This article is more than 5 years old. Information may no longer be current.
Bleeding rates after platelet transfusion with, without prophylaxis remain high
ATLANTA — More patients with hematologic malignancies who followed a no-prophylaxis platelet transfusion policy had grade 2 to grade 4 bleeds compared with patients who received prophylaxis, according to results presented at the 2012 ASH Annual Meeting and Exposition.
Those patients also had more days with grade 2 or higher bleeding and a shorter time to first bleed than patients who received prophylaxis, the results showed.
Still, rates of bleeding among patients who did undergo prophylactic platelet transfusion remain high, researchers said.
The effectiveness of prophylactic platelets to prevent bleeding in patients with hematologic malignancies is unclear and has not been addressed until recently, even though platelet transfusions have been used in clinical practice for many decades, according to background information in the study.
Simon J. Stanworth, MRCP, FRCPath, DPhil, of John Radcliffe Hospital in Headington, UK, and colleagues conducted a multicenter study to determine whether a policy of no-prophylactic platelet transfusions is as effective and safe as a policy of prophylactic platelet transfusions.
Researchers screened 1,093 patients from 14 UK and Australian hospitals from August 2006 to August 2011 for the randomized, parallel group, open-label, non-inferiority TOPPS trial.
Researchers enrolled 600 adult patients with hematologic malignancy who were receiving chemotherapy or stem cell transplant and were expected to be thrombocytopenic for at least 5 days.
Of those 600 patients, 299 received prophylactic platelet transfusion and 301 received no prophylaxis. Baseline characteristics were similar between the two arms, and 70% of patients in both arms underwent autologous stem cell transplant.
The proportion of patients with clinically significant bleed — defined as grade 2 or higher up to 30 days from randomization — served as the primary endpoint. The non-inferiority margin was defined as a 15% difference in proportion of patients who experienced the primary outcome.
The primary analysis was by intention to treat.
Grade 2 to grade 4 bleed occurred in 151 of 300 patients (50%) in the non-prophylaxis group, compared with 128 of 298 (43%) patients in the prophylaxis group (adjusted difference=8.4%; 90% CI, 1.7-15.2).
Therefore, the study failed to prove that a no-prophylaxis policy is noninferior to — or as good as — prophylaxis, Stanworth and colleagues said.
The time to the first grade 2-4 bleed was significantly shorter in the non-prophylaxis group.
During follow-up, patients in the no-prophylaxis group averaged 1.7 days with a grade 2-4 bleed vs. 1.2 days for patients in the prophylaxis group (RR=1.52; 95% CI, 1.14-2.03).
More grade 3-4 bleeds occurred in the no-prophylaxis group (6 vs. 1), but the difference did not reach statistical significance (OR=6.05; 95% CI, 0.73-279.72).
Only two of the seven patients who experienced grade 3-4 bleeds had platelet counts <10x109/L at the onset of bleeding, according to researchers. Both of those patients were receiving induction chemotherapy for acute myeloid leukemia.
In a predefined subgroup analysis of patients who underwent autologous stem cell transplant, grade 2 to grade 4 bleeding occurred in99 of 210 patients (47%) in the no-prophylaxis group compared with 95 of 210 (45%) of patients in the prophylaxis group.
Researchers observed no significant difference between groups in period of thrombocytopenia, number of serious adverse events or number of days in the hospital.
The findings clearly demonstrate a need for new treatment strategies in supportive care to minimize the burden of bleeding in patients with hematologic malignancies, Stanworth said.
“There are still a high baseline proportion of patients experiencing bleeding, even with prophylaxis,” Stanworth said.
For more information:
Stanworth SJ. Abstract #1. Presented at: the 2012 ASH Annual Meeting and Exposition; Dec. 8-11, 2012; Atlanta.
Disclosure: The researchers report no relevant financial disclosures.
Perspective
Back to Top
This is an important study in blood management because, over the last two decades, we have used a threshold of about 10,000 platelets per microliter for platelet transfusion. This study randomized patients with platelet counts below this threshold to receive or not receive prophylactic platelets. The study was designed as a noninferiority study, although more bleeding occurred in the nontransfusion group and thus the criteria for noninferiority were not met. The nontransfusion group received significantly fewer platelet transfusions, however, and further analysis will be needed to determine whether these findings are applicable to all subgroups. Though initial findings were negative, a reduction in platelet transfusion retains the potential for substantial cost savings and reduced strain on a precious resource.
Perspective
Back to Top
Although one might come away from this presentation concluding that prophylactic platelet transfusions for chemotherapy-associated severe thrombocytopenia is not required — not so fast. Careful perusal of the presented data indicates that patients with acute myeloid leukemia — in contrast to patients with other malignancies — are, in fact, significantly protected from catastrophic bleeds by rigorous platelet replacement (when counts drop to 10,000 or thereabouts). This dichotomy might relate to the deleterious effect of elevated circulating myeloid cells in AML. That is, the adhesion of such cells to endothelium can cause vascular wall injury and, thus, predispose thrombocytopenic AML patients to excessive hemorrhage.