Hemolytic Anemias

HA Overview & Types - Red Cell Rundown

• Hemolytic Anemia (HA): Premature RBC destruction (lifespan < 100-120 days); anemia if marrow compensation fails.
• Key Markers: Reticulocytosis, ↑LDH, ↑Indirect Bilirubin, ↓Haptoglobin (more in IVH).
• Classification:
  • Site:
    • Intravascular (IVH): In circulation; severe; schistocytes.
    • Extravascular (EVH): In spleen/liver; common; spherocytes.
  • Cause:
    • Intrinsic: Defect within RBC (e.g., membrane, enzyme, Hb).
    • Extrinsic: External factor damaging RBC (e.g., immune, mechanical).

⭐ Extravascular hemolysis (e.g., in spleen, liver) is more common and generally less severe than intravascular hemolysis.

HA Diagnosis - Spotting the Signs

• Clinical Clues: Pallor, jaundice (icterus), splenomegaly, dark urine (hemoglobinuria).
• Initial Labs (The "Hemolysis Panel"):
  • CBC: ↓Hb, ↓Hct.
  • Peripheral Smear: Key for morphology (e.g., spherocytes, schistocytes).
  • Reticulocyte Count: ↑ (Reticulocyte Production Index, RPI > 2-3).
  • LDH: ↑ (marker of cell breakdown).
  • Indirect Bilirubin: ↑.
  • Haptoglobin: ↓ (binds free Hb).
  • Urine: Hemoglobinuria, hemosiderinuria.
• Specific Tests:
  • Direct Antiglobulin Test (DAT/Coombs): Positive in AIHA.

⭐ A reticulocyte count corrected for anemia (Reticulocyte Production Index, RPI > 2-3) is the hallmark of hemolytic anemias, indicating appropriate bone marrow response.

Inherited HA - Born This Way

• RBC Membrane Defects: Structural abnormalities leading to premature RBC destruction.
  • Hereditary Spherocytosis (HS): Most common inherited HA in Northern Europeans. Autosomal Dominant (AD) typically (75%). Defects in ankyrin, spectrin, band 3, or protein 4.2.
    • Clinical Triad: Anemia, jaundice, splenomegaly. Gallstones common. Aplastic crisis (Parvovirus B19).
    • Labs: Spherocytes (↓MCV, ↑MCHC), reticulocytosis. Osmotic fragility test (+), EMA binding test (flow cytometry) is diagnostic.
    • Rx: Folic acid. Splenectomy for moderate/severe cases (usually after age 5-6 years) cures hemolysis but spherocytes persist.
  • Hereditary Elliptocytosis (HE) & Pyropoikilocytosis (HPP): Spectrin defects. HE often asymptomatic or mild; HPP is severe.
• RBC Enzyme Defects: Impaired RBC metabolism.
  • G6PD Deficiency: X-linked recessive. Most common enzyme defect. ↓G6PD → ↓NADPH → oxidative stress vulnerability.

    ⭐ In G6PD deficiency, acute hemolysis is typically triggered by oxidative stress (e.g., drugs like primaquine, infections, fava beans), leading to Heinz body formation.

    • Labs: Heinz bodies (denatured Hb, visible with crystal violet/supravital stain), bite cells. G6PD enzyme assay (NB: perform weeks after acute episode as young RBCs have higher G6PD).
  • Pyruvate Kinase (PK) Deficiency: Autosomal Recessive (AR). ↓ATP → rigid RBCs → extravascular hemolysis. Second most common enzyme defect.
    • Clinical: Neonatal jaundice, chronic hemolysis, splenomegaly. No specific crisis triggers like G6PD.
    • Labs: Echinocytes (burr cells). PK enzyme assay.

Acquired HA - Attack from Outside

• Immune-Mediated:
  • Autoimmune (AIHA):
    • Warm AIHA (IgG, extravascular hemolysis; DAT: IgG ± C3)
    • Cold Agglutinin Disease (IgM, complement, intravascular hemolysis; DAT: C3)
    • Paroxysmal Cold Hemoglobinuria (PCH; Donath-Landsteiner Ab, IgG)
  • Alloimmune: Hemolytic Disease of Fetus & Newborn (HDFN; maternal IgG), Transfusion reactions.
• Non-Immune Mediated:
  • Microangiopathic Hemolytic Anemia (MAHA): TTP, HUS, DIC; Schistocytes.
  • Infections: Malaria, Clostridia, Babesia.
  • Drugs/Toxins: e.g., Penicillin (immune), Dapsone (oxidative), Lead.
  • Mechanical Trauma: Prosthetic valves, March hemoglobinuria.
  • Paroxysmal Nocturnal Hemoglobinuria (PNH): Acquired GPI-anchor defect (↓CD55/CD59); intravascular hemolysis, thrombosis.
  • Hypersplenism.

⭐ Warm AIHA is typically IgG-mediated and extravascular, while Cold Agglutinin Disease is IgM-mediated and can cause intravascular hemolysis upon cold exposure.

High‑Yield Points - ⚡ Biggest Takeaways

• Hereditary Spherocytosis: AD, spectrin defect; ↑ MCHC, positive osmotic fragility test.
• G6PD Deficiency: X-linked, episodic hemolysis from oxidant stress (drugs, fava); Heinz bodies, bite cells.
• Sickle Cell Anemia: HbS (Glu→Val); vaso-occlusion, autosplenectomy, Parvovirus B19 aplastic crisis.
• Beta-Thalassemia Major: Severe anemia, hepatosplenomegaly, "chipmunk facies" (extramedullary hematopoiesis), transfusion-dependent.
• AIHA: Warm (IgG) vs Cold (IgM); Direct Coombs Test is key diagnostic.
• PNH: Acquired PIGA mutation, CD55/CD59 deficiency; causes intravascular hemolysis, thrombosis.