Can a 17-year-old female patient with decreasing hemoglobin (Hb) levels, normal platelet count, and no active site of bleeding, who is being treated with polymyxin, anidulafungin, teicoplanin, and meropenem for a lung infection with Klebsiella, have an autoimmune cause for her condition?

Autoimmune Hemolytic Anemia is a Plausible Cause and Should Be Investigated

Yes, autoimmune hemolytic anemia (AIHA) should be strongly considered in this 17-year-old female with decreasing hemoglobin, normal platelets, and no active bleeding site, particularly given her multiple antibiotic exposures including meropenem, which is a known trigger for drug-induced immune hemolytic anemia. 1

Diagnostic Workup Required

The following tests must be obtained to confirm or exclude autoimmune hemolysis 1:

• Direct antiglobulin test (DAT/Coombs test) - the key diagnostic test for AIHA
• Peripheral blood smear - look for spherocytes, schistocytes, or macrocytosis indicating hemolysis
• Reticulocyte count - should be elevated if bone marrow is responding appropriately
• LDH and haptoglobin - LDH elevated and haptoglobin decreased in hemolysis
• Indirect and direct bilirubin - indirect bilirubin rises with hemolysis
• Free hemoglobin in plasma

Drug-Induced Hemolytic Anemia: Critical Consideration

Meropenem is a documented cause of drug-induced immune thrombocytopenia and hemolytic anemia 2. The guideline specifically lists carbapenems (including meropenem), cephalosporins, and penicillins as common drug causes requiring evaluation 1. Given this patient's exposure to meropenem, polymyxin B, teicoplanin, and anidulafungin, drug-induced hemolysis must be ruled out.

The timing is also suggestive - meropenem-induced immune cytopenias typically develop 5-10 days after drug initiation 2.

Additional Autoimmune Considerations

Beyond drug-induced causes, evaluate for 1:

• Infection-related hemolysis - Mycoplasma and other bacterial/viral causes can trigger AIHA
• Underlying autoimmune disease - particularly relevant in a young female patient
• Paroxysmal nocturnal hemoglobinuria (PNH) - requires flow cytometry screening
• G6PD deficiency - can present with hemolysis during infection/drug exposure

Exclude Other Causes of Anemia

Before confirming autoimmune etiology 1:

• DIC panel (PT/INR, fibrinogen, D-dimer) - to exclude consumptive coagulopathy despite normal platelets
• Bone marrow evaluation - if cytopenias persist or worsen, to exclude myelodysplastic syndrome or marrow failure
• Nutritional deficiencies - B12, folate, iron studies, copper
• Occult bleeding - though less likely with normal platelets and no identified source

Management Algorithm

If AIHA is confirmed (positive DAT with evidence of hemolysis) 1:

1. Discontinue the offending drug immediately - particularly meropenem if drug-induced AIHA is suspected
2. For Grade 2 hemolysis (Hb 8-10 g/dL): Start prednisone 0.5-1 mg/kg/day
3. For Grade 3 hemolysis (Hb <8 g/dL):
   • Prednisone 1-2 mg/kg/day (oral or IV)
   • Consult hematology
   • Consider hospital admission if not already admitted
4. Transfuse RBCs judiciously - only to relieve symptoms or maintain Hb 7-8 g/dL in stable patients
5. Add folic acid 1 mg daily to support increased RBC production

Critical Pitfalls to Avoid

• Do not assume bleeding is the only cause of anemia in critically ill patients - hemolysis and bone marrow suppression are common 3, 4
• Do not delay DAT testing - this is the cornerstone diagnostic test and should be obtained urgently 1
• Do not continue suspected offending drugs - meropenem and other antibiotics should be switched if AIHA is confirmed 1, 2
• Monitor for concurrent immune thrombocytopenia (Evans syndrome) - though platelets are currently normal, drug-induced immune cytopenias can affect multiple cell lines 1, 2

Infection Management Considerations

While investigating hemolysis, continue appropriate antimicrobial coverage for Klebsiella pneumonia 1. If meropenem must be discontinued due to suspected drug-induced hemolysis, alternative regimens for multidrug-resistant Klebsiella include polymyxin B (which the patient is already receiving) combined with other agents based on susceptibility testing 1, 5, 6.