Patho

• Haemophilia


  Inherited disorder involving intrinsic coagulation pathway
• Subtypes of Haemophilia


  • Haemophilia A (Most common)
  • Haemophilia B
  • Haemophilia C (Rare)
• Haemophilia A


  Inherited (X-linked recessive disorder) factor VIII deficiency
• Haemophilia B


  Inherited (X-linked recessive disorder) factor IX deficiency
• Haemophilia C


  Rare autosomal recessive disorder; due to inherited factor XI deficiency
• When we talk about Haemophilia in an unspecified manner, we think about Haemophilia A
• Haemophilia A


  Occurs due to inherited deficiency of Factor VIII
• Pathogenesis of Haemophilia A

  1. Factor VIII gene is situated near the tip of the long arm of the X chromosome

  2. The protein is synthesized in endothelial cells

  3. The defect in Haemophilia-A is an absence or low level of plasma factor VIII
• Haemophilia A is a common hereditary clotting factor deficiency with a prevalence of 30–100 per million population
• Haemophilia is a disorder of intrinsic coagulation pathway
• Males are usually affected in Haemophilia A
• Clinical presentation of Haemophilia A

  • Tendency toward easy bruising and hemorrhage after trauma or operative procedures
  • Spontaneous hemorrhages in tissues subject to mechanical stress, particularly the joints, leading to recurrent bleeds (hemarthroses) and progressive deformities
  • Petechiae are characteristically absent

  
• Clinical presentation of severe Haemophilia

  • Recurrent spontaneous haemarthrosis and soft tissue haemorrhage from around 6 months onwards
  • Long-term morbidity relates primarily to the development of haemophilic arthropathy with pain and deformity and the need for arthroplasty at a young age

  
• Muscle hematoma in hemophiliacs

  • Bleeding into muscles includes 10 to 25 % of hemorrhagic episodes in severe hemophilia and hematoma formation is common
  • Leg muscles (eg, quadriceps, iliopsoas) are often affected

  
• Intracranial hemorrhage (ICH) in Haemophiliacs

  • Relatively rare compared with other sites of bleeding, but one of the most serious events resulting in high rates of mortality and disability
  • Percentage of ICH causing death has declined from 75% to about 30% due to earlier diagnosis and greater use of prophylactic factor administration
• Transfusion transmitted infection related complications in Haemophiliacs

  • In the 1980s and early 1990s, clotting factor products caused the transmission of Hepatitis B, Hepatitis C and HIV, resulting in high deaths
  • Such cases have decreased significantly nowadays
• Laboratory Diagnosis of Haemophilia A

  1. Activated partial thromboplastin time (PTT) is prolonged

  2. Factor VIII clotting assay shows decreased level of Factor VIII

  3. Prothrombin time (PT) is normal

  4. Platelet count is normal

  
• Haemophilia-B


  1. linked disorder caused by mutations in coagulation factor IX, clinically identical to hemophilia A
• Haemophilia A and B are identical clinically and pathologically, differing only in the deficient factor
• Laboratory Diagnosis of Haemophilia-B

  1. aPTT/PTT is prolonged and the PT is normal

  2. Diagnosis is possible only by assay of the factor IX levels

  3. The disease is treated with infusions of recombinant factor IX