Inherited Coagulation Disorders Quiz

Inherited Coagulation Disorders

• Coagulation disorders can be inherited or acquired.
• Inherited disorders are rare and often involve a deficiency in a single clotting factor.
• Inherited coagulation disorders stem from abnormalities in the quality or quantity of a clotting factor.

Coagulation Factor Disorders

• Inherited bleeding disorders
  • Common: Hemophilia A, Hemophilia B, von Willebrand's disease
  • Rare: Deficiencies in other clotting factors
• Acquired bleeding disorders
  • Common causes: Liver disease, Vitamin K deficiency, Warfarin overdose, Disseminated Intravascular Coagulation (DIC)

Hemophilia

• A group of hereditary genetic disorders.
• Impairs the body's ability to control blood clotting.
• Used to stop bleeding after a blood vessel breaks.

Hemophilia A and B

• Hemophilia A:
  • Factor VIII deficiency
  • X-linked recessive inheritance
  • Incidence: 1 in 5000 males
  • Severity varies based on factor level
    • <2%: Severe (spontaneous bleeding)
    • 2-10%: Moderate (bleeding with mild injury)
    • 10-30%: Mild (bleeding with surgery or trauma)
  • Complications: Soft tissue bleeding
• Hemophilia B:
  • Factor IX deficiency
  • X-linked recessive inheritance
  • Incidence: 1 in 20,000-34,000 males
  • Severity varies based on factor level
    • <2%: Severe (spontaneous bleeding)
    • 2-10%: Moderate (bleeding with mild injury)
    • 10-30%: Mild (bleeding with surgery or trauma)
  • Complications: Soft tissue bleeding

Haemophilia A (Classic Haemophilia)

• Sex-linked disorder, caused by qualitative or quantitative abnormality of factor VIII.
• Severity categorized by factor VIII levels:
  • Mild: 10-30% normal factor
  • Moderate: 2-10% normal factor
  • Severe: Less than 2% normal factor
• 70% of hemophiliacs with type A have the severe form.
• In Haemophilia A, factor VIII is absent or reduced; Factor vWF is normal.

Inheritance of Haemophilia

• If a female carrier has a son, there is a 50% chance he will have hemophilia, and a 50% chance that her daughter will be a carrier.
• All daughters of men with hemophilia are carriers, and the sons are normal

Clinical Features of Hemophilia A

• Clinical features depend on the level of factor VIII.
• Less than 2% factor VIII levels are associated with frequent spontaneous bleeding from early life.
• Haemarthroses (bleeding into joints) are common and can lead to joint deformity.
• Bleeding into muscles is common; intramuscular injections should be avoided.

Clinical Features of Hemophilia A (additional info)

• Levels of 2-10% are associated with severe bleeding following injury.
• Levels above 10% usually lead to mild disease, with bleeding only after injury or surgery.
• Diagnosis in this group is often delayed until later in life.

Common Causes of Death in Hemophilia

• Cerebral haemorrhage
• HIV infection (due to hepatitis C)

Laboratory Features of Hemophilia

• Bleeding time is normal
• Partial thromboplastin time (PTT) is prolonged
• Prothrombin time (PT) is normal
• Thrombin time (TT) is normal
• vWF level is normal
• Platelet count is normal
• Abnormal findings: prolonged APTT and reduced factor VIII level.

Laboratory Features of Haemophilia A and Additional Tests

• Correction (mixing) experiments show factor VIII deficiency.
• Functional factor VIII assay shows decreased activity.
• DNA analysis (PCR or Southern blot) can be done.
• Treatment of hemophilia A: Cryoprecipitate.

Complications of Therapy

• Formation of inhibitors (antibodies): 10-15% of severe hemophilia A patients, 1-2% of severe hemophilia B patients.
• Viral infections: Hepatitis B, Hepatitis C, HIV, parvovirus, Hepatitis A (Other)

Hemophilia B (Christmas Disease)

• Sex-linked disorder (like hemophilia A).
• Caused by qualitative or quantitative abnormality of factor IX

Laboratory Features of Hemophilia B

• Bleeding time is normal
• PTT is prolonged
• PT is normal
• TT is normal
• Platelet count is normal
• Factor VIII assay shows normal activity
• Factor IX assay shows decreased activity

Laboratory Features of Hemophilia B (cont'd)

• Correction (mixing) experiments show factor IX deficiency.
• Functional factor IX assay shows decreased activity.
• DNA analysis (PCR or Southern blot) can be done.
• Treatment of hemophilia B: High purity factor IX, Recombinant human factor IX.

Haemophilia C (Jews)

• A mild form of hemophilia affecting both sexes.
• The fourth most common coagulation disorder after von Willebrand's disease and hemophilia A and B.
• Thought to affect 1 in 100,000 of the adult population.

Haemophilia C (additional info)

• Caused by a deficiency of coagulation factor XI.
• Distinguished from hemophilia A and B as it does not lead to bleeding into joints.
• Autosomal inheritance.
• Patients with absent factor XI may develop inhibitors to factor XI.

Clinical Features of Haemophilia C

• Prolonged bleeding from injuries
• Frequent or heavy nosebleeds
• Traces of blood in the urine
• Heavy menstrual bleeding in females

Test your knowledge on inherited coagulation disorders, including hemophilia and other bleeding disorders. This quiz covers important factors such as their causes, types, and genetic implications. Understand the distinctions between inherited and acquired coagulation issues.