What is the next step in diagnosis and management for a patient, possibly a child, with spherocytes and tear drop cells on a blood smear, suspected of having hemolytic anemia with potential hereditary causes?

Next Step: Urgent Laboratory Workup for Hemolytic Anemia

Immediately obtain a direct antiglobulin test (DAT/Coombs test), complete blood count with platelet count, ADAMTS13 activity level, lactate dehydrogenase, haptoglobin, reticulocyte count, indirect bilirubin, and creatinine to differentiate between life-threatening thrombotic microangiopathy, autoimmune hemolytic anemia, and hereditary spherocytosis. 1

Critical Initial Testing

The presence of both spherocytes and teardrop cells on peripheral smear indicates hemolysis but requires urgent differentiation between immune and non-immune causes, as management differs dramatically and delays can be fatal. 1

Essential Laboratory Tests to Order Now:

• Direct Antiglobulin Test (DAT): This is the single most critical test to distinguish immune from non-immune hemolysis 1, 2, 3
• Complete Blood Count with Differential: Assess for thrombocytopenia, which when combined with hemolysis suggests thrombotic microangiopathy 1
• ADAMTS13 Activity Level: Must be obtained urgently if thrombotic microangiopathy is suspected, as levels <10% indicate thrombotic thrombocytopenic purpura (TTP) requiring immediate plasma exchange 1
• Hemolysis Markers: LDH (elevated), haptoglobin (decreased), indirect bilirubin (elevated), and reticulocyte count (elevated) to confirm active hemolysis 1, 4
• Creatinine: To assess for renal involvement in thrombotic microangiopathy 1

Diagnostic Algorithm Based on Initial Results

If DAT is Positive:

• Primary diagnosis: Autoimmune hemolytic anemia (AIHA) 1, 2
• Review medication history for drug-induced hemolysis 1
• For grade 2 or higher AIHA: administer prednisone 0.5-1 mg/kg/day 1
• For grade 3 or higher: obtain urgent hematology consultation 1

If DAT is Negative:

• Primary concern: Thrombotic microangiopathy (non-immune microangiopathic hemolysis) 1
• Evaluate platelet count and schistocyte presence on smear 1
• If ADAMTS13 <10%: diagnose as TTP and immediately initiate therapeutic plasma exchange without delay 1
• Administer methylprednisolone 1g IV daily for 3 days starting after first plasma exchange 1

If DAT Negative AND No Thrombocytopenia:

• Consider hereditary spherocytosis, especially if family history present 5, 6
• Osmotic fragility testing and EMA binding test can confirm hereditary spherocytosis 6, 4
• Consider pyruvate kinase deficiency if red cell morphology is relatively unremarkable despite hemolysis 7

Critical Management Pitfalls to Avoid

• Do not dismiss thrombotic microangiopathy based on rare schistocytes alone: Schistocyte counts >1% support the diagnosis, but their absence does not exclude early disease 1
• Do not wait for complete workup before initiating plasma exchange if TTP is strongly suspected clinically 1
• Do not transfuse more than minimum necessary units: Transfuse RBCs only to relieve symptoms or achieve hemoglobin 7-8 g/dL in stable, non-cardiac patients 1
• Discuss with blood bank before transfusing if thrombotic microangiopathy is suspected 1

When to Obtain Urgent Hematology Consultation

• Any grade 3 or higher hemolytic anemia 1
• Suspected thrombotic microangiopathy with thrombocytopenia 1
• Unclear etiology after initial workup 1
• Suspected TTP requiring plasma exchange 7, 1