Platelet Transfusion: A Clinical Practice Guideline From the AABB

Approximately 2.2 million platelet doses are transfused annually in the United States (1). A high proportion of these platelet units are transfused prophylactically to reduce the risk for spontaneous bleeding in patients who are thrombocytopenic after chemotherapy or hematopoietic progenitor cell transplantation (HPCT) (13). Unlike other blood components, platelets must be stored at room temperature, limiting the shelf life of platelet units to only 5 days because of the risk for bacterial growth during storage. Therefore, maintaining hospital platelet inventories is logistically difficult and highly resource-intensive (4, 5). Platelet transfusion is associated with several risks to the recipient (Table 1), including allergic reactions and febrile nonhemolytic reactions. Sepsis from a bacterially contaminated platelet unit represents the most frequent infectious complication from any blood product today (8). In any situation where platelet transfusion is being considered, these risks must be balanced against the potential clinical benefits. Table 1. Approximate Per-Unit Risks for Platelet Transfusion in the United States Guideline Focus These guidelines were designed to provide pragmatic recommendations, based on the best available published evidence, about when platelet transfusion may be appropriate in adult patients. For several common clinical situations, we attempted to identify a platelet count threshold below which platelet transfusion may improve hemostasis and above which platelet transfusion is unlikely to benefit the patient. We did not attempt to address all clinical situations in which platelets may be transfused, and these guidelines are not intended to serve as standards. Clinical judgment, and not a specific platelet count threshold, is paramount in deciding whether to transfuse platelets. Target Population These guidelines provide advice for adult patients who are candidates for platelet transfusion. Guideline Development Process The AABB commissioned and funded the development of these guidelines. Panel Composition A panel of 21 experts was convened. Fifteen participants were members of the Clinical Transfusion Medicine Committee of the AABB, all of whom were hematologists or pathologists with expertise in transfusion medicine. Five additional panel members included a neurosurgeon, a cardiac surgeon, a critical care specialist, an anesthesiologist, and a hematologist, representing the American Association of Neurological Surgeons, the Society of Thoracic Surgeons, the Society of Critical Care Medicine, the American Society of Anesthesiologists, and the American Society of Hematology, respectively. The final panel member was a Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodologist. Committee members had no substantial conflicts of interest as defined by the AABB conflict of interest policy. Pursuant to the policy, individual members were required to disclose actual and apparent financial, professional, or personal conflicts (Appendix Table 1). Appendix Table 1. Panel Members' Conflicts of Interest Systematic Review of the Evidence The guidelines were developed on the basis of a recent systematic review of the literature on platelet transfusions, published separately (11). The search strategy is provided in Appendix Table 2. We searched PubMed from 1946 to the first week of April 2013, and the Cochrane Central Register of Controlled Trials and Web of Science from 1900 to the first week of April 2013 (1024 studies identified). An updated search of these databases was done from the first week of April 2013 to the first week of September 2014. Randomized, controlled trials (RCTs) and observational studies (prospective or retrospective cohort studies, casecontrol studies, and those with no control group) were eligible for inclusion. Outcomes of interest included all-cause mortality, bleeding-related mortality, bleeding, and number of platelet units transfused. Although all observational studies meeting the inclusion criteria were reviewed, data from observational studies were not used when more than 2 RCTs addressed a particular question. There were no language restrictions. After exclusions, 17 RCTs and 53 observational studies were included in the final systematic review. Only 1 relevant observational study (12) from the updated search was identified, and evidence from this study did not change our GRADE judgments of evidence quality or recommendation strength. Appendix Table 2. Search Strategy Used for Systematic Review of the Literature Grading of Evidence The GRADE method was used to assess the quality of the evidence and determine the strength of recommendations (13, 14). The recommendations were developed by consensus at an in-person panel meeting. Panel member judgments on 4 GRADE factors (quality of evidence, balance between the intervention's benefits and harms, resource use, and patient values and preferences) and ratings of the