Splenectomy for immune thrombocytopenia: down but not out

Abstract

Splenectomy is an effective therapy for steroid-refractory or dependent immune thrombocytopenia (ITP). With the advent of medical alternatives such as rituximab and thrombopoietin receptor antagonists, the use of splenectomy has declined and is generally reserved for patients that fail multiple medical therapies. Splenectomy removes the primary site of platelet clearance and autoantibody production and offers the highest rate of durable response (50% to 70%) compared with other ITP therapies. However, there are no reliable predictors of splenectomy response, and long-term risks of infection and cardiovascular complications must be considered. Because the long-term efficacy of different second-line medical therapies for ITP have not been directly compared, treatment decisions must be made without supportive evidence. Splenectomy continues to be a reasonable treatment option for many patients, including those with an active lifestyle who desire freedom from medication and monitoring, and patients with fulminant ITP that does not respond well to medical therapy. We try to avoid splenectomy within the first 12 months after ITP diagnosis for most patients to allow for spontaneous or therapy-induced remissions, particularly in older patients who have increased surgical morbidity and lower rates of response, and in young children. Treatment decisions must be individualized based on patients' comorbidities, lifestyles, and preferences. Future research should focus on comparing long-term outcomes of patients treated with different second-line therapies and on developing personalized medicine approaches to identify subsets of patients most likely to respond to splenectomy or other therapeutic approaches.

Figure 1.

The spleen in the pathogenesis of ITP. (A) Autoantibodies bind to antigens on platelets, primarily gpIIb/IIIa, and gpIb/IX. (B) Splenic macrophages expressing FcγR internalize antibody-coated platelets, degrade them, and present platelet glycoprotein-derived peptides to autoreactive CD4⁺ T cells, which on activation interact with B cells through the CD40/CD40L interaction leading to somatic hypermutation and class switching. Autoreactive B cells differentiate into anti-platelet antibody-producing plasma cells that either stay in the spleen or migrate to the blood and bone marrow. (C) Megakaryocytes in the bone marrow express platelet glycoproteins such as gpIIb/IIIa and gpIb/IX, and autoantibodies against these antigens impair platelet production and contribute to megakaryocyte apoptosis. Circulating CD8 positive can also cause thrombocytopenia by direct cytotoxicity (not shown).

Figure 2.

Cumulative prevalence of venous thromboembolic events in ITP patients who underwent splenectomy compared with those who did not. There is an increased rate of VTE in patients with ITP that underwent splenectomy vs those who did not; however, the absolute risk is low in both groups. We included population-based/administrative cohort studies (N = 5) and retrospective (N = 7) and prospective (N = 2) cohort studies that reported outcomes on at least 50 patients with ITP, with a median follow-up >3 months.^,,- For the splenectomy patients in particular, we included only studies that reported late (>3 months) VTE events to minimize selection bias from studies focusing on postoperative portal and splenic vein thrombosis. Time is calculated from date of splenectomy in the splenectomy group and date of enrollment in cohort for the nonsplenectomy group. When only median follow-up was provided, means were approximated as described by Wan et al. Some selection bias is possible because the patients that underwent splenectomy may have had more severe disease than the comparison group.