Inherited Bleeding Disorders Factor X Deficiency Galila Zaher, MRCPath Assistant Professor Consultant Hematologist KAUH

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%

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 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 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 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 U/kg v. No more than 2-3 doses in the first h vi. Thrombotic complications

Acquired, treat underlying cause i. Vitamin K :acquired deficiency ii. Amyloidosis :splenectomy

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