Hemolytic anemia = shortened RBC lifespan (< 120 days) causing anemia with compensatory reticulocytosis. Hallmark labs: elevated LDH, elevated indirect bilirubin, low/undetectable haptoglobin, elevated reticulocyte count. Two categories by mechanism: Intravascular hemolysis (RBCs destroyed in circulation -hemoglobinuria, hemoglobinemia, very low haptoglobin -PNH, TTP, mechanical valve, transfusion reaction, DIC). Extravascular hemolysis (RBCs destroyed by splenic macrophages -splenomegaly, jaundice, no hemoglobinuria -AIHA, hereditary spherocytosis, sickle cell, hypersplenism). The direct Coombs test (DAT) is the critical branch point: positive = antibody on RBCs โ immune hemolysis. Negative = non-immune โ check smear for mechanistic clues.
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Prednisone | 1 mg/kg daily โ taper | PO | First-line for warm AIHA. 70-85% respond. Taper slowly (relapse if too fast). Chronic steroid toxicity limits duration. |
| Rituximab | 375 mg/mยฒ weekly ร 4 | IV | Second-line for warm AIHA, first-line for CAD. Anti-CD20. Screen HBV. Response in 1-3 weeks. |
| Eculizumab | 600 mg IV q7d ร 4 โ 900 mg q14d | IV | PNH -anti-C5 complement inhibitor. Meningococcal vaccine โฅ 2 weeks before. Lifelong therapy. TRIUMPH, 2006 |
Patient: 45F with SLE presenting with fatigue, jaundice, dark urine ร 5 days. Hgb 5.8 (baseline 11.5), retic 14%, LDH 620, haptoglobin < 10, indirect bili 5.1. DAT positive (IgG + C3d). Smear: spherocytes.
Key findings: Warm AIHA, IgG antibodies on DAT, spherocytes from splenic macrophage partial phagocytosis. SLE is the classic autoimmune association. Severe anemia requiring urgent treatment.
Management:
Teaching point: Never withhold transfusion in AIHA because the crossmatch is incompatible. All crossmatches will be incompatible, the autoantibody reacts with all RBCs. Transfused cells are destroyed faster but provide critical oxygen delivery.
Patient: 68M with progressive fatigue and acrocyanosis (blue fingers/toes) in winter. Hgb 8.4, retic 8%, LDH 380, haptoglobin < 10. DAT positive (C3d only, IgG negative). Cold agglutinin titer 1:2048. SPEP: IgM kappa M-spike.
Key findings: Cold agglutinin disease, IgM antibodies bind RBCs at cold temperatures โ complement activation โ intravascular hemolysis. C3d-only DAT is the hallmark. IgM M-spike suggests underlying lymphoproliferative disorder (Waldenstrรถm's, marginal zone lymphoma).
Management:
Teaching point: Cold agglutinin disease is fundamentally different from warm AIHA, steroids don't work, splenectomy doesn't help (complement-mediated destruction is intravascular, not splenic). Treatment targets the B-cell clone producing the IgM.
Patient: 28M of Mediterranean descent with acute onset dark urine, back pain, jaundice 2 days after starting TMP-SMX for UTI. Hgb 7.2 (was 14), retic 2% (inappropriately low acutely), LDH 1200, haptoglobin < 10. DAT negative. Smear: bite cells, Heinz bodies on supravital stain.
Key findings: G6PD deficiency, oxidant stress (TMP-SMX) โ Heinz body formation โ splenic "biting" of Heinz bodies โ bite cells. DAT negative distinguishes from AIHA. Low retic acutely because marrow hasn't responded yet (rises by day 5-7).
Management:
Teaching point: G6PD level during acute hemolysis can be falsely normal because the most deficient cells have already been destroyed. A "normal" level during crisis does NOT exclude G6PD deficiency. Always recheck between episodes.
Mrs. Okafor is a 48-year-old woman with SLE presenting with fatigue, jaundice, and dark urine ร 5 days. Exam: pallor, scleral icterus, mild splenomegaly. Labs: Hgb 6.2 (baseline 11), retic 12%, LDH 580, haptoglobin < 10, indirect bili 4.2. DAT strongly positive (IgG + C3d). Smear: spherocytes.