Platelet transfusions are expensive, carry the potential for adverse reactions, and may be ineffective in some clinical situations. Platelets are also a limited resource, dependent on a relatively stressed blood bank infrastructure for supply and distribution. (Refer to Feature in this issue.) Based on recent evidence, the American Society of Clinical Oncology (ASCO) revised their 2001 clinical practice guidelines for platelet transfusions in patients with cancer.
One of the new recommendations identifies patients undergoing autologous hematopoietic stem-cell transplantation (AHSCT) as an exemption to the general rule to provide prophylactic platelet transfusions to patients undergoing therapy for hematologic malignancies. In contrast to allogenic HSCT, therapeutic platelet transfusions (at the first sign of bleeding) for AHSCT was given a moderate strength recommendation based on high-quality evidence. The remainder of this commentary will examine the evidence supporting this change.
First, it is important to review the evidence supporting the ASCO recommendation to administer prophylactic platelet transfusions to patients with thrombocytopenia (<10 × 109/L) secondary to impaired bone marrow function. Two Cochrane reviews from 2015 served as the foundation for this recommendation.1,2 The first Cochrane review compared prophylactic versus therapeutic platelet transfusions in six randomized controlled trials (1978 to 2013) enrolling a total of 1,186 hematology patients undergoing myelosuppressive chemotherapy or HSCT.1 The summary of findings for this review focused on the two highest-quality RCTs3,4 ; however, a formal meta-analysis could not be performed owing to significant statistical heterogeneity between the studies. Instead, the authors looked at the trend in the individual studies and concluded that therapeutic platelet transfusions were associated with an increased risk of clinically significant bleeding (World Health Organization grade 2) but reduced the number of platelet transfusions. There was insufficient evidence to determine a difference in severe or life-threatening bleeding. The quality of the evidence was rated as low to moderate (Grading of Recommendations Assessment, Development, and Evaluation [GRADE] criteria) because of lack of blinding, differences in how bleeding was assessed, and a small number of events.
The second Cochrane review recommended a prophylactic threshold of 10 × 109/L based on studies that evaluated different platelet thresholds.2 Three randomized controlled trials (from 1991 to 2001) compared platelet transfusions based on a standard threshold (10 × 109/L) or a higher threshold (20 or 30 × 109/L) in 499 hematology patients undergoing myelosuppressive chemotherapy or HSCT. There was no evidence of a difference in the risk of clinically significant bleeding events within 30 days between the groups (relative risk, 1.35; 95% CI, 0.95 - 1.90). There was also no difference in the risk of severe or life-threatening bleeding (relative risk, 0.99; 95% CI, 0.52 - 1.88). The quality of the evidence was low (GRADE criteria).
Lastly, results from a single observational study of 125 Jehovah’s Witness patients who underwent AHSCT without transfusion support was reported.5 A total of four bleeding episodes of grade 2 or higher were documented. No bleeding episodes occurred when platelet counts were higher than 5 × 109/L.
In Brief
When the data for aHSCT patients are extracted from the studies described here, the decision to allow the option of a therapeutic platelet transfusion policy in patients undergoing AHSCT is based on a total of 439 patients who did not receive prophylactic platelet transfusions across three studies.3-5 The rate of grade 2 or higher bleeding in this group ranged from 3 percent to 47 percent (with the majority being grade 2). Differences in bleeding assessment and scoring, differences in the time frame for data collection, protocol deviations, and subgroup status makes combining the results of these studies problematic. Several additional older studies have been published, but changes in the treatment of hematologic malignancies over time makes their relevance debatable.
Given the limited supply of platelets, there is certainly a compelling need to reduce the dependence on platelet transfusions. Is the quality of evidence outlined here enough to convince transplant physicians to discontinue prophylactic platelet transfusions in patients undergoing AHSCT? That decision will need to be made by each individual center. In the meantime, it is important to note that the ASCO recommendation for therapeutic platelet transfusions also advises close observation in experienced centers and excludes pediatric patients or patients undergoing invasive procedures or receiving anticoagulants.
References
Competing Interests
Dr. Linkins indicated no relevant conflicts of interest.
