No Rationale for Eliminating Prophylactic Platelet Transfusions in Patients with Hematologic Malignancies 

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Prophylactic platelet transfusions should remain the standard of care for many patients with hematologic malignancies who are thrombocytopenic during intensive treatment or stem cell transplant, investigators of the TOPPS trial (noninferiority Trial Of Prophylactic Platelet transfusionS) concluded.1 The study failed to show noninferiority of no prophylaxis based on prestudy definitions, reported Simon J. Stanworth, MRCP, FRCPath, DPhil, from the John Radcliffe Hospital, Oxford University Hospital National Health Service Trust in the United Kingdom, at the 2012 American Society of Hematology (ASH) Plenary Session.

The current standard practice is to give platelets prophylactically when platelet counts drop below 10,000/µL, but experts have more recently questioned whether this practice is really necessary, and in all subgroups with hematologic malignancies.

German Study

Walter H. Dzik, MD, of Massachusetts General Hospital, Boston, introduced the presentation and noted that TOPPS is the second randomized controlled trial to address the question. The other 2012 study, which involved 391 patients from eight centers in Germany, found a significant difference in grade 2 bleeding: 42% with no prophylaxis dropping to 19% among patients who received prophylactic platelet infusions  (P = .0001).2

In the German study, the effect of prophylaxis for this outcome was “unmistakable,” he said. However, no differences were observed in red blood cell counts per patient, days spent in the hospital, or overall survival. The issue has remained unsettled, according to Dr. Dzik.


The current TOPPS study hypothesized that a no-prophylactic transfusion policy is “as effective and safe” as prophylactic platelet transfusions. It was a randomized, parallel-group, open-label, noninferiority comparison in 600 patients recruited from 14 centers in the United Kingdom and Australia. The study evaluated whether no prophylaxis in adults with hematologic malignancies “is not worse than (ie, noninferior to)” a prophylactic policy that initiated the infusion when platelet count was < 10 × 109/L. The outcome measure was clinically significant bleeding (World Health Organization [WHO] grade 2, 3, or 4) up to 30 days from randomization. The noninferiority margin was defined as a 15% difference in the proportion of patients experiencing the primary outcome.

Adult patients were eligible if they had a hematologic malignancy, were receiving chemotherapy or stem cell transplant, and were expected to be thrombocytopenic for at least 5 days. Patients were randomized to prophylaxis or not, but they could receive platelets therapeutically upon signs or symptoms of bleeding, prior to invasive procedures, or at the physician’s discretion. Primary analysis was by intention to treat.

The analysis found comparable hemostatic outcomes for the two strategies, Dr. Stanworth reported. “This multicenter study has not shown that a no-prophylaxis platelet transfusion policy is noninferior to prophylaxis,” he announced.

Bleeding Rates

Before presenting results for the hemostatic outcomes, Dr. Stanworth indicated there was a significant difference in platelet counts and use of platelet transfusions between the two trial arms.

Overall, grade 2 to 4 bleeding (predominantly grade 2) was seen in 43% of the prophylaxis group and in 50% of the no-prophylaxis group (P value for noninferiority = .06). Without prophylaxis, patients experienced significantly more days on which bleeding occurred (1.7 vs 1.2 days; P = .004) and had a shorter time to the first occurrence of bleeding (P = .02). Patients in the no-prophylaxis group had more days with a WHO grade 2 or above bleed, and a shorter time to first bleed. “This multicenter study has not shown that a no-prophylaxis platelet transfusion policy is noninferior to prophylaxis,” Dr. Stanworth said.

Grade 3 and 4 bleeds were observed in 1 of 298 patients who had prophylaxis (0.3%) but in 6 of 300 (2%) who lacked prophylaxis. This represented a sixfold increased risk; however, the difference was not statistically significant (P = .13). “Serious bleeding complications remain rare,” Dr. Stanworth noted.

One intracranial bleed occurred in the group without prophylaxis. Notably, 2 of 7 patients who developed grade 3 or 4 bleeds had platelet counts > 10 × 109/L at the onset of bleeding; both had acute myeloid leukemia and underwent induction chemotherapy.

There were no significant differences between the arms in duration of thrombocytopenia, number of days in the hospital, or number of serious adverse events.

Subgroup Analysis

In a predefined subgroup analysis, the investigators evaluated patients who had autologous stem cell transplant (SCT) vs “other” treatment approaches, In the autologous SCT group, which mainly comprised lymphoma and myeloma patients, bleeding occurred in 45% of the prophylaxis group and 47% of those without prophylaxis. By contrast the differences between the strategies were most striking in the “other” group. In the non–autologous transplant group, grade 2 to 4 bleeding occurred in 38% with prophylaxis and 58% without prophylaxis. “The role of prophylactic transfusions in autograft patients is less clear, and requires further research” he said.


In summary, “The proportion of patients with grade 2-4 bleeding was reduced by 7% with the prophylactic platelets.” To achieve this reduction, patients in the prophylactic arm received 61% more platelet transfusions. Dr. Stanworth noted that the rates of bleeding in the study, overall, were high, even when patients received prophylactic platelet transfusions, and he suggested that other approaches to the problem should be explored, such as the use of antifibrinolytic drugs. Factors other than those addressed by prophylactic platelet transfusions are clearly important in determining bleeding risk. ■

Disclosure: Drs. Dzik and Stanworth reported no potential conflicts of interest.


1. Stanworth S, Estcourt L, Powter G, et al: The effect of a no-prophylactic versus prophylactic platelet transfusion strategy on bleeding in patients with hematological malignancies and severe thrombocytopenia (TOPPS trial). 2012 ASH Annual Meeting. Abstract 1. Presented December 9, 2012.

2. Wandt H, Schaefer-Eckart K, Wendelin K, et al: Therapeutic platelet transfusion versus routine prophylactic transfusion in patients with haematological malignancies: An open-label, multicentre, randomised study. Lancet 380:1309-1316, 2012.

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