Concise Notes on Hemolytic Anemia

Hemolytic Anemia Overview

  • Premature destruction of red blood cells (RBCs), reducing their survival rate.
  • Categorized as intrinsic/extrinsic and intravascular/extravascular.

Hemolytic Process & Bilirubin Metabolism

  • Hemoglobin released, broken down into heme, then unconjugated bilirubin.
  • Unconjugated bilirubin is processed in the liver to become water-soluble.

Key Terms

  • Hemolysis: Destruction of RBCs.
  • Hemoglobin (Hgb/Hb): Oxygen-carrying protein in RBCs.
  • Lactate Dehydrogenase (LDH): Enzyme released upon cell damage.
  • Heme: Iron-containing component of hemoglobin.
  • Unconjugated Bilirubin (Indirect): Not water-soluble; increases in hemolysis.
  • Conjugated Bilirubin (Direct): Water-soluble; part of bile.
  • Urobilinogen: Formed from conjugated bilirubin by bacteria in the colon.
  • Stercobilin: Excreted in feces.
  • Urobilin: Excreted in urine.
  • Jaundice/Icterus: Yellowing of skin/eyes due to high bilirubin.
  • Unconjugated Hyperbilirubinemia: Indicates pre-liver hemolysis.
  • Conjugated Hyperbilirubinemia: Indicates liver dysfunction or obstruction.

Lab Results in Hemolysis

  • Decreased Hgb/Hb, increased indirect bilirubin, increased LDH, increased reticulocyte count.

Clinical Pathology of Hemolysis

  • Liver function tests (AST/ALT) are typically normal or mildly elevated.
  • ↓ Hgb/Hb
  • ↑ Indirect Bili
  • ↑ LDH
  • ↑ Reticulocyte Count
  • AST/ALT: usually normal or mildly increased.

Intrinsic vs. Extrinsic Hemolytic Anemia

  • Intrinsic: Inherited defects within RBCs (e.g., hemoglobinopathies).
  • Extrinsic: External factors (e.g., immune-mediated, infection).

Intravascular vs. Extravascular Hemolysis

  • Intravascular: Occurs within blood vessels.
    • Causes: Complement-related, microangiopathic, mechanical destruction, chemical/thermal damage.
    • Lab findings: ↓ hemoglobin, ↑ retic, ↑↑ LDH, ↑ indirect bilirubin, ↓ haptoglobin, schistocytes.
  • Extravascular: Occurs primarily in the spleen.
    • Causes: Hemoglobinopathies, membrane abnormalities, enzyme deficiencies, immune-mediated.
    • Lab findings: ↓ hemoglobin, ↑ retic, ↑ LDH, ↑ indirect bilirubin, normal haptoglobin, spherocytes; jaundice/icterus; splenomegaly.

Hemolytic Disease of the Newborn (HDN)

  • Maternal IgG antibodies against fetal RBCs causing destruction.
  • Rh incompatibility is most common (Rhesus/antigen D).
  • Severity increases with successive pregnancies.
  • Prevention: Rho(D) immune globulin (RhoGAM) at 26-28 weeks and after delivery of Rh+ baby.
  • Treatment:
    • Severe anemia (hematocrit < 25%) and/or severe hyperbilirubinemia: exchange transfusion preferred.
    • Moderate anemia (hematocrit 25-35%) and non-severe hyperbilirubinemia: simple pRBC transfusion.
    • Mild anemia (hematocrit > 35%) and non-severe hyperbilirubinemia: no transfusion, treat as neonatal unconjugated hyperbilirubinemia.

Membranopathies: Hereditary Spherocytosis (HS) and Hereditary Elliptocytosis (HE)

  • Inherited disorders affecting RBC membrane, leading to abnormal shapes and premature destruction.
  • Hereditary Spherocytosis (HS):
    • Autosomal dominant, deficiency of cytoskeletal support proteins leading to spheroid shape.
    • Labs: (+) Osmotic fragility test/EMA binding test, RBC band 3 protein reduction, ↑↑ Retic, ↑ bilirubin (indirect), ↑ MCHC, DAT (-), Spherocytes (small, dense, lacking central pallor), Howell-Jolly bodies.
    • Treatment: Supportive care, splenectomy.
    • Beware of Parvovirus B19.
  • Hereditary Elliptocytosis (HE):
    • Autosomal Dominant
    • Homozygous patients with chronic hemolysis generally have moderate to severe anemia (Hb 9-12 g/dl) with elevated retic
    • Blood smear: Elliptocytes (ovalocytes), poikilocytes and microspherocytes if severe.

Hereditary Pyropoikilocytosis (HPP)

  • Peripheral Blood Smear Findings: Marked anisocytosis with numerous rod-shaped elliptocytes and bizarre red cell forms.
  • Anemia: Typically microcytic, hypochromic anemia.

Enzymopathies: G6PD Deficiency and Pyruvate Kinase (PK) Deficiency

  • Inherited enzyme deficiencies affecting RBC metabolism.
  • G6PD Deficiency:
    • X-linked recessive; triggers include oxidative drugs, infection, fava beans.
    • Labs: DAT (-), ↑ LDH while actively hemolyzing, G6PD quantification; blood smear shows bite cells, blister cells, Heinz bodies.
    • Treatment: Supportive care, avoid triggers.
    • Contraindicated Drugs: Dapsone, Nitrofurantoin, Methylene blue, Pegloticase, Phenazopyridine, Primaquine, Rasburicase, Tafenoquine.
  • Pyruvate Kinase (PK) Deficiency:
    • Autosomal recessive; variable presentation.
    • Labs: Anemia (varies), ↑ indirect bilirubin, ↑ retic, normal osmotic fragility, ↓ erythrocytic PK enzymatic activity.
    • Treatment: Supportive care, partial splenectomy.

Autoimmune Hemolytic Anemia (AIHA)

  • Autoantibodies against RBC surface antigens.
  • Primary (idiopathic) or secondary to other conditions.
  • Laboratory Testing:
    • Direct Coombs Test (Direct Antiglobulin Test [DAT]): (+) in AIHA.
    • Detects IgG and C3 (complement) on antibody-coated RBCs.
    • Warm Ab (IgG): Coombs (+) IgG and C3.
    • Cold Ab (IgM): Coombs (+) C3 only.
      • Note: Indirect Coombs detects antibodies against RBCs in serum.

Differential Diagnosis Considerations

  • Consider rare conditions like systemic loxoscelism.
  • Systemic Loxoscelism:
    • Can result in DAT+ hemolytic anemia with reactive leukocytosis and thrombocytosis.