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To determine the efficacy of splenectomy for treating thrombocytopenia associated with systemic lupus erythematosus (SLE).The role of splenectomy has been controversial in this patient population.Between 1975 and 2001, 25 consecutive adults with SLE underwent splenectomy specifically for thrombocytopenia. Surgical indications, operative mortality and morbidity, and hematological outcomes were followed in both the short-term (first 30 days) and the long-term (last recorded platelet count, last contact, or death). Response to splenectomy was rated as: complete (CR: platelets ≥150 × 109/L for at least 4 weeks), partial (PR: platelets 50–149 × 109/L for at least 4 weeks), or none (NR: platelets < 50 × 109/L at all times). Relapse occurred if platelets fell below 50 × 109/L after CR or PR.Indications for splenectomy included: thrombocytopenia refractory to (64%), dependent on (20%), or patient intolerance of (16%) medical treatments. Perioperative mortality was 0% and morbidity was 24%. After a median of 9.5 years, 9 patients (36%) had died, with only 1 death being secondary to bleeding. Early partial or complete response rate to splenectomy was 88%. After a median follow-up of 6.6 years, 16 (64%) patients had sustained complete or partial response without relapse. Eight (32%) of these patients required adjunctive medical therapy, whereas the other 8 (32%) did not. The remaining 9 (36%) patients relapsed, but 5 (20%) of the 9 patients were subsequently salvaged to at least partial response with further treatments. The overall PR or CR to splenectomy combined with medical therapy was 84%.Splenectomy should be considered safe and efficacious for thrombocytopenia associated with SLE.