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Inherited Bleeding Disorders Factor X Deficiency Galila Zaher, MRCPath Assistant Professor Consultant Hematologist KAUH
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Stuart-Prower Deficiency. Inherited bleeding disorder. It is due : i. A lower than normal amount of FX ii. or FX which does not work properly. Bleeding when the FX level below 10%
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Incidence Rare factor deficiency. Only 50 cases identified in the world. 1 in 500,000 people. More frequent :consanguinity “Autosomal recessive" disorder. Affects males and females equally No known racial or ethnic predilection.
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Factor Level More than 10% : Few problems 1-10% :Mild to moderate bleeding Less than 1% : Severe bleeding
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Clinical Presentation Age: can present at any age. More severe cases present during infancy Umbilical cord stump bleeding Bleeding after circumcision Hemarthroses Nose bleeds Easy bruising Bleeding in soft tissues and in muscles
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Clinical Presentation Gastrointestinal bleeding Heavy and prolonged menstrual period Hematuria Intracranial bleeding (rare) First-trimester miscarriage &Post-partum bleeding Post surgical traumatic bleeding Petechiae, ecchymoses.
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Replacement Therapy Fresh frozen plasma Prothrombin Complex Concentrate
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Physiology Vitamin K–dependent serine protease First enzyme in the common pathway Inherited or acquired. In 1950s, Telfer reported woman named Prower 1956; Hougie reported man named Stuart 1957. Factor designated Stuart-Prower.
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Clinical Features Heterozygotes : asymptomatic. Homozygous : hemorrhagic symptoms Long arm ch 13, downstream FVII gene It is composed of 8 exons Signal region, a propeptide region, a glutamic acid domain, an ”aromatic stack” region, 2 regions homologous to epidermal growth factor, and a catalytic domain
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Physiology FX Xa (intrinsic & extrinsic clotting cascades). Activation by the :TF-F VIIa. Or by :FIXa and F VIIIa. FXa :Prothrombin thrombin Positive feedback loop by activating FV, VII, and VIII. Inactivating both FVIII and tissue factor. FXa is ultimately inactivated by AT
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Factor X Deficiency Type I deficiency :reduced synthesis Type II deficiency :production of a dysfunctional molecule Complete absence is incompatible with life. Missense mutations
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Several Specific Mutations Gamma-carboxylation Altering cleavage site of factor X Interference with protein folding
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Acquired Deficiency Vitamin K deficiency, Sodium valproate Oral Anticoagulant liver disease Amyloidosis :8% Myeloma Mycoplasma pneumoniae infection,URTI Lupus anticoagulant Leprosy Children with severe burns Topical thrombin administration Leukemia and malignancy intestinal malabsorption
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Lab Studies PT, APTT The Russell viper venom time cleaves FX FXa. Type I : Functional & antigenic are decreased Type II :functional is decreased and antigenic level varies Vitamin K deficiency :other clotting factors reveal decreases
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Treatment Factor X levels 10-40% is usually adequate. Fresh frozen plasma i. Initial dose :15-20 mL/kg ii. Maintenance doses of 3-6 mL/kg q 12-24 hours. PCCs i. Contains F II, VII, IX, and X and protein C. ii. Trace of heparin to guard against thrombosis. iii. Dose calculated depending on concentration of protein C iv. 50-125 U/kg v. No more than 2-3 doses in the first 36-48 h vi. Thrombotic complications
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Acquired, treat underlying cause i. Vitamin K :acquired deficiency ii. Amyloidosis :splenectomy
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Monitor Thrombotic complications i. Administered with rFVIIa, ii. OR antifibrinolytics iii. FX levels >50% Hypersensitivity reaction Clinical response PT, and aPTT should be closely monitored Vit K Adult Dose 10 mg PO/IV/IM/SC Pediatric Dose :1 mg IM as single dose IV :rare anaphylactoid reactions and death
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