Hemolytic Anemias

Intro & Classification - Red Cell Wreckage

Hemolytic Anemia (HA) involves premature destruction of Red Blood Cells (RBCs), reducing their lifespan from the normal 120 days. This "wreckage" occurs either:

• Intravascularly: Directly within blood vessels.
• Extravascularly: Via phagocytosis in the Reticuloendothelial System (RES), mainly spleen and liver.

Key Distinctions: Intravascular vs. Extravascular Hemolysis

⭐ A hallmark of intravascular hemolysis is a significant drop in serum haptoglobin, binding free hemoglobin from lysed RBCs.

Membrane Defects - Shape Shifters

• Hereditary Spherocytosis (HS)
  • Primarily autosomal dominant; defects in RBC membrane proteins (Ankyrin, Spectrin).
  • Results in loss of membrane surface area → spherocytes (rigid, easily destroyed in spleen).
  • Key lab findings: ↑MCHC (often >36 g/dL), ↑RDW, positive osmotic fragility test.
  • 📌 HS Management: Splenectomy (severe cases), Supplements (folic acid), Supportive care.

  • ⭐ Aplastic crisis (often due to Parvovirus B19 infection) is a known complication.

• Hereditary Elliptocytosis (HE)
  • Similar defects (e.g., Spectrin, Protein 4.1); RBCs are elliptical.
  • Most individuals are asymptomatic or exhibit mild, compensated hemolysis.

Enzyme Deficiencies - Energy Crisis

• G6PD Deficiency: X-linked. ↓G6PD $\rightarrow$ ↓NADPH $\rightarrow$ oxidative stress.
  • Heinz bodies, Bite cells (splenic removal).
  • Triggers: 📌 Fava beans, Infections, Drugs (Sulfonamides, Primaquine, Nitrofurantoin, Dapsone - "Spleen Purges Nasty Deposits").
• Pyruvate Kinase (PK) Deficiency: Autosomal recessive (AR). ↓PK $\rightarrow$ ↓ATP $\rightarrow$ RBC membrane instability, chronic hemolysis.
  • Rigid RBCs, extravascular hemolysis.

  ⭐ G6PD deficiency is the most common human enzyme defect; confers malaria protection.

Hemoglobinopathies (Hemolytic) - Globin Grief

• Sickle Cell Anemia (SCA): HbS (Glu→Val at β-globin position 6).
  • Features: Vaso-occlusion (pain), hemolytic crisis, aplastic crisis (Parvovirus B19), autosplenectomy (↑risk encapsulated bacteria).
  • Smear: Sickle cells, Howell-Jolly bodies.
• Unstable Hemoglobins:
  • Precipitate as Heinz bodies → RBC membrane damage → hemolysis.
  • E.g., Hb Köln.

⭐ Autosplenectomy in SCA increases susceptibility to encapsulated organisms like S. pneumoniae.

Immune Hemolysis - Friendly Fire

Antibodies target self RBCs causing destruction.

• Autoimmune Hemolytic Anemia (AIHA):
  • Warm: IgG. 📌 Warm weather is Great (IgG).
  • Cold: IgM (Mycoplasma/Mono). 📌 Cold weather is Miserable (IgM).
  • PCH: Donath-Landsteiner Ab (IgG), biphasic.
• Drug-Induced (DIIHA):
  • Types: Hapten (e.g., Penicillin), Immune complex (e.g., Quinidine), Autoantibody (e.g., Methyldopa).
• Tests: Coombs (DAT on RBCs; IAT in serum).

⭐ Warm AIHA DAT: IgG ± C3d. Cold AIHA DAT: C3d only (IgM elutes).

Non-Immune Acquired Hemolysis - Red Cell Trauma

• Microangiopathic Hemolytic Anemia (MAHA): RBC fragmentation.
  • Schistocytes (helmet cells) on peripheral smear.
  • Causes: TTP (ADAMTS13 activity <10%), HUS, DIC.
• Paroxysmal Nocturnal Hemoglobinuria (PNH):
  • Acquired defect in GPI anchor synthesis → deficiency of CD55 (DAF) & CD59 (MIRL).
  • 📌 PNH: Gotta Pee Inky (hemoglobinuria), GlycosylPhosphatidylInositol anchor defect.
  • Tests: Ham test (acidified serum lysis), flow cytometry for CD55/CD59 (gold standard).

  ⭐ PNH is associated with an increased risk of venous thrombosis, especially in unusual sites (e.g., hepatic, portal, cerebral veins).

• Infections:
  • Malaria (esp. P. falciparum - blackwater fever).
  • Clostridium perfringens sepsis (lecithinase).
• Other Causes:
  • Severe burns.
  • Toxins (e.g., copper, lead, snake venom).
  • Mechanical heart valves (older types).

High‑Yield Points - ⚡ Biggest Takeaways

• Core indicators: ↑Reticulocytes, ↑LDH, ↑Indirect Bilirubin, ↓Haptoglobin signify RBC lysis.
• Intravascular hemolysis: Hemoglobinemia, hemoglobinuria, hemosiderinuria (e.g., PNH, MAHA).
• Extravascular hemolysis: Splenomegaly, spherocytes often seen (e.g., Hereditary Spherocytosis, AIHA).
• Coombs test (DAT): Essential for diagnosing immune-mediated hemolysis (warm/cold AIHA).
• G6PD deficiency: Oxidative stress (drugs, fava beans) induces acute hemolysis; Heinz bodies.
• Sickle Cell Anemia: HbS polymerization leads to vaso-occlusion, chronic hemolysis; hydroxyurea is vital.