A nucleic acid-targeted photochemical treatment (PCT) using amotosalen HCl (S-59) and ultraviolet A (UVA) light was developed to inactivate viruses, bacteria, protozoa, and leukocytes in platelet components. We conducted a controlled, randomized, double-blinded trial in thrombocytopenic patients requiring repeated platelet transfusions for up to 56 days of support to evaluate the therapeutic efficacy and safety of platelet components prepared with the buffy coat method using this pathogen inactivation process. A total of 103 patients received one or more transfusions of either PCT test (311 transfusions) or conventional reference (256 transfusions) pooled, leukoreduced platelet components stored for up to 5 days before transfusion. More than 50% of the PCT platelet components were stored for 4 to 5 days prior to transfusion. The mean 1-hour corrected count increment for up to the first 8 test and reference transfusions was not statistically significantly different between treatment groups (13 100 ؎ 5400 vs 14 900 ؎ 6200, P ‫؍‬ .11). By longitudinal regression analysis for all transfusions, equal doses of test and reference components did not differ significantly with respect to the 1-hour (95% confidence interval [CI], ؊3.1 to 6.1 ؋ 10 9 / L, P ‫؍‬ .53) and 24-hour (95% CI, ؊1.3 to 6.5 ؋ 10 9 /L, P ‫؍‬ .19) posttransfusion platelet count. Platelet transfusion dose, pretransfusion storage duration, and patient size were significant covariates (P < .001) for posttransfusion platelet counts. Clinical hemostasis, hemorrhagic adverse events, and overall adverse events were not different between the treatment groups. Platelet components prepared with PCT offer the potential to further improve the safety of platelet transfusion using technology compatible with current methods to prepare buffy coat platelet components. (Blood. 2003;101: 2426-2433)

The objective of this open label, phase 1-2, multicentre trial was to evaluate the safety of AMG 531, a novel thrombopoiesis-stimulating peptibody, and its effect on platelet counts in adults with immune thrombocytopenic purpura. Four patients were assigned to each of four unit-dose cohorts: 30, 100, 300 or 500 lg, administered subcutaneously on days 1 and 15 (or day 22 if the day 15 platelet count was >50 · 10 9 /l). Safety was assessed by adverse event (AE) monitoring, clinical laboratory studies and antibody assays. Platelet response was defined as a platelet count double the baseline value and between 50 and 450 · 10 9 /l. Sixteen patients (10 women) were enrolled. The 500-lg cohort was discontinued because the first patient's platelet count became unacceptably high. AEs were generally expected and mild or moderate; the most frequent was headache (eight of 16 patients). Two patients experienced serious AEs related to AMG 531 (severe headache and elevated serum lactic dehydrogenase; thrombocytopenia). Platelet responses occurred with all doses and with a dose equivalent to ‡1 lg/kg in eight of 11 patients. In summary, patients tolerated AMG 531 well at the doses tested. No anti-AMG or antithrombopoietin antibodies were detected. Doses equivalent to ‡1 lg/kg increased platelet counts.

SummaryPlasma exchange is the treatment of choice for patients with thrombotic thrombocytopenic purpura (TTP) and results in remission in >80% of the cases. Treatment of patients who are refractory to plasma therapy or have relapsing disease is difficult. Splenectomy has been a therapeutic option in these conditions but its value remains controversial. We report on a series of 33 patients with TTP who were splenectomised because they were plasma refractory (n ¼ 9) or for relapsed disease (n ¼ 24). Splenectomy generated prompt and unmaintained remissions in all except five patients, in whom remission was delayed (n ¼ 4) or who died with progressive disease (n ¼ 1). Four postoperative complications occurred: one pulmonary embolism and three surgical complications. Median follow-up after splenectomy was 109 months (range 28-230 months). The overall postsplenectomy relapse rate was 0AE09 relapses/patient-year and the 10-year relapse-free survival (RFS) was 70% (95% CI 50-83%). In the patients with relapsing TTP, relapse rate fell from 0AE74 relapses/patient-year before splenectomy to 0AE10 after splenectomy (P < 0AE00001). Two patients died from first postsplenectomy relapse. Although these results are based on retrospective data and that the relapse rate may spontaneously decrease with time, we conclude that splenectomy, when performed during stable disease, has an acceptable safety profile and should be considered in cases of plasma refractoriness or relapsing TTP to reach durable remissions and to reduce or prevent future relapses.

PAS 2 and Plasma-Lyte A make important contributions to platelet transfusion quality improvement and give an excellent CCl even after 4 days of storage.