Inherited Bleeding Disorders Factor X Deficiency

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

Stuart-Prower Deficiency. • 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%

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 • 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 • Vitamin K :acquired deficiency • Amyloidosis :splenectomy

Monitor • 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

Inherited Bleeding Disorders Factor X Deficiency