Prophylactic transfusion of low-dose platelets did not worsen bleeding rates or other adverse events in a clinical trial comparing three different platelet doses for patients with hypoproliferative thrombocytopenia, according to a report in the Feb. 18 issue of the New England Journal of Medicine.
The low-dose approach did decrease the number of platelets transfused per patient, thus potentially conserving the limited supply of these blood components without compromising patient outcomes. However, patients who received low-dose transfusions required more transfusions than did patients receiving standard- or high-dose platelets, which slightly counterbalanced this potential benefit, said Dr. Sherrill J. Slichter of Puget Sound Blood Center and the University of Washington, Seattle, and her associates.
The investigators performed the trial because the optimal dose of platelets in prophylactic transfusions is controversial. Some advocate higher-than-standard doses with the hope of achieving superior hemostasis; others argue for lower-than-standard doses, hoping to achieve comparable hemostasis while conserving the scarce supply of platelets.
“[Our] findings confirm that the dose per prophylactic platelet transfusion ... did not significantly affect bleeding” complications, Dr. Slichter and her colleagues said.
In their study, 1,351 patients who were at risk for very low platelet counts were randomly assigned to receive prophylactic low-dose (1.1 platelets x 1011/m2 of body surface area), medium-dose (2.2 x 1011/m2), or high-dose (4.4 x 1011/m2) platelet transfusions when their platelet counts reached the trigger point of 10,000 per mm3 or lower. The medium dose corresponded to the dose that is currently considered the standard for most patients.
The patients in this study were treated at 26 sites across the United States. They were expected to have low platelet counts for 5 days or more because they were undergoing hematopoietic stem-cell transplantation or chemotherapy for hematologic cancers or solid tumors.
The primary end point of the study was bleeding of grade 2 or higher. There were no significant differences among the three study groups in this outcome: A total of 68% patients in the low-dose group, 67% in the medium-dose group, and 69% in the high-dose group had at least one episode of such bleeding.
The three study groups also did not differ in the highest grade of bleeding reached, the number of days of bleeding, the number of days of bleeding before grade 2 was reached, the need for red-cell transfusions, or the number of red-cell transfusions needed.
Some of the study subjects never needed the transfusions. For the subset of 1,272 patients who actually received platelet transfusions, the results were essentially the same, the investigators said (N. Engl. J. Med. 2010;362:600-13).
The total number of platelet transfusions did differ among the three groups, however. The median number of platelet transfusions was significantly higher for the low-dose group (five transfusions per patient) than for both of the other groups (three transfusions per patient).
The number of days until the next transfusion was needed also differed significantly. This interval was 1.1 days in the low-dose group, 1.9 days in the medium-dose group, and 2.9 days in the high-dose group.
Bleeding complications of grade 2 or higher did not differ among the three dosage groups according to their underlying medical condition. Overall, bleeding developed in 79% of recipients of allogeneic hematopoietic stem-cell transplants, in 73% of patients undergoing chemotherapy for hematologic cancers, and in 57% of those undergoing autologous or syngeneic hematopoietic stem cell transplantation.
“In conclusion, when prophylactic transfusions are given after a trigger threshold of 10,000 platelets per cubic millimeter or lower is reached, the platelet dose has no significant effect on the incidence of bleeding in patients with hypoproliferative thrombocytopenia, probably because few platelets are needed to maintain hemostasis,” Dr. Slichter and her colleagues said.
Disclosures: The study was supported by grants from the U.S. National Heart, Blood, and Lung Institute. Dr. Slichter reported receiving grant support from the U.S. Army Medical Research Acquisition Activity, Navigant Biotechnologies Inc., and Pall Corp. Eight of her coauthors disclosed grant support, consulting fees, or other relationships with pharmaceutical companies.
Copyright (c) 2009 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.
《新英格兰医学杂志》(New England Journal of Medicine)2月18日刊载的一篇临床试验报告显示，在再生障碍性血小板减少患者中比较3种不同剂量的血小板，结果表明预防性输注小剂量的血小板并不会增加出血或其他不良事件的发生率。
美国西雅图普吉特海湾血液中心和华盛顿大学的Sherrill J. Slichter博士及其助手说，这种小剂量方案的确可减少每位患者输注的血小板数量，因此可能能够保证这些血液成分的有限供应，同时也不会影响患者的预后。不过，与接受标准剂量或大剂量血小板输注的患者相比，接受小剂量输注的患者所需的输注次数更多，这在一定程度上抵消了其潜在效益。
研究者之所以开展这项试验，是因为血小板预防性输注的最佳剂量一直存在争议。有人提倡采用高于标准剂量的输注方案，以期获得更佳的止血效果；其他人则建议采用低于标准剂量的输注方案，目的是在保证血小板的有限供应的同时达到相似的止血效果。
Slichter博士及其同事说：“我们的研究发现证实了血小板每次预防性输注的剂量并不会显著影响出血性并发症的发生率。”
这项试验将1,351例存在血小板计数极低风险的患者随机分组，当患者的血小板计数达到输注指征，即≤10,000/mm3时，分别接受小剂量(1.1 x 1011/m2 体表面积)、中等剂量(2.2 x 1011/m2)或大剂量(4.4 x 1011/m2)血小板的预防性输注。该中等剂量便是目前公认的针对大部分患者的标准剂量。
该试验的受试者分别在美国的26家试验基地接受治疗。由于这些患者因血癌或实体瘤正在接受造血干细胞移植或化疗，因此预计其血小板计数至少会偏低5天以上。
该试验的主要终点是2级或2级以上出血。从这一结局指标来看，3个试验组之间无显著差异：小剂量组、中等剂量组和大剂量组分别有68%、67%和69%的患者至少出现了一次2级或2级以上出血。
在患者所达到的最高等级的出血事件、出血的天数、达到2级出血之前出血的天数、对红细胞输注的需求或所需的红细胞输注数量等方面，3个试验组之间均无显著差异。
研究者说，部分试验受试者从未有过输血的需求。对由1,272例患者组成的确实接受了血小板输注的患者亚集进行分析，结果也大致相同(N. Engl. J. Med. 2010;362:600-13)。
但3个试验组血小板输注的总次数的确不同。小剂量组血小板输注的中位次数(每例患者输注5次)显著多于另外2组(每例患者输注3次)。
3组患者距离下一次必需输注的天数也显著不同。这一间隔期在小剂量组、中等剂量组和大剂量组中分别为1.1天、1.9天和2.9天。
根据受试者的潜在疾病来划分，3个剂量组2级或2级以上出血性并发症的发生率亦无差异。总共有79%的异基因造血干细胞移植受者、73%的接受血癌化疗的患者以及57%的接受自体或同基因造血干细胞移植的患者出现了这类出血。
Slichter博士及其同事说：“总的来说，当再生障碍性血小板减少患者的血小板计数达到临界点，即≤10,000/mm3时需行预防性输注，此时血小板的输注剂量不会明显影响出血的发生率，这很可能是因为患者只需很少数量的血小板便可维持机体的止血功能。”
声明：该试验由美国国家心肺血液研究所提供的经费资助。Slichter博士声明接受了美国陆军医疗研究采办局、Navigant生物科技公司和Pall 公司提供的研究经费。另外8名作者声明接受了药厂提供的研究经费、咨询费或存在其他利益关系。
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