03: Hemolytic Anemias

Question 1

Hemolysis

Answer 1

• Premature erythrocyte destruction (usually <7 days).
• Lab markers:
  
  • ↑Lactate dehydrogenase (LDH) (waste product of dead RBCs)
  • ↑Reticulocytes (immature RBCs)
  • ↑Urine hemosiderin (waste of digested Hgb)
  • ↑Indirect bilirubin (Hgb waste)
  • ↓Haptoglobin (binds free Hgb, excreted)

Question 2

Warm antibody

Answer 2

• IgG mediated
• Occasionally fix complement
• Extravascular hemolysis
• Uncommon
• Often idiopathic
• Hepatitis C, autoimmune dz (e.g., Lupus), lymphomas
• Form microspherocytes
• Tx: corticosteroids, **rituximab **(2nd line; wipes out Ab), splenectomy (2nd line), underlying cond.

Question 3

Cold antibody

Answer 3

• IgM-mediated
• Usually fix complement
• Intra and extravascular hemolysis
• Agglutination
• Rare
• Rarely idiopathic
• Mycoplasma, EBV/CMV mononucleosis, lymphomas
• Tx: plasmapheresis (remove circ. IgM), underlying cond.

Question 4

Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency

Answer 4

• Coombs (-) inherited RBC enzyme defect
• Missing enzyme that allows NADPH to reduce glutathione (to mop up free radicals) –> oxidative stress
• Micro: bite cells, blister cells, Heinz bodies (condensed Hgb from oxidation damage)
• Common in Africa, Mediterranean, men
• Triggers:
  
  • Infx
  • Fava beans (high in oxidants)
  • Diabetic ketoacidosis
  • Anti-malarials
  • Sulfa meds
  • ASA
  • Methylene blue
• Do not test for G6PD deficiency during an acute hemolytic episode (G6PD deficient cells are hemolyzed)
• Tx: avoid triggers; transfusion

Question 5

Hereditary spherocytosis/ellitocytosis

Answer 5

• Coombs (-) inherited RBC structure disorders
• Tx: splenectomy (RBCs get stuck in spleen)

Question 6

Thombotic Thrombocytopenic Purpura (TTP)

Answer 6

• Coombs (-) acquired mechanical destruction dz
• Normally, ADAMTS13 (cleaving factor) breaks ultra-large von Willebrand multimers (ULVWM) into vWF.
• In TTP, Ab tags ADAMTS13 for destruction –> ULVWMs (hypercoagulant) bind inside of endothelium –> RBCS sheared as pass through (microangiopathic hemolytic anemia [MAHA]) –> schistocytes
• Diagnostic criteria:
  
  • Fever
  • Anemia (MAHA)
  • Thrombocytopenia (platelets consumed in plugs)
  • Renal failure
  • Neurological dysfunction
• Lab studies:
  
  • Dz activity: CBC + reticulocytes, bilirubin, LDH, haptoglobin, urinalysis
  • End-organ damage: creatinine, troponin, BNP
  • Others: PT, aPTT, HIV, ADAMTS13 (takes a while to re-supply, so administer while diagnosing)
• Tx: steroids (e.g., prednisone), plasma exchange (remove ADAMTS13 Ab, ULVWM, supply ADAMTS13), rituximab (elimante Ab-mediated hemolysis)

Question 7

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Answer 7

• Coombs (-) acquired RBC defect
• Dark urine present in morning (hemolysis)
• Complement-mediated hemolysis
• Failure to synthesize GPI anchor (RBC membrane protein which holds other proteins)
• **CD55/DAF **and CD59/MIRL normally attached via GPI-anchor, block compliment from attacking RBCs
• Anchor loss results in intravascular hemolysis, thrombosis and bone marrow failure
• Tx: transfusion, anticoagulation, growth factors, bone marrow transplant, eculizumab (blocks C5b complement and prevents hemolysis via membrane attack complex [MAC], but expensive)