How should I approach a presentation on hemolytic anemia to medical providers?

How to Structure a Presentation on Hemolytic Anemia for Medical Providers

Begin your presentation by establishing the diagnostic framework that divides hemolytic anemia into immune versus non-immune causes using the Direct Antiglobulin Test (DAT), as this single test determines the entire subsequent diagnostic and therapeutic pathway. 1

Opening Framework: The DAT-Based Diagnostic Algorithm

Start by explaining that hemolytic anemia is confirmed when laboratory markers show elevated reticulocyte count, elevated lactate dehydrogenase (LDH), decreased or absent haptoglobin, elevated indirect (unconjugated) bilirubin, and characteristic peripheral blood smear findings 1, 2. Emphasize that the DAT must be performed before initiating any treatment to preserve diagnostic accuracy 1.

The Critical First Branch Point

Present the diagnostic algorithm as two distinct pathways:

DAT-Positive (Immune) Hemolysis:

• Autoimmune hemolytic anemia requiring evaluation for secondary causes including lymphoproliferative disorders, autoimmune diseases, infections, and drug-induced hemolysis 1
• First-line therapy is corticosteroids at 1 mg/kg methylprednisolone or equivalent 1
• Consider autoimmune workup including ANA, anti-dsDNA, and ENA panel if systemic autoimmune disease is suspected 1

DAT-Negative (Non-Immune) Hemolysis:

• Hereditary membranopathies such as hereditary spherocytosis and hereditary elliptocytosis 1
• Enzymopathies including pyruvate kinase deficiency and G6PD deficiency 1
• Thrombotic microangiopathies requiring urgent ADAMTS13 activity testing 1
• Paroxysmal nocturnal hemoglobinuria requiring complement inhibitors 1

Key Clinical Pearls to Emphasize

Common Diagnostic Pitfalls:

• Never dismiss thrombotic microangiopathy due to absence of schistocytes, as this finding has low sensitivity 1
• Pyruvate kinase activity can be falsely normal with markedly elevated reticulocyte count, recent blood transfusions, incomplete platelet/leukocyte removal, or kinetically abnormal mutant enzymes 1
• Wait 90-120 days after red blood cell transfusion before performing enzyme assays, as donor RBCs cause false-negative results 1

Urgent Clinical Scenarios:

• When anemia plus thrombocytopenia are present, immediately determine haptoglobin, indirect bilirubin, and LDH levels 1
• ADAMTS13 activity must be obtained urgently if thrombotic microangiopathy is suspected, as severely deficient activity (<10 IU/dL) indicates thrombotic thrombocytopenic purpura requiring urgent plasma exchange 1
• In pediatric patients with diarrhea, obtain stool culture for Shiga toxin-producing E. coli, as STEC-HUS typically appears 4-5 days after diarrhea onset (versus aHUS which appears concomitantly with diarrhea) 3, 1

Advanced Diagnostic Testing Section

Explain that next-generation sequencing gene panels analyzing 68+ hemolytic anemia-related genes represent the gold standard for hereditary hemolytic anemias 1. This is particularly valuable when:

• Enzyme assays are equivocal or confounded by reticulocytosis or recent transfusions 1
• Clinical presentation suggests hereditary causes but initial testing is inconclusive 1
• PKLR gene sequencing is needed to confirm pyruvate kinase deficiency 1

Treatment Algorithm Based on Etiology

Structure this section by specific diagnoses:

Autoimmune Hemolytic Anemia:

• Prednisone 0.5-2 mg/kg/day for moderate to severe cases 4
• Second-line therapies include rituximab, IVIG, cyclosporine A, and mycophenolate mofetil for refractory cases 4
• Taper corticosteroids gradually once hemolysis resolves 4

Drug-Induced Hemolysis:

• Immediately discontinue the suspected causative drug 1, 4
• Administer corticosteroids for moderate to severe cases 4
• Consider plasma exchange for drug-induced thrombotic microangiopathy 4

Hereditary Causes:

• Monitor iron status and consider chelation therapy for pyruvate kinase deficiency 1
• Allogeneic hematopoietic stem cell transplantation is the only curative treatment for congenital erythropoietic porphyria 1

Thrombotic Microangiopathies:

• Urgent plasma exchange for TTP 1
• Complement inhibitors (eculizumab, ravulizumab) for PNH 1
• For atypical HUS, initiating appropriate treatment within 4-8 hours from diagnosis is essential, as delays are associated with worse outcomes 3

Essential Laboratory Panel to Present

Provide the complete initial workup:

• CBC with differential and reticulocyte count 1, 4
• Peripheral blood smear for red cell morphology and schistocytes 1, 4
• LDH, haptoglobin, indirect bilirubin, and free hemoglobin 1, 4
• Direct antiglobulin test (DAT/Coombs test) 1, 4
• Serum electrolytes, BUN, and creatinine to evaluate renal involvement 1
• Liver function tests to assess hepatic contribution 1

Second-tier testing based on DAT results:

• RBC enzyme assays including pyruvate kinase and G6PD activity 1
• Osmotic fragility testing or eosin-5-maleimide (EMA) binding test for membranopathies 1
• PNH flow cytometry screening in appropriate clinical contexts 1
• Serum ferritin, transferrin saturation, and iron studies 1
• Vitamin B12 and folate levels 1