Letter: Diagnostic challenges in severe autoimmune hemolysis

To the Editor: I read with great interest the article in the March issue by Dr. Iska and colleagues¹ in which they present a diagnostic approach for autoimmune hemolytic anemia. Nevertheless, several aspects related to implementation of diagnostic workflow, turnaround time, and generalizability require further clarification to facilitate accurate interpretation of this approach.

The authors suggest that the extended direct antiglobulin test can diagnose cases missed by routine testing, but there is no clear guidance on when clinicians should refer a patient to a reference laboratory. Specifically, it is unclear at what point strong biochemical signs of hemolysis combined with conflicting serologic test results (inconsistent direct antiglobulin test results or negative eluate tests) should trigger an immediate referral instead of continuing with local tests.²

Also, the article does not adequately discuss the issue of turnaround time for test results. Advanced immunohematologic tests are often conducted at external laboratories, causing delays and leaving clinicians without clear instructions on how to manage patients in the meantime.³ This is specifically challenging for patients experiencing severe or progressive hemolysis and requiring urgent care and treatment.⁴

Lastly, the generalizability of the suggested diagnostic algorithm remains uncertain, as many healthcare centers do not have ready access to advanced tests. In such situations, following a strict stepwise approach may not be feasible. Consequently, clinicians are required to adopt flexible strategies that combine empiric therapy with early patient referrals.⁵

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