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根据美国血液学会(ASH)第50届年会暨展览会中发表的大型研究结果，血小板减少(thrombocytopenic)之癌症病患的血小板剂量可以减半，且不会增加出血风险。许多专家预测，这个发现将会改变临床实务。
主要研究者、华盛顿Puget Sound血液中心的Sherrill Slichter医师表示，我们发现较低剂量对病患不会有不良反应；她表示，每次输血使用较少的血小板，将可减少血液的供应需求与降低费用。
Slichter医师在ASH的官方记者会中表示，PLADO研究包括了1,350名病患，本试验的样本数让我们认为这就是我们现在该做的，我建议临床医师减少输血中的血小板剂量，因为这不会有风险。
现任ASH总裁、加州大学圣地牙哥分校医学教授Kenneth Kaushansky医师向Medscape Oncology表示同意，他预测这个试验将会改变临床实务；Slichter医师在这个领域是位备受尊重的先驱，如果她结论表示我们可以降低剂量，那我将乐意遵照此策略。
不过，Kaushansky医师警告，我们必须提出概略的警示，强调此建议仅有关于那些与PLADO试验一致的病患。Slichter医师也提及此点，指出几乎所有的参与者都有血液恶性肿瘤(只有7个病患是实质肿瘤)，70%接受骨髓移植，其他30%进行化学治疗。
华盛顿大学血液科的J. Evans Sadler医师表示，这项发现是重要的，因为它将减少一个令人担心的资源利用，也限制了病患对捐血者提供之血液制品的曝露。Sadler医师并未参与本研究，他是ASH科学计划委员会共同主席，他也预测此结果会改变临床实务。
【等候同侪回顾与发表】
爱荷华大学医院小儿病理科教授Ron Strauss医师向Medscape Oncology表示还不行，他认为必须继续使用标准血小板剂量，直到这些结果通过同侪回顾与发表，因为结论在同侪回顾过程中往往会略为调整。
Strauss医师在一场教育研讨会中提出警示，他认为改变实务风险太大；不过，Slichter医师并不同意，她认为数据强度足以建议改变临床实务。她表示，根据本研究，这是安全的。
安大略McMaster大学的Nancy Heddle小姐表示，我不确定。她也建议临床医师等到研究通过同侪回顾与发表后，才改变临床实务。同一场研讨会中，她发表STOP(Strategies for Transfusion of Platelets)试验的结果，该试验也探讨使用较低剂量的血小板进行输血，不过它包括了不同的病患族群— 化疗导致血小板减少的病患，主要是急性骨髓性白血病(AML)。
STOP试验因为安全顾虑提早停止，低剂量组有3个特殊案例发生等级4出血，Heddle小姐表示，这可能是、也可能不是因为机率。不过，后续分析显示低剂量组没有好处，且倾向有较高的出血比率，但没有统计上的显著意义。然而，她也声明指出，有一个问题是关于出血发生时的等级判断，因为对于使用这些剂量者的出血等级判定有一些不同的意见。
Slichter医师表示，此议题在PLADO试验中并未出现，因为根据每日体检、病患访视、病例回顾、实验室检查结果等资料，使用电脑校正出血等级。
【出血风险没有差异】
PLADO试验将确定血小板减少病患之最佳血小板预防剂量，试验比较了三个不同的剂量：低剂量(1.1× 1011 血小板/m2)、中剂量(2.2 × 1011血小板/m2)与高剂量(4.4 × 1011血小板/m2)；Slichter医师表示，中剂量最接近目前使用的标准剂量。
纳入试验的病患造血障碍性血小板减少(hypoproliferative thrombocytopenia)，血小板数量低于10,000 mL超过5天时将会住院，此时也将启动血小板输血，当血小板数量达到或低于此数量时进行预防性给予。
结果显示，各剂量组之间的出血风险没有显著差异，不论是世界卫生组织的等级2出血(初级终点)，或者是在一些严重案例。Slichter医师表示，不论剂量多少，等级2的出血发生率仍然偏高，约是70%。
【不同血小板输血剂量之间的出血发生率】
|
出血 |
低剂量
|
中剂量
|
高剂量
|
|
等级2, % |
71
|
69
|
70
|
|
等级 3, % |
12
|
9
|
10
|
|
等级 4, % |
3
|
2
|
2
|
ASH 2008: Dose of Platelet Transfusions Can Be Halved
By Zosia Chustecka
Medscape Medical News
The dose of platelets given by transfusion to cancer patients who become thrombocytopenic can be halved without increasing the risk of bleeding, according to the results of a large study reported here at the American Society of Hematology (ASH) 50th Annual Meeting and Exposition. Several experts have predicted that this finding will change clinical practice.
"We have shown that the lower dose is not adverse for the patient," said lead researcher Sherrill Slichter, MD, from the Puget Sound Blood Center, in Seattle, Washington. Using fewer platelets per transfusion would reduce the demand on the blood supply and should also reduce costs, she said.
The PLADO study involved 1350 patients, and "the size of this trial permits us to say that this is what we should be doing now," Dr. Slichter commented at an official ASH press conference. "I will be recommending that clinicians reduce the dose of platelets in transfusions, as the risk is not there."
