Recent guidelines and expert consensus reports list splenectomy as a second-line therapy for ITP patients who have failed corticosteroid therapy [6]. However, there has not been a clinical trial to compare splenectomy with other treatments, including no treatment. In addition, splenectomy is irreversible, and there are no preoperative characteristics that can predict response to splenectomy [10]. Thus, it remains unclear which patients should be favorably indicated for splenectomy compared to other second-line therapies, including rituximab, cyclophosphamide, azathioprine, and the newer thrombopoietic agents romiplostim and eltrombopag. Moreover, there is no evidence regarding the optimal timing of splenectomy, because some adult patients may improve spontaneously or over time as a result of treatment [11]. Thus, an international consensus report suggests deferring splenectomy until the chronic phase (>12 months) [12]. In addition, American Society of Hematology (ASH) guidelines suggest treatment with thrombopoietin receptor agonists (TPO-RAs) for patients who have both contraindication to splenectomy and who have failed at least one other therapy before splenectomy [13]. Under these situations, many patients and physicians now prefer to delay or avoid splenectomy when patients relapse after frontline therapy, although the curative potential of splenectomy is superior to that of other available treatments.

It has been thought that the curative potential of splenectomy is superior to that of other available second-line treatments. For instance, Kojouri et al. reported a complete response in 1731 (66%) of 2623 adult patients with follow-up for 1–153 months in a large systematic review [10]. Moreover, Vianelli et al. reported that 180 of 206 (77%) achieved complete response, 26 (11%) achieved response, and 68 (33%) responsive patients relapsed. Eventually, 138 (59%) patients maintained response without any long-term treatment in a retrospective analysis of 233 patients with follow-up over 10 years [14]—most relapses occur during the first year [15]. Furthermore, Mikhael et al. showed that the short-term non-response rate was 8.2% and long-term relapse rate was 43.6 per 1000 patient years, resulting in an approximate 5 year failure rate of 28% in a large systematic review. Thus, splenectomy results in higher initial relapse rates, particularly in the first 2 years after surgery, although the relapse rate may decline over time [16].

It has been evident that asplenic patients are at increased risk of life-threatening infections. In addition, most therapies for ITP are immunosuppressive, which may also increase the risk of infection.

In a retrospective analysis of ITP patients, the cumulative incidence of sepsis was 10.1% in non-splenectomized patients and 11.1% in splenectomized patients, with a median follow-up of 56 months. The cumulative incidence of early sepsis after splenectomy (<90 days) was 2.6%, and that of late sepsis (>90 days) was 8.8%, suggesting that the infection rate remained elevated, even with longer-term follow-up. Predictors of sepsis in ITP patients include age > 60 years, presence of comorbidities, male sex, race, and splenectomy [9]. A historical population cohort study conducting splenectomized ITP patients compared to non-splenectomized ITP patients showed a higher RR for hospital contact-initiated infection within 90 days after splenectomy (RR 2.6); however, this decreased to 1.0–1.4 at >90 days postsplenectomy [19].