أسئلة الثالثة هيماتولوجي ثالثة الدلتا

Hemolytic Anemias

• These anemias result from a shortened survival of circulating red blood cells (RBCs) due to premature destruction
• A typical RBC lifespan is normally 120 days (4 months), during which time RBCs are subject to mechanical stress
• Hemolysis occurs when an RBC can no longer maintain its intact structure

Classification

• Hemolytic anemias are classified according to the site of hemolysis and etiology

Sites of Hemolysis

• Can occur extravascularly or intravascularly
• Extravascular hemolysis involves the breakdown of RBCs by macrophages of the reticuloendothelial system, primarily in the marrow, liver, and spleen
  • This the primary means of normal red cell destruction
• Intravascular hemolysis involves the breakdown of red cells within blood vessels
  • Normal red cell destruction has little or no part in this

Etiology of Hemolysis

• Can be hereditary or acquired
• Hereditary causes:
  • RBC membrane defects, such as hereditary spherocytosis and elliptocytosis
  • RBC metabolic defects, like G6PD and pyruvate kinase deficiency
  • Hemoglobin defects, involving genetic abnormalities (e.g., Hb S, Hb C, unstable Hb, thalassemia)
• Acquired causes:
  • Immune-related issues like autoimmune (Warm AIHA and Cold AIHA) and alloimmune reactions (hemolytic transfusion reactions and hemolytic disease of the newborn)
  • Drug-associated hemolysis
  • Red cell fragmentation syndromes
  • March hemoglobinuria
  • Infections like malaria
  • Chemical and physical agents (drugs, burns)
  • Secondary liver and renal disease
  • Paroxysmal nocturnal hemoglobinuria

General Laboratory Findings

• Increased serum bilirubin, mostly unconjugated or indirect
• Increased urine urinobilinogen
• Increased stool stercobilinogen
• Elevated serum LDH
• Absent serum haptoglobins
• Reticulocytosis is present
• Bone marrow hyperplasia will be observed
• Blood film may show abnormal RBC morphology
• Specific tests can help identify the cause of hemolysis
• Findings specific to intravascular hemolysis include hemoglobinaemia, hemoglobinuria, hemosidinuria, and methemalbuminemia

Autoimmune Hemolytic Anemia (AIHA)

• AIHA is caused by autoantibodies directed against erythrocyte self-antigens
• It is a heterogenous condition, ranging from fully compensated to life-threatening
• Pathogenesis involves autoantibodies, mainly directed against RBC, with or without complement activation, dominating the clinical picture

Types of AIHA

• Warm Type:
  • IgG autoantibodies with complement are usually present
  • The optimal temperature is at 37°C
  • Can be idiopathic, secondary to immune diseases (SLE), malignancy (CLL, lymphoma), or drugs (methyldopa)
• Cold Type:
  • IgM autoantibodies with complement are usually present
  • Optimal temperature is at lower than 37°C
  • Can be idiopathic, secondary, due to infection (IMN), or related to malignancy (lymphoma)

Clinical Manifestations

• Onset of anemia may be rapid or insidious
• Signs of anemia may be apparent (uncompensated hemolysis)
• General symptoms of hemolysis such as jaundice
• Hemolytic crises can occur
• Mild splenomegaly may develop
• Other clinical signs related to the underlying etiology

Investigations

• General lab features of hemolysis should point to the presence of an issue
• Blood film may reveal RBC agglutination and spherocytes
• Direct Coombs test will yield strong positive results
• Further investigations may be required to exclude secondary causes

Differential Diagnosis

• Must exclude and differentiate from hereditary spherocytosis, and drug-induced hemolytic anemia

Treatment

• Treatment of warm AIHA:
  • Treat the underlying cause if known
  • First-line treatment is corticosteroids, which are effective in about 50% of cases
  • Second-line options include splenectomy, monoclonal antibodies (Anti-CD20/rituximab), and immunosuppression (azathioprine, cyclophosphamide, and cyclosporin A)
  • Folic acid may be given to severe cases
  • Blood transfusion may be needed if anemia is severe and causing symptoms
• Treatment of cold AIHA:
  • Avoid exposure to cold
  • If transfusion is necessary, use a blood warmer
  • Treat the underlying cause
  • Monoclonal antibodies (Anti-CD20/rituximab)
  • Corticosteroids and splenectomy are generally ineffective
  • Complement pathway inhibitors