Xiangrong He, MD, PhD & Claudia S. Cohn, MD, PhD, both of University of Minnesota, Department of Laboratory Medicine and Pathology.
What is known?
Thrombocytopenia represents a common problem for patients withchronic bone marrow failure disorders, the most common of which are myelodysplastic syndrome (MDS) and anaplastic anemia (AA). In addition to thrombocytopenia, both morphologic and functional platelet abnormalities may be seen in these patients as well. Platelet transfusion support is the primary management option for thrombocytopenia and active bleeding in these patients. Platelets are usually transfused prophylactically at counts less than 10 x 109/L and with higher counts in patients with hemorrhage. As compared with no prophylaxis, prophylactic platelet transfusions have been shown to be superior in reducing moderate to severe bleeding, primarily in people with leukemia. However, the evidence of prophylactic use for platelet transfusions in people with chronic bone marrow failure is lacking. Meanwhile, platelets are a precious resource and platelet transfusion carries many risks. Thus, avoiding unnecessary prophylactic platelet transfusions will have significant financial and safety implications for health services.
What did this paper set out to examine?
The authors set out to to review in thrombocytopenic patients with chronic bone marrow failure, whether prophylactic transfusions are really necessary or whether these patients can be effectively supported with only therapeutic platelet transfusions given with the onset of bleeding. In particular, they wanted to show that a therapeutic-only platelet transfusion strategy is as effective and safe as a prophylactic platelet transfusion strategy for the prevention of clinically significant bleeding in thrombocytopenic patients with primary bone marrow failure disorders.
What did they show?
The review included all patients with MDS, acquired AA, or congenital bone marrow failure disorders that were not being actively treated with a stem cell transplant or intensive chemotherapy. To maximize the number of studies eligible for inclusion, not only randomized controlled trials (RCTs), but good quality non-RCTs, and controlled before-after studies were included. Only one trial met the inclusion criteria for this review. Unfortunately, the trial was incomplete due to an unexpected slow recruiting rate. Therefore, no results were provided by the trial authors. Although the review was unable to make any recommendations on prophylactic platelet transfusion policies for this patient population, it did identify an urgent need for good quality studies in this area.
What are the implications for practice and for future work?
Thrombocytopenia (platelet counts < 10 x 109/L) is one of the most common complications in patients with chronic bone marrow failure. For example, 40% to 65% of MDS patients have thrombocytopenia. Meanwhile, in some Western countries, bone marrow failure is one of the most common underlying reasons for receiving a prophylactic platelet transfusion. However, guidelines on a therapeutic platelet transfusion strategy versus a prophylactic platelet transfusion strategy in this population are still lacking. Due to the absence of relevant data, the current review was not able to reach any conclusions on the safety and efficacy of prophylactic platelet transfusion compared with therapeutic platelet transfusion for patients with chronic bone marrow failure. Nontheless, this review identified a major gap in the literature and underscored the urgency of prioritizing research in this area. In the meantime, platelet transfusions for people with bone marrow disorders should still be managed according to national transfusion guidelines.
BACKGROUND Bone marrow disorders encompass a group of diseases characterised by reduced production of red cells, white cells, and platelets, or defects in their function, or both. The most common bone marrow disorder is myelodysplastic syndrome. Thrombocytopenia, a low platelet count, commonly occurs in people with bone marrow failure. Platetet transfusions are routinely used in people with thrombocytopenia secondary to
bone marrow failure disorders to treat or prevent bleeding. Myelodysplastic syndrome is currently the most common reason for receiving a platelet transfusion in some Western countries. OBJECTIVES To determine whether a therapeutic-only platelet transfusion policy (transfusion given when patient is bleeding) is as effective and safe as a prophylactic platelet transfusion policy (transfusion given to prevent bleeding according to a prespecified platelet threshold) in people with congenital or acquired bone marrow failure disorders. SEARCH METHODS We searched for randomised controlled trials (RCTs), non-RCTs, and controlled before-after studies (CBAs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2017, Issue 9), Ovid MEDLINE (from 1946), Ovid Embase (from 1974), PubMed (e-publications only), the Transfusion Evidence Library (from 1950), and ongoing trial databases to 12 October 2017. SELECTION CRITERIA We included RCTs, non-RCTs, and CBAs that involved the transfusion of platelet concentrates (prepared either from individual units of whole blood or by apheresis any dose, frequency, or transfusion trigger) and given to treat or prevent bleeding among people with congenital or acquired bone marrow failure disorders.We excluded uncontrolled studies, cross-sectional studies, and case-control studies. We excluded cluster-RCTs, non-randomised cluster trials, and CBAs with fewer than two intervention sites and two control sites due to the risk of confounding. We included all people with long-term bone marrow failure disorders that require platelet transfusions, including neonates. We excluded studies of alternatives to platelet transfusion, or studies of people receiving intensive chemotherapy or a stem cell transplant. DATA COLLECTION AND ANALYSIS We used the standard methodological procedures outlined by Cochrane. Due to the absence of evidence we were unable to report on any of the review outcomes. MAIN RESULTS We identified one RCT that met the inclusion criteria for this review. The study enrolled only nine adults with MDS over a three-year study duration period. The trial was terminated due to poor recruitment rate (planned recruitment 60 participants over two years). Assessment of the risk of bias was not possible for all domains. The trial was a single-centre, single-blind trial. The clinical and demographic characteristics of the participants were never disclosed. The trial outcomes relevant to this review were bleeding assessments, mortality, quality of life, and length of hospital stay, but no data were available to report on any of these outcomes.We identified no completed non-RCTs or CBAs.We identified no ongoing RCTs, non-RCTs, or CBAs. AUTHORS' CONCLUSIONS We found no evidence to determine the safety and efficacy of therapeutic platelet transfusion compared with prophylactic platelet transfusion for people with long-term bone marrow failure disorders. This review underscores the urgency of prioritising research in this area. People with bone marrow failure depend on long-term platelet transfusion support, but the only trial that assessed a therapeutic strategy was halted. There is a need for good-quality studies comparing a therapeutic platelet transfusion strategy with a prophylactic platelet transfusion strategy; such trials should include outcomes that are important to patients, such as quality of life, length of hospital admission, and risk of bleeding.