Erythropoietin Increases Hemoglobin and Reticulocyte Counts in Patients with Treatment-Refractory AIHA

In patients with autoimmune hemolytic anemia (AIHA) unresponsive to ongoing and/or prior therapies, treatment with erythropoietin (EPO) effectively increased hemoglobin (Hb) and reticulocyte counts, according to findings presented at the 24th Congress of the European Hematology Association.

“Our study showed that EPO is effective in about 70% of patients with AIHA that was refractory to or relapsed following other therapies, including biologic drugs,” study presenter and lead author Bruno Fattizzo, MD, of the Fondazione IRCCS Ca’ Granda Policlinico Hospital in Milan, Italy, told ASH Clinical News. Based on these findings, “clinicians should consider EPO use in both the acute and the chronic AIHA setting.”

The researchers retrospectively collected data from 29 patients with primary and secondary AIHA who were treated at seven centers across Europe. Participants had received either EPO alone or EPO concomitantly with other therapies. Efficacy (including Hb response or changes in hemolytic markers) was evaluated at 15 days and 30 days, then again at three months, six months, and 12 months.

Partial Hb response was defined as a >2 g/dL increase from baseline or an Hb level of >10 g/dL; complete Hb response was defined as an Hb level of >12g/dL). Markers of hemolysis (lactate dehydrogenase [LDH] and reticulocyte counts) also were measured.

In this population, most patients had warm AIHA (n=13; 48.2%), while 12 patients had cold AIHA (41.4%) and two patients had mixed. One patient had direct antiglobulin test–negative AIHA.

Median hematologic parameters at diagnosis were:

  • Hb levels: 7.3 g/dL (range = 4.1-11.8)
  • LDH: 468 U/L (range = 193-6,000)
  • reticulocytes: 122×109/L (range = 57-310)

At time of diagnosis, 74% of patients had severe anemia (Hb <7 g/dL), and most (95%) had inadequate reticulocytosis. All participants received at least one prior therapy, and 69% of patients initiated EPO due to a lack of response to ongoing treatment with steroids (n=15), immunosuppressants (n=4), or sutimlimab (n=1).

After one month of treatment with EPO, patients experienced significant increases in Hb and reticulocyte levels:

  • median Hb increase: 2.15 g/dL (range = 0.2-4.8 g/dL; p<0.001)
  • median reticulocyte increase: 25×109/L (range = 0-220×109/L; p value not reported)

This increase persisted at month three: an Hb improvement of 2.9 g/dL (range = 0-6.6 g/dL; p<0.001) and a reticulocyte count improvement of 49×109/L (range = 0-195×109/L).

Thirteen patients discontinued EPO at last follow-up, due to long-standing complete Hb response (n=6) or no response (n=7).

Most patients experienced a response within 15 days of EPO treatment (64%). However, the investigators could not eliminate the possibility that early responses could have been due to recent or concomitant medications.

The investigators also observed associations between response to EPO and AIHA subtype. For example, 73% of patients with primary AIHA responded to EPO, compared with 33% of patients with secondary AIHA (p value not reported). Individuals with inadequate reticulocytosis also had higher response rates, compared with those with adequate reticulocytosis (76% vs. 50%; p values not reported).

“Surprisingly, EPO was effective at high rates in AIHA, where immune destruction of erythrocytes is thought to be the major mechanism, suggesting that bone marrow compensation is important in this setting,” Dr. Fattizzo explained.

According to these findings, “EPO has a different mechanism of action compared with the other agents used in AIHA, which work by blocking antibody production (such as with rituximab, bortezomib, and T-cell inhibitors), directly stopping hemolysis (such as complement inhibitors and fostamatinib), or both (as with steroids and splenectomy),” Dr. Fattizzo said.

Limitations of the study include its retrospective nature, the variety of EPO schedules used, and the lack of baseline endogenous EPO levels in all patients. “A prospective ad hoc study would be of great value to clarify the best schedule, combination, and the predictors of response to EPO in AIHA,” Dr. Fattizzo concluded.

The authors report no relevant conflicts of interest.


Fattizzo B, Languille L, Levati G, et al. Evidence based use of erythropoietin in patients with autoimmune hemolytic anemia: a multicenter international study. Abstract #S900. Presented at the 24th European Hematology Association Annual Congress, June 15, 2019; Amsterdam, The Netherlands.