1.
A randomized controlled trial comparing standard- and low-dose strategies for transfusion of platelets (SToP) to patients with thrombocytopenia
Heddle NM, Cook RJ, Tinmouth A, Kouroukis CT, Hervig T, Klapper E, Brandwein JM, Szczepiorkowski ZM, AuBuchon JP, Barty RL, et al
Blood. 2009;113((7):):1564-73.
Abstract
A noninferiority study was performed comparing low-dose and standard-dose prophylactic platelet transfusions. A double-blind randomized controlled trial (RCT) was performed in 6 sites in 3 countries. Thrombocytopenic adults requiring prophylactic platelet transfusion were randomly allocated to standard-dose (300-600 x 10(9) platelets/product) or low-dose (150- < 300 x 10(9) platelets/product) platelets. The primary outcome (World Health Organization [WHO] bleeding > or = grade 2) was assessed daily through clinical examination, patient interview, and chart review. A WHO grade was assigned through adjudication. The Data Safety Monitoring Board stopped the study because the difference in the grade 4 bleeding reached the prespecified threshold of 5%. At this time, 129 patients had been randomized and 119 patients were included in the analysis (58 low dose; 61 standard dose). Three patients in the low-dose arm (5. 2%) had grade 4 bleeds compared with none in the standard-dose arm. WHO bleeding grade 2 or higher was 49. 2% (30/61) in the standard-dose arm and 51. 7% (30/58) in the low-dose group (relative risk [RR], 1. 052; 95% confidence interval [CI], 0. 737-1. 502). A higher rate of grade 4 bleeding in patients receiving low-dose prophylactic platelet transfusions resulted in this RCT being stopped. Whether this finding was due to chance or represents a real difference requires further investigation. These clinical studies are registered on (http://www. clinicaltrials. gov) as NCT00420914.
2.
Assessing the effectiveness of whole blood-derived platelets stored as a pool: a randomized block noninferiority trial
Heddle NM, Cook RJ, Blajchman MA, Barty RL, Sigouin CS, Boye DM, Nelson EJ, Kelton JG
Transfusion. 2005;45((6):):896-903.
Abstract
BACKGROUND Prestorage pooling of whole blood-derived platelets (PLTs) would simplify bacterial detection. This study evaluated the in vivo effect of the prestorage pooling of PLTs stored for up to 5 days, by assessing the corrected count increment (CCI) 18 to 24 hours after transfusion of the product. STUDY DESIGN AND METHODS A randomized block noninferiority