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Coagulation cascade:. Hereditary coagulation disorders. Haemophilia A: Is most common hereditary disorder of blood coagulation. The inheritance is: sex linked, but 33% of patients have no family history & result from spontaneous mutation. The incidence: 30-100/10 6
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Hereditary coagulation disorders Haemophilia A: Is most common hereditary disorder of blood coagulation. The inheritance is: sex linked, but 33% of patients have no family history & result from spontaneous mutation. The incidence: 30-100/106 The defect is: absence or low level of plasma factor VIII . The gene for factor VIII is located near the tip of the long arm of the X chromosome (Xq2.8), the genetic defects include many deletions & different point mutations.
Clinical features: * Recurrent painful haemarthroses & muscle haematomas dominate the clinical course of severely affected patients with progressive deformity &crippling. *prolonged bleeding occurs after dental extractions. *Haematuria is more common than GIT bleeding. *The clinical severity of the disease is correlate with the extent of coagulation factor deficiency. *Spontaneous intracerebral haemorrhage is an important cause of death in severe disease.
Clinical features: *Haemophilic pseudotumours: may occur in the long bones, pelvis, fingers &toes .These result from repeated subperiosteal haemorrhages with bone destruction, new bone formation, expansion of bone pathological fractures. *many patients have subclinical liver disease & few have clinical features of chronic hepatitis This is largely due to many infusions of blood products & consequence transmission of hepatitis B or C & other non A non B hepatitis & HIV transmission
Factor IX deficiency (Christmas disease, Haemophilia B) The inheritance & clinical features of Factor IX deficiency are identical to those of haemophilia A . The two disorders are distinguished by specific coagulation factor assays. The incidence is 1/5 that of haemophilia A . The factor IX is coded by gene near to that of factor VIII (Xq2.6 region). The factor IX is 1/5 the size of haemophilia A, As in haemophilia A number of mutations & deletions have been found.
Von willenbrand's disease: The incidence: 30-100/106 The inheritance: autosomal dominant with varying expression.
Pathogenesis: The primary defect appears to be reduced synthesis of VWF ,this protein promotes platelet adhesion & is also the carrier molecule for factor VIII ,protecting it from premature destruction & this explain the reduction of factor VIII level in Von willenbrand's disease. The molecular defects that have been identified include: point mutation & major deletions.
Clinical feature: *post operative & post traumatic hemorrhage, mucosal membrane bleeding & excessive blood loss from superficial cuts & abrasions. *haemarthrosis & muscle haematomas are rare except in homozygous cases.
Acquired coagulation disorders: They are more common than the inherited disorders. Unlike the inherited disorders, multiple clotting factor deficiencies are usual. Vitamin K deficiency: Cased by inadequate diet, malabsorption or drugs as warfarin which act as vit.K antagonists is associated with decrease in functional activity of factors : II, VII,IX, X & protein C & S ,but the immunological methods show normal levels of these factors.