strength of recommendations were validated using an online survey tool 1 week after the meeting. Definitions In this guideline, a platelet unit refers to 1 apheresis platelet unit or a pool of 4 to 6 whole bloodderived platelet concentrates, typically containing 3 to 41011 platelets. Thrombocytopenia refers to a platelet count below the lower limit of the normal range used by the laboratory performing the count. Seven platelet trials included in the systematic review (1521) used a variation of the World Health Organization scale (22) to assess patient bleeding outcomes (23). A summary of the modified World Health Organization scale is provided in Table 2 . Table 2. Summary of the Modified WHO Bleeding Scale Clinical Recommendations Clinical Setting 1: Hospitalized Adult Patients With Therapy-Induced Hypoproliferative Thrombocytopenia Recommendations Recommendation 1: The AABB recommends that platelets should be transfused prophylactically to reduce the risk for spontaneous bleeding in adult patients with therapy-induced hypoproliferative thrombocytopenia. The AABB recommends transfusing hospitalized adult patients with a platelet count of 10109 cells/L or less to reduce the risk for spontaneous bleeding. The AABB recommends transfusing up to a single apheresis unit or equivalent. Greater doses are not more effective, and lower doses equal to one half of a standard apheresis unit are equally effective. Quality of evidence: moderate; strength of recommendation: strong. Evidence Summary Three RCTs (n=1047) compared bleeding outcomes in hospitalized patients with radiation and/or chemotherapy-induced hypoproliferative thrombocytopenia assigned to receive or not receive prophylactic platelet transfusions (Appendix Table 3) (19, 21, 24, 25). All patients had hematologic malignancy treated with chemotherapy or HPCT. Prophylactic platelet transfusions were found to significantly reduce the risk for spontaneous grade 2 or greater bleeding (odds ratio [OR], 0.53 [95% CI, 0.32 to 0.87]). Most bleeding events were classified as grade 2. In the 2 largest trials (19, 21), grade 2 or greater bleeding in patients assigned to the group that did not receive prophylaxis occurred more frequently among patients receiving chemotherapy for acute leukemia compared with autologous HPCT recipients (58% vs. 47% [19, 25]; 51% vs. 28% [21]). Appendix Table 3. Prophylactic Platelet Transfusion Versus No Prophylactic Platelet Transfusion in Therapy-Induced Hypoproliferative Thrombocytopenia The threshold platelet count at which platelets should be transfused prophylactically to reduce the bleeding risk in hospitalized patients with therapy-induced hypoproliferative thrombocytopenia was examined in 4 RCTs (n=658) (Appendix Table 4). Patients were assigned to receive prophylactic platelet transfusion for a morning platelet count less than 10109 versus 20109 cells/L (2628) or 30109 cells/L (15). A greater platelet count threshold (20109 or 30109 cells/L) was not associated with a significantly lower incidence of grade 2 or greater bleeding (OR, 0.74 [CI, 0.41 to 1.35]) or bleeding-related mortality (OR, 0.37 [CI, 0.02 to 9.22]). The total number of days with bleeding was greater in the 10109cells/L threshold group. The 10109cells/L threshold was associated with lower platelet usage and fewer transfusion reactions. Appendix Table 4. Higher Versus Lower Platelet Count Thresholds for Prophylactic Platelet Transfusions in Therapy-Induced Hypoproliferative Thrombocytopenia Four RCTs (n=1132) (Appendix Table 5) examined whether prophylactic transfusion of low-dose platelets (defined as approximately one half of the standard dose of 3 to 41011 platelets) would provide hemostasis equal to that of standard-dose platelets in patients with therapy-induced hypoproliferative thrombocytopenia (16, 18, 20, 29). There was no difference in grade 2 or greater bleeding in recipients of standard-dose versus low-dose platelets (OR, 0.91 [CI, 0.70 to 1.19]). High-dose platelets (approximately double the standard dose) were compared with standard-dose platelets in 2 RCTs (n=951) (Appendix Table 6) (17, 18). Prophylactic transfusion of high-dose platelets did not reduce the risk for bleeding compared with standard-dose platelets (OR, 1.05 [CI, 0.79 to 1.40]). Appendix Table 5. Standard-Dose Versus Low-Dose Prophylactic Platelet Transfusions in Therapy-Induced Hypoproliferative Thrombocytopenia Appendix Table 6. High-Dose Versus Standard-Dose Prophylactic Platelet Transfusions in Therapy-Induced Hypoproliferative Thrombocytopenia Rationale for Recommendations Before routine platelet prophylaxis was introduced, severe hemorrhage was a common cause of death among patients receiving high-dose chemotherapy (30, 31). Today, severe hemorrhage is rarely encountered in this setting. The original studies of platelet prophylaxis were done decades ago, and both chemotherapy and supportive care for patients with cancer have changed dramatically over time. Therefore, the randomized trials reported by