Likely Cause of AIHA in This Patient
The most likely cause of this patient's positive Direct Coombs Test (DCT) and autoimmune hemolytic anemia is her underlying malignancy with progressive disease, specifically the documented interval increase in primary tumor and new lymph nodes on PET CT. 1
Primary Consideration: Malignancy-Associated AIHA
Your patient's AIHA is almost certainly secondary to her progressive cancer, given the temporal relationship between disease progression and hematologic manifestations. 1, 2
- Secondary AIHA occurs in patients with solid tumors and lymphoproliferative disorders, and this patient has clear evidence of progressive intra-abdominal malignancy with new lymphadenopathy 1
- The combination of gemcitabine, cisplatin, and durvalumab suggests treatment for biliary tract or pancreatic cancer, both of which can cause paraneoplastic AIHA 1
- Nearly all cold antibody AIHA cases and a significant proportion of warm antibody AIHA are secondary diseases, with malignancies being a major underlying cause 1
Why Normal Bilirubin, LDH, and Peripheral Smear Don't Exclude AIHA
The absence of typical hemolysis markers does NOT rule out AIHA - this is a critical diagnostic pitfall:
- Up to 25% of AIHA patients present with normal LDH levels despite active hemolysis 3
- Normal bilirubin can occur in compensated hemolysis or when hemolysis is mild to moderate 2
- The peripheral smear may appear normal in early or mild AIHA, particularly before significant spherocyte formation 2
- The positive DCT is the cornerstone diagnostic finding, and in the context of anemia requiring multiple erythropoietin injections, this strongly supports AIHA regardless of other markers 2
Drug-Induced Considerations (Secondary Possibility)
While less likely given the clinical context, consider:
- Durvalumab (anti-PD-L1 immune checkpoint inhibitor) can cause immune-related adverse events including AIHA 4
- However, immune checkpoint inhibitor-induced AIHA typically shows negative or low-level autoantibodies with normal gamma globulins, which may not fit if this patient has elevated immunoglobulins 4
- The temporal relationship with disease progression rather than drug initiation makes malignancy-associated AIHA more probable 1
Clinical Implications for Management
The poor response to standard hematopoietic growth factors (darbepoetin, romiplostim, eltrombopag) and ongoing prednisolone requirement indicates refractory disease:
- Standard therapy efficacy is notably low in secondary AIHA developing in tumor patients 1
- The patient's progressive malignancy with new lymph nodes suggests the AIHA will persist until cancer control is achieved 1
- Sometimes AIHA associated with malignant tumors disappears after successful anti-tumor therapy 1
Recommended Diagnostic Approach
To confirm the diagnosis and guide therapy:
- Verify DCT specificity (IgG vs C3d) to distinguish warm AIHA from cold agglutinin disease, as this fundamentally changes management 2
- Measure serum immunoglobulin levels, particularly IgG, as elevation supports autoimmune etiology 4
- Check reticulocyte count and haptoglobin if not already done - these may be abnormal even when LDH and bilirubin are normal 1, 3
- Consider lymph node biopsy if not already performed to characterize the progressive adenopathy 1
Treatment Strategy
For malignancy-associated AIHA with disease progression:
- Continue prednisolone as first-line therapy, though response rates are lower in secondary AIHA 1
- Consider rituximab (anti-CD20) for refractory warm antibody AIHA, which appears highly effective even in secondary cases 1
- Mycophenolate mofetil is effective in AIHA patients with underlying malignancy 1
- Most importantly, optimize cancer-directed therapy - controlling the underlying malignancy may resolve the AIHA 1