Current ASH president Kenneth Kaushansky, MD, professor of medicine at the University of California, San Diego, told Medscape Oncology that he agrees, and predicted that this trial will change clinical practice. "Dr. Slichter is a pioneer in this area and is very well respected. If she concludes that we can lower the dose of platelets, then I am more than willing to go with that strategy," he said.
If she concludes that we can lower the dose of platelets, then I am more than willing to go with that strategy.
However, Dr. Kaushansky cautioned that "we must guard against generalization," and emphasized that the recommendation pertains only to patients comparable to those in the PLADO trial. Dr. Slichter also made this point, and noted that nearly all the participants had hematological malignancies (only 7 patients had solid tumors), 70% had undergone bone-marrow transplants, and the remaining 30% were treated with chemotherapy.
"This finding is important because it will decrease the utilization of a scare resource and will also limit the exposure of patients to blood products from donors," commented J. Evans Sadler, MD, PhD, from the Division of Hematology at Washington University, in St. Louis, Missouri. Dr. Sadler, who was not involved in the study, is a cochair of the ASH Scientific Program Committee. He, too, predicted that the results will change clinical practice.
Wait for Peer Review and Publication
"Not yet," urged Ron Strauss, MD, professor of pathology and pediatrics at the University of Iowa Hospital, in Iowa City. "We should continue to use the standard dose of platelets until these results are peer reviewed and published," he commented to Medscape Oncology, adding that conclusions are often tempered in the peer-review process.
Dr. Strauss urged caution during an educational session. "I think it is too risky to change practice," he said. However, Dr. Slichter said that she disagreed, and that she felt the data were robust enough to recommend a change in clinical practice. "It is safe based on this study," she said.
"I am not sure," said Nancy Heddle, MSc, from McMaster University, in Hamilton, Ontario. She also urged clinicians to wait until the study undergoes peer review and publication before implementing changes in clinical practice. At the same session, she presented results from the STOP (Strategies for Transfusion of Platelets) trial, which also investigated the use of a lower dose of platelets for transfusion, although it involved a different patient population — patients with chemotherapy-induced thrombocytopenia, the majority of whom had acute myeloid leukemia.
The STOP trial was stopped early because of safety concerns, in particular 3 cases of grade?4 bleeding in the low-dose group, which "may or may not be due to chance," said Ms. Heddle. However, further analysis showed no benefit in the low-dose group, and a trend toward a higher burden of bleeding, although this was not statistically significant. She did acknowledge, however, that there was a problem with the adjudication of grading of the bleeding episodes, because there was some disagreement about the grades assigned among those doing the assigning.
This issue did not arise in the PLADO trial, commented Dr. Slichter, because the adjudication of bleeding grades was done by computer, based on data gathered on a daily basis from physical examinations, patient interviews, chart reviews, and laboratory results.
No Difference in Risk of Bleeding
The PLADO trial set out to determine the optimal prophylactic platelet-dose strategy to prevent bleeding in thrombocytopenic patients. It compared 3 different doses of platelets given by transfusion: a low dose (1.1?× 1011 platelets/m2), a medium dose (2.2 × 1011 platelets/m2), and a high dose (4.4 × 1011 platelets/m2). The medium dose corresponds most closely to the standard dose currently used, Dr. Slichter noted.
Patients enrolled in the trial had hypoproliferative thrombocytopenia and were expected to be hospitalized with platelet counts of 10,000?mL or less for more than 5 days. This was the trigger for a platelet transfusion, which was given prophylactically on days when platelet counts reached or fell to below this level.
The results show that there was no significant difference in the risk of bleeding across any of these doses, either in World Health Organization grade?2 bleeding, which was the primary end point, or in the more severe cases. "The incidence of grade?2 bleeding remains high, at around 70%, regardless of dose," Dr. Slichter commented.
Incidence of Bleeding Across Different Doses of Platelet Transfusion
| Bleeding | Low Dose | Medium Dose | High Dose |
| Grade 2, % | 71 | 69 | 70 |
| Grade 3, % | 12 | 9 | 10 |
| Grade 4, % | 3 | 2 | 2 |
In addition, there was no difference in the number of patients who need red blood cell transfusions (4 patients in each of the dose groups). There was 1 bleeding-related death in the high-dose group.
Patients in the low-dose group received more platelet transfusions than those in the other 2 groups — a median of 5 transfusions, compared with 3 in both the medium- and high-dose groups (P?< .0001).
However, patients in the low-dose group received significantly fewer platelets — a median of 9 × 1011 in the low-dose group, compared with 11 × 1011 in the medium-dose group and 20 × 1011 in the high-dose group.
Dr. Slichter commented that the fact that more transfusions were given in the low-dose group did not pose any problem because these patients were hospitalized and had intravenous lines set up already. She also said that this should not affect the cost; previous analyses have suggested that 80% of the cost of a platelet transfusion is made up of the platelets themselves, rather than their administration. Dr. Slichter maintains that using half the standard dose of platelets would result in cost savings, and a formal cost analysis is now underway.
Dr. Slichter has disclosed no relevant financial relationships.
American Society of Hematology (ASH) 50th Annual Meeting and Exposition: Abstract 285. Presented December 6, 2008.