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Inherited Bleeding Disorders Factor X Deficiency Galila Zaher, MRCPath Assistant Professor Consultant Hematologist KAUH Stuart-Prower Deficiency. ii. Inherited bleeding disorder. It is due : A lower than normal amount of FX or FX which does not work properly. Bleeding when the FX level below 10% i. 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. Factor Level More than 10% : Few problems 1-10% :Mild to moderate bleeding Less than 1% : Severe bleeding 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 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. Replacement Therapy Fresh frozen plasma Prothrombin Complex Concentrate 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 . 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 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 Factor X Deficiency Type I deficiency :reduced synthesis Type II deficiency :production of a dysfunctional molecule Complete absence is incompatible with life. Missense mutations Several Specific Mutations Gamma-carboxylation Altering cleavage site of factor X Interference with protein folding 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 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 Treatment i. ii. i. ii. iii. iv. v. vi. Factor X levels 10-40% is usually adequate. Fresh frozen plasma Initial dose :15-20 mL/kg Maintenance doses of 3-6 mL/kg q 12-24 hours. PCCs Contains F II, VII, IX, and X and protein C. Trace of heparin to guard against thrombosis. Dose calculated depending on concentration of protein C 50-125 U/kg No more than 2-3 doses in the first 36-48 h Thrombotic complications Acquired , treat underlying cause i. Vitamin K :acquired deficiency ii. Amyloidosis :splenectomy Monitor i. ii. iii. Thrombotic complications Administered with rFVIIa, OR antifibrinolytics 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