Evidence Lacking for Eliminating Prophylactic Platelet Transfusions

Can cost be lowered by reducing unnecessary transfusions?
February 2013 Vol 6, No 1, Special Issue - Leukemia

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 results of the Noninferiority Trial of Prophylactic Platelet Transfusions (TOPPS) were presented by Simon J. Stanworth, MRCP, FRCPath, DPhil, Hematologist, Department of Transfusion Medicine, John Radcliffe Hospital, Oxford University Hospitals National Health Service Trust, Headington, United Kingdom.

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

The current practice is to give platelets prophylactically to patients when their platelet counts drop below 10,000/µL to protect against bleeding.
The results showed that hemostatic outcomes were comparable for the 2 approaches, and a new recommendation cannot be made at this time, Dr Stanworth said.

“This multicenter study has not shown that a no-prophylaxis platelet transfusion policy is noninferior to prophylaxis,” he pointed out.

No Differences in Bleeding
There were no significant differences between the arms in the period of thrombocytopenia, number of days in the hospital, or in the 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,” Dr 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). There was also no difference in the time to recovery from thrombocytopenia, he reported.

Grades 3 and 4 bleeding were observed in 1 (0.3%) of the 298 patients who had prophylaxis and in 6 (2%) of the 300 patients who lacked prophylaxis. Although this amounted to a 6-fold increased risk, the difference was not significant (P = .13). In the group without prophylaxis, 1 intracranial bleeding event occurred.

In a predefined subgroup analysis, patients were divided into patients who received autologous stem-cell transplant (ASCT) versus those who received “other” approaches. Dr Stanworth pointed out that the benefit of prophylaxis appeared to be most striking in the “other” group. Interestingly, this included more patients with acute myeloid leukemia.

In the group receiving ASCT, which was mainly comprised of patients with lymphoma and myeloma, bleeding occurred in 45% and 47% of patients, respectively. In the “other” group, grades 2 to 4 bleeding occurred in 38% of patients with prophylaxis and in 58% without prophylaxis.

“The role of prophylactic transfusions in autograft patients is less clear,” Dr Stanworth acknowledged.

He noted that the rates of bleeding in the study were high overall, even when patients received platelet infusions, and he suggested that other approaches to the problem should be explored. Dr Stanworth 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?
Although the results were considered a validation of the current standard of care, some experts at ASH commented that many patients receive prophylactic platelet transfusions unnecessarily.

In the ASH Daily News, Andrew D. Leavitt, MD, Professor, Medical Director, Blood and Marrow Transplant Laboratory, Assistant Medical Director, Blood Bank Laboratory Medicine Cellular Therapy, University of California, San Francisco, noted, “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, Dr Leavitt 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,” he said.

“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,” Dr Leavitt noted. “The US healthcare 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.”

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