Evidence Lacking for Eliminating Prophylactic Platelet Transfusions

To prevent bleeding related to stem cell transplant or intense induction and conditioning regimens, prophylactic platelet infusion remains the standard of care, according to a study that compared outcomes for patients who received prophylaxis versus those who did not.

The noninferiority TOPPS (Trial of Prophylactic Platelets) trial results were presented at the 54th Annual Meeting of the American Society of Hematology (ASH) by Simon Stanworth, MRCP, FRCPath, DPhil, from John Radcliffe Hospital, Oxford University Hospitals NHS Trust, in the United Kingdom.

Investigators questioned whether a policy of no prophylaxis with platelet transfusions in adults with hematologic malignancies was not worse than (ie, noninferior to) a prophylactic policy of platelet infusion at <10 x 109/L, as judged by World Health Organization grade 2, 3, or 4 bleeding, up to 30 days from randomization. The study included 600 patients with hematologic malignancies and severe thrombocytopenia.

To protect against bleeding, the current practice is to give platelets prophylactically to patients when their platelet counts drop below 10,000/µL.

The findings indicated that hemostatic outcomes were comparable for the 2 approaches, and a new recommendation cannot be made at this time, Stanworth said. “This multicenter study has not shown that a no-prophylaxis platelet transfusion policy is noninferior to prophylaxis.”

No Differences in Bleeding

There were no significant differences between the study arms in period of thrombocytopenia, number of days in the hospital, or number of serious adverse events. Overall, grade 2 to 4 bleeding was seen in 43% of the prophylaxis group and in 50% of the no-prophylaxis group. Most bleeding was grade 2.

“Serious bleeding complications were rare,” Stanworth noted. “The proportion of patients with grade 2 to 4 bleeding was reduced by 7% with prophylactic platelets.”

Significant differences were, however, seen in a couple of end points. Without prophylaxis, patients experienced significantly more days on which bleeding occurred (1.7 days vs 1.2 days; P = .004) and had a shorter time to the first occurrence of bleeding (P = .02). Time to recovery from thrombocytopenia was also no different, he reported.

Grade 3 and 4 bleeds were observed in 1 of 298 (0.3%) patients who had prophylaxis and in 6 of 300 (2%) who lacked prophylaxis. While this amounted to a 6-fold increased risk, the difference was not statistically significant (P = .13). One intracranial bleed occurred in the group without prophylaxis.

In a predefined subgroup analysis, patients were divided into those with autologous stem cell transplant versus “other” approaches. The benefit of prophylaxis appeared to be most striking in the “other” group, Stanworth said. Interestingly, this included more patients with acute myeloid leukemia.

In the autologous transplant group, which mainly comprised lymphoma and myeloma patients, bleeding occurred in 45% without prophylaxis and in 47% with prophylaxis. In the “other” 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,” Stanworth said.

He also noted that the rates of bleeding in the study, overall, were high, even when patients received platelet infusions, and suggested that other approaches to the problem should be explored. He added that factors other than those addressed by prophylactic platelet transfusions are important in assessing bleeding risk in this population.

Can Unnecessary Transfusions Be Eliminated?

While the results were considered a validation of the current standard of care, some experts at ASH commented on the fact that many patients receive prophylactic platelet transfusions unnecessarily.

Writing in the ASH Daily News, Andrew Leavitt, MD, of the University of California San Francisco, observed that “with half of the no-prophylaxis group experiencing no significant bleeding, it is clear that we transfuse many patients unnecessarily,” yet this practice is actually increasing. Although there were no significant differences in outcomes, patients in the prophylaxis group received 61% more transfusions.

Nationwide, approximately 1.5 million transfusions were administered in 1999, and a decade later more than 2 million platelet transfusions were recorded by the US National Blood Collection and Utilization Survey Report, he said. “It is estimated that about two-thirds of the platelet transfusions are for prophylactic use, while approximately one-third are administered to treat bleeding.”

“While product acquisition and infusion costs vary regionally and are difficult to determine, an average total cost of $1000 per platelet transfusion is a reasonable estimate,” Leavitt added. “The US health care system, therefore, spent more than $1.3 billion on prophylactic platelet transfusions in 2008, yet we lack good evidence that prophylactic platelet transfusions provide clinical benefit.”

Reference
Stanworth SJ, 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). A randomized controlled, non-inferiority trial. Presented at: 54th American Society of Hematology Annual Meeting; December 8-11, 2012; Atlanta, GA. Abstract 1.