Background: Autoimmune hemolytic anemia (AIHA) is a rare, heterogeneous disorder characterized by premature erythrocyte destruction mediated by autoantibodies. Although corticosteroids are the cornerstone of initial therapy, clinical outcomes vary widely, and there is limited evidence on predictors of response or long-term disease control, especially in real-world settings.

Aims: To identify clinical and laboratory factors associated with complete response (CR) to first-line therapy and with the need for second-line treatment in a cohort of adult patients with AIHA.

Methods: We conducted a retrospective analysis of adult patients (≥18 years) diagnosed with AIHA and treated between January 2015 and March 2025 in a tertiary referral center in Mexico City. Data on demographics, baseline laboratory values, comorbidities, type of AIHA (primary vs. secondary), presence of underlying autoimmune disease, and treatment strategies were collected. Treatment response was classified per 2020 First International Consensus Group definitions. Logistic regression was used to identify predictors of CR to first-line corticosteroids. Cox proportional hazards models were used to evaluate factors associated with time to second-line therapy (rituximab, immunosuppressants, or splenectomy). Thrombotic events, infections, and overall survival (OS) were also assessed.

Results: We included 65 patients with a median age of 40 years (IQR 26–58); 72.3% were female and 55.4% had a coexisting autoimmune disease. Most patients (98.5%) received corticosteroids as initial therapy, with 63.1% receiving high-dose methylprednisolone. Overall, 96.9% achieved a hematologic response (75.4% CR, 21.5% partial response), with a median time to response of 15 days (IQR 7–35).

CR was significantly associated with high-dose methylprednisolone (90.0% vs. 54.2%; OR 7.62, 95%CI 2.06–28.18, p=0.002) and absence of Evans syndrome (83.3% vs. 40.0%; OR 0.13, 95%CI 0.03–0.57, p=0.008). Neither sex, presence of underlying autoimmune disease, nor use of rituximab or other immunosuppressants in first-line therapy were associated with CR.

During follow-up, 33.8% of patients relapsed and 36.9% required second-line treatment. The 2-year and 5-year treatment-free survival rates were 64.6% and 54.3%, respectively. In multivariate Cox regression, an absolute lymphocyte count ≥1000/μL (HR 0.185, 95% CI 0.075–0.459, p<0.001) and use of immunosuppression in first-line therapy (HR 0.214, 95% CI 0.061–0.756, p=0.017) were independently associated with lower risk of progression to second-line treatment. These associations remained significant after adjusting for presence of autoimmune disease.

Thrombotic events occurred in 23.1% of patients, predominantly deep vein thrombosis and pulmonary embolism. Risk factors for thrombosis included age ≥50 years (OR 5.69, p=0.006), hypertension (OR 5.75, p=0.025), and underlying autoimmune disease (OR 4.33, p=0.039). Infection-related complications occurred in 24.6% of patients, most frequently pneumonia, and were associated with underlying cardiac disease (OR 16.00, p=0.011).

Nine patients (13.8%) died during follow-up. The 5-year OS was 87.8%. OS was significantly higher among patients who achieved CR (93.5% vs. 68.6%, p=0.007) and those aged <50 years (97.6% vs. 73.1%, p=0.015). No significant differences in OS were observed by sex, immunosuppressive strategy, or presence of underlying autoimmune disease.

Summary/Conclusion: In this real-world cohort of adults with AIHA, initial treatment with high-dose methylprednisolone and absence of Evans syndrome were strong predictors of complete hematologic response. Early use of immunosuppressive therapy and preserved lymphocyte counts (≥1000/μL) were independently associated with longer treatment-free survival. These findings highlight the relevance of individualized therapeutic decisions from the outset of treatment and suggest potential prognostic markers to guide early clinical stratification in AIHA.

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2025
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