Diagnosis: Autoimmune Hemolytic Anemia (AIHA)
A positive direct Coombs test with a negative indirect Coombs test indicates immune-mediated hemolysis occurring on the patient's own red blood cells, confirming the diagnosis of autoimmune hemolytic anemia (AIHA). 1
Understanding the Coombs Test Pattern
- Direct Coombs (DAT) positive means antibodies or complement are already bound to the patient's red blood cells, indicating active immune destruction 2, 1
- Indirect Coombs negative means there are no free-floating antibodies in the serum, distinguishing this from alloimmunization scenarios 3, 4
- This pattern is pathognomonic for AIHA, where antibodies are coating the patient's own RBCs causing hemolysis 1
Immediate Diagnostic Workup
Complete the hemolysis panel immediately:
- Lactate dehydrogenase (LDH) - expect elevation 2
- Haptoglobin - expect decreased or undetectable (<25 mg/dL) 2
- Indirect bilirubin - expect elevation (>1.2 mg/dL) 2
- Reticulocyte count - assess bone marrow response 2, 1
- Peripheral blood smear - look for spherocytes 2
Assess severity and complications:
- Complete blood count with differential - determine anemia severity 2
- Platelet count - rule out Evans syndrome or thrombotic microangiopathy 2
- Creatinine and urinalysis - exclude concurrent TMA 2
Identify underlying cause:
- Autoimmune workup: ANA, rheumatoid factor, HLA-B27 1
- Screen for infections: viral/bacterial causes 1
- Review medications - consider drug-induced hemolytic anemia 3
- Consider lymphoproliferative disorders or immune checkpoint inhibitor exposure 3, 1
Initial Management Algorithm
For severe anemia (Hb <8 g/dL):
- Initiate prednisone 1-2 mg/kg/day orally immediately 1
- Hospitalize for close monitoring 1
- Transfuse RBCs only if Hb <7-8 g/dL or symptomatic 2, 1
- Consult hematology and rheumatology urgently 1
- Supplement with folic acid 1 mg daily 1
For moderate anemia (Hb 8-10 g/dL):
- Start prednisone 1 mg/kg/day orally 1
- Monitor hemoglobin weekly 1
- Consider rheumatology consultation 1
- Add folic acid 1 mg daily 1
For mild anemia (Hb ≥10 g/dL):
- Consider lower dose prednisone 0.5-1 mg/kg/day 1
- Monitor with weekly CBC 1
- Complete autoimmune workup 1
Response Assessment and Escalation
Evaluate treatment response after 1-2 weeks:
- Monitor hemoglobin and reticulocyte response weekly until stabilized 1
- If no improvement after 3 weeks of corticosteroids, escalate to second-line therapy 1
Second-line options for steroid-refractory disease:
- Rituximab 1
- Intravenous immunoglobulin (IVIG) 3, 1
- Immunosuppressive agents (mycophenolate mofetate, cyclosporine) 3
- Splenectomy 1
Critical Management Pitfalls
Do not delay treatment while awaiting complete workup - begin corticosteroids immediately once AIHA is confirmed 1
Do not transfuse unnecessarily - RBC transfusion should only be given for Hb <7-8 g/dL or symptomatic anemia, as transfusion can worsen hemolysis 2, 1
Do not miss thrombotic microangiopathy - if thrombocytopenia is present alongside hemolysis, immediately check ADAMTS13 activity and evaluate for TMA, as this requires different management 2
Do not taper corticosteroids prematurely - maintain full dose for 4-6 weeks before initiating slow taper 1
Do not overlook drug-induced causes - review all medications, particularly immune checkpoint inhibitors, which may require permanent discontinuation 3
Do not ignore underlying malignancy or autoimmune disease - complete the autoimmune and infectious workup even as treatment begins 1
Special Considerations
In patients receiving immune checkpoint inhibitors: This pattern may represent an immune-related adverse event requiring permanent discontinuation of immunotherapy and high-dose corticosteroids 3
Coombs-negative AIHA exists: Approximately 40% of immune checkpoint inhibitor-associated AIHA and 2-10% of warm AIHA cases may have negative DAT despite true immune hemolysis 3, 5, 6, 7. However, your scenario describes a positive DAT, confirming the diagnosis.