Inherited Coagulation Disorders Quiz

Inherited Coagulation Disorders

• Coagulation disorders can be inherited or acquired.
• Inherited disorders are rare and often involve a deficiency in only one clotting factor.
• Inherited coagulation disorders result from qualitative or quantitative abnormalities in a coagulation factor.

Coagulation Factor Disorders

• Inherited Bleeding Disorders:
  • Common: Hemophilia A, Hemophilia B, von Willebrand disease
  • Rare: Other factor deficiencies
• Acquired Bleeding Disorders:
  • Liver disease
  • Vitamin K deficiency/warfarin overdose
  • Disseminated Intravascular Coagulation (DIC)

Hemophilia

• Hemophilia is a group of hereditary genetic disorders.
• These disorders impair the body's ability to control blood clotting, which stops bleeding when a blood vessel is broken.

Hemophilia A and B

• Hemophilia A:

  • Factor deficiency: Factor VIII
  • Inheritance: X-linked recessive
  • Incidence: 1/5000 males
  • Severity: Related to factor level; <2% severe, 2-10% moderate, 10-30% mild
  • Complications: Soft tissue bleeding

• Hemophilia B:

  • Factor deficiency: Factor IX
  • Inheritance: X-linked recessive
  • Incidence: 1/20,000-34,000 males
  • Severity: Related to factor level; <2% severe, 2-10% moderate, 10-30% mild
  • Complications: Soft tissue bleeding

Haemophilia A (Classic Haemophilia)

• Sex-linked disorder due to qualitative or quantitative abnormality of factor VIII.
• Hemophilia severity categorized as mild (10-30% normal factor), moderate (2-10% normal factor), and severe (less than 2% normal factor).
• 70% of Haemophilia type A patients have severe form.
• Factor VIII is absent or reduced in Haemophilia A.
• The level of factor vWF is normal.

Haemophilia Inheritance

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

Clinical Features (Hemophilia A)

• Clinical features depend on the level of factor VIII.
• Levels less than 2% are associated with frequent spontaneous bleeding from an early age.
• Hemarthroses (bleeding into joints) are common and can lead to joint deformity.
• Bleeding into muscles is also common; intramuscular injections should be avoided.
• Levels of 2-10% are associated with severe bleeding following injury.
• Levels above 10% produce mild disease, typically only causing bleeding after injury or surgery.
• Diagnosis in this group is often delayed until later in life.

Common Causes of Death (Hemophilia)

• Cerebral hemorrhage
• HIV infection
• Liver disease (due to Hepatitis C)

Laboratory Features (Hemophilia A)

• Bleeding time is normal
• Partial thromboplastin time (PTT) is prolonged
• Prothrombin time (PT) is normal
• Thrombin time (TT) is normal
• Factor VIII levels are reduced
• Von Willebrand Factor (vWF) levels are normal
• Platelet count is normal

Laboratory Features (Hemophilia A) - Further Tests

• Correction (mixing) experiments show Factor VIII deficiency
• Functional Factor VIII assay shows decreased activity
• DNA analysis using PCR or southern blot can be done for diagnosis.
• Treatment: Cryoprecipitate

Complications of Hemophilia Therapy

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

Hemophilia B (Christmas Disease)

• Sex-linked disorder (similar to Hemophilia A) due to qualitative or quantitative abnormalities of factor IX.

Laboratory Features (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.

Further Laboratory Features/Treatment (Hemophilia B)

- Correction (mixing) tests show Factor IX deficiency
-  Functional Factor IX shows decreased activity
- DNA analysis using PCR or southern blot can be done.
- Treatment: High-purity Factor IX or Recombinant human Factor IX

Haemophilia C (Jews)

• Mild form of haemophilia, affecting both sexes.
• Fourth most common coagulation disorder after von Willebrand's disease and haemophilia A and B.
• Thought to affect 1 in 100,000 adults.

Additional Information (Haemophilia C)

• Caused by factor XI deficiency.
• Distinguished from haemophilia A and B as it doesn't lead to joint bleeding.
• Autosomal inheritance.
• Patients with absent factor XI may develop inhibitors to factor XI.

Clinical features (Haemophilia C)

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

Test your knowledge on inherited coagulation disorders and their impact on blood clotting. This quiz covers various bleeding disorders including Hemophilia A and B, as well as the factors involved. Challenges will include both common and rare conditions, along with their characteristics and inheritance patterns.