Splenectomy. For patients who cannot be weaned from steroids or in whom steroid therapy fails, there is no standard therapy. Currently, the 2 main choices are splenectomy or rituximab (anti-CD20) therapy if the patient did not receive it first line. Splenectomy is the classic therapy for warm AIHA. Reported response rates in the literature range from 50% to 80%, with 50% to 60% remaining in remission.12-16 Timing of the procedure is a balance between allowing time for the steroids to work and the risk of toxicity of steroids. In a patient who has low presurgical risk and has either refractory disease or cannot be weaned from high doses of steroids, splenectomy should be done sooner. Splenectomy can be delayed or other therapy tried first in patients who require lower doses of steroids or have medical risk factors for surgery. Most splenectomies are performed via laparoscopy. The small incisions allow for quicker healing, and the laparoscopic approach provides better visualization of the abdomen to find and remove accessory spleens. When splenectomy is performed by experienced surgeons, the mortality rate is low (< 0.5%).17
The most concerning complication of splenectomy is overwhelming post-splenectomy infection (OPSI).18 In adults, the spleen appears to play a minimal role in immunity except for protecting against certain encap-sulated organisms. Splenectomized patients infected with an encapsulated organism (eg, Pneumococcus) will develop overwhelming sepsis within hours. These patients will often have disseminated intravascular coagulation and will rapidly progress to purpura fulminans. Approximately 40% to 50% of patients will die of sepsis even when the infection is detected early. The overall lifetime risk of sepsis may be as high as 1:500. The organism that most commonly causes sepsis in splenectomized patients is Streptococcus pneumoniae, reported in over 50% of cases. Neisseria meningitidis and Haemophilus influenzae have also been implicated in many cases.19 Overwhelming sepsis after dog bites has been reported due to Capnocytophaga canimorsus infections. Patients are also at increased risk of developing severe malaria and severe babesiosis.18
Patients who have undergone splenectomy need to be warned about the risk of OPSI and instructed to report to the emergency department readily if they develop a fever greater than 101°F (38.3°C) or shaking chills. Once in the emergency department, blood cultures should be obtained rapidly and the patient started on antibiotic coverage with vancomycin and ceftriaxone (or levofloxacin if allergic to beta-lactams).20 For patients in remote areas, some physicians will prescribe prophylactic antibiotics to take while they are traveling to a health care provider or even recommend a “standby” antibiotic dose to take while traveling to health care.5 This usually consists of amoxicillin or a macrolide for penicillin-allergic patients.
Patients in whom splenectomy is being planned or considered should be vaccinated for pneumococcal, meningococcal, and influenza infections (Table 2).18 If there is a plan to treat with rituximab, patients should first be vaccinated since they will not be able to mount an immune response after being treated with rituximab.
Third Line
The therapeutic options for patients who do not respond to either splenectomy or rituximab are much less certain.5,6 Although intravenous immune globulin is a standard therapy for ITP, response rates are low in warm AIHA.17 Numerous therapies have been reported in small series, but no clear approach has emerged. Options include azathioprine, cyclophosphamide, mycophenolate, cyclosporine, danazol, and alemtuzumab. Our approach has been to use mycophenolate for patients requiring high doses of steroids or transfusions. Patients who respond to lower doses of steroids may be good candidates for danazol to help wean them off steroids.
