Bleeding Disorders in Clinical Hematology

Bleeding Diathesis

• Caused by inherited or acquired defects of vessel wall, platelets number and/or function, and coagulation system
• Characterized by spontaneous bleeding and extensive bleeding after minimal trauma

Vascular Disorders

Congenital

• Ehlers-Danlos syndrome: increased skin elasticity, capillary fragility, and hypermobility of joints
• Hereditary hemorragic telangiectasia: thin and dilated capillary walls, autosomal dominant, presented in adults
• Giant hemangioma: angiomatous malformation

Acquired

• Scurvy (vitamin C deficiency)
• Senile purpura
• Sepsis (meningococcal)
• Steroid-induced
• Malignancy
• Immune (vasculitis)

Clinical Picture

• Purpura (raised)
• Echymosis
• Mucosal bleeding
• Internal bleeding
• Rare muscle bleeding
• Never hemarthrosis
• Positive Hess test and prolonged bleeding time
• Normal CBC, PT, APTT, and clotting time

Henoch-Schonlein Purpura

• Usually seen in children
• Often follows an acute upper respiratory tract infection
• Immunoglobulin A (IgA) - mediated vasculitis
• Characteristic purpuric rash accompanied by localized edema and itching
• Painful joint swelling, hematuria, and abdominal pain may occur
• Usually self-limiting, but occasional patients develop renal failure
• Systemic affection indicates steroid therapy
• Positive Hess test
• Normal platelets, PT, and APTT
• Elevated IgA
• Skin biopsy with IgA deposit

Platelet Disorders

• Disorders of platelet number: thrombocytopenia and thrombocytosis
• Disorders of platelet function

Classification of Platelet Disorders

• Quantitative disorders:
  • Abnormal distribution
  • Dilution effect
  • Decreased production
  • Increased destruction
• Qualitative disorders:
  • Inherited disorders (rare)
  • Acquired disorders
  • Medications
  • Chronic renal failure
  • Cardiopulmonary bypass

Decreased Marrow Production of Megakaryocytes

• Congenital disorders:
  • Thrombocytopenia with absent radii (TAR)
  • Fanconi's anemia (pancytopenia)
• Acquired disorders:
  • Marrow infiltration with malignant cells
  • Marrow fibrosis
  • Aplastic and hypoplastic anemias (idiopathic, drugs, toxins)
  • Deficiency states (vitamin B12, folate)
  • Paroxysmal nocturnal hemoglobinuria

Splenic Sequestration of Circulating Platelets

• Splenic enlargement due to tumor infiltration
• Splenic enlargement due to portal hypertension

Increased Consumption

• DIC
• Hemolytic-uremic syndrome
• Thrombotic thrombocytopenic purpura

Increased Destruction of Circulating Platelets

• Primary:
  • Idiopathic thrombocytopenic purpura (ITP) - acute and chronic
• Secondary:
  • Drug-induced thrombocytopenia
  • Chronic autoimmune disorders (SLE)
  • Infection (HIV, EBV)
  • Malignancies, lymphoma

Idiopathic Thrombocytopenic Purpura (ITP)

• Most common cause of isolated thrombocytopenia
• Autoimmune disease with antiplatelet antibodies and shortened platelet lifespan
• Forms of ITP:
  • Acute ITP:
    • Most common in children
    • Preceded by viral infection
    • Sex equal
    • Spontaneous recovery within 4-6 weeks in 90% of patients
  • Chronic ITP:
    • Typically seen in 20-40-year-olds
    • Women predominant (F:M=3:1)
    • Chronic course
    • Secondary to other autoimmune diseases

Clinical Features of ITP

• Petechiae
• Ecchymoses
• Mucosal membrane bleeding
• Menorrhagia
• Rare internal and intracranial bleeding
• No organomegaly

Diagnosis of ITP

• Platelet count