Steroid-Refractory Warm AIHA: Rituximab or Splenectomy First
A single patient, failing steroid tapers twice over. The disagreement isn't whether she needs second-line therapy — it's whether to reach first for the reversible option or the historically more durable one.
Dolores R. finalized her divorce three months ago after a year of separation she describes, without much elaboration, as "the hardest year and also the right decision," and has leaned harder than usual on the routine of her twenty-two years teaching high school Spanish to get through the days since. Her warm autoimmune hemolytic anemia was diagnosed eight weeks ago after a routine physical caught a hemoglobin of 8.1 with an unmistakable hemolytic picture — elevated LDH, low haptoglobin, a strongly positive direct antiglobulin test for IgG with no complement component detected, and a peripheral smear showing scattered spherocytes.
A workup for a secondary cause — lupus serologies, a CT scan for an underlying lymphoproliferative process — came back unrevealing, leaving her with primary, idiopathic warm AIHA. She was started on high-dose prednisone with an initial response, but two attempted tapers over the following six weeks have both triggered a hemoglobin drop back below 9, and she is now on her third consecutive month of steroids with the cushingoid weight gain and mood swings to show for it — changes her school colleagues have noticed enough to ask about directly.
Steroid-refractory warm AIHA has two well-established next steps, and the field's own practice has shifted meaningfully in the past decade about which to reach for first. Splenectomy was historically the default second-line therapy, with a real and durable response rate, but carries permanent risks — overwhelming post-splenectomy infection and a lifelong elevated thrombosis risk — that don't attenuate with time the way a course of infusions does. Rituximab has accumulated enough comparable-efficacy data — Birgens and colleagues randomized rituximab plus prednisolone against prednisolone alone and found higher sustained response — that the First International Consensus Meeting on autoimmune hemolytic anemia, published by Jäger and colleagues in 2020, places it ahead of splenectomy in second line. That consensus is written for patients who are not in an urgent, transfusion-dependent crisis, which is precisely where her two failed tapers and stable transfusion-independent status put her.
Which second-line therapy to try first
I'd reach for rituximab before splenectomy here. Response rates between the two are close enough in the current literature that the deciding factor should be which risk we're actually willing to accept — and splenectomy's overwhelming post-splenectomy infection risk and elevated lifelong thrombosis risk are permanent, while rituximab's risks are largely confined to the treatment period itself.
She isn't in a transfusion-dependent crisis right now, which matters — rituximab's slower onset, typically weeks rather than days, is a real trade-off I wouldn't accept in an unstable patient, but it's a reasonable one in her current, non-urgent state.
I'm not arguing against trying rituximab first — I agree the field has moved that direction for good reason. But I'd want her to hear splenectomy's real advantage stated plainly too: it's a single procedure with a durable response in a real majority of patients, versus an infusion course whose remission, when it works, isn't guaranteed to be permanent either.
If rituximab doesn't produce a durable remission, I don't think we should treat splenectomy as a last resort reached reluctantly — it should be presented as a legitimate, well-established second attempt, not a failure state.
Agreed: rituximab started, with a slower prednisone taper run alongside it rather than stopped, given her non-urgent, non-transfusion-dependent status.
Not agreed: how long a trial to allow before moving to splenectomy if her hemoglobin doesn't stabilize — the surgeon wanted a defined checkpoint named to her at the outset rather than an open-ended wait.