intracranial hemorrhage, soft tissue hematoma, bleeding after circumcision, gastrointestinal bleeding, gingival bleeding, epistaxis, hematuria, surgical site bleeding, menorrhagia, joint bleeding, delayed healing, spontaneous abortion, recurrent miscarriage● Plasma half –life is 9-12 days● Factor XIII levels above 3-5% are usually sufficient to prevent spontaneous bleeding● Severe bleeding typically occurs in individuals with <1% circulating levels● Compound heterozygotes are usually asymptomatic

10. Laboratory● Normal PT, PTT, thrombin time, fibrinogen● Screening test for factor XIII deficiency uses the clot solubility test in which patient plasma is incubated with thrombin and calcium; deficiency will cause the clot to dissolve in the presence of urea or acid● A standard mixing test using patient plasma and normal pooled plasma is usually performed to rule out the presence of an inhibitor● Confirmatory testing uses a quantitative factor XIII activity assay

11. Prognostic factors ● Although there is a life-long risk of bleeding, prognosis is excellent due to good response to treatment; subsequent risk of development of inhibitors is low

12. Case reports ● Spontaneous splenic rupture in a patient with factor XIII deficiency

13. Treatment ● Factor XIII concentrate, FFP or cryoprecipitate for replacement therapy or for treatment of acute bleeding episodes:● Factor XIII concentrate: 10-20U/kg at 4-6 week intervals● FFP: 10 mL/kg every 4-6 weeks● Cryoprecipitate: 1 bag per 10-20 kg every 3-4 weeks● To prevent miscarriage, maintain factor XIII levels >10% in early gestation and >30% at time of delivery to prevent significant bleeds

14. reference • http://www.pathologyoutlines.com/topic/coagulationfactorXIIIdef.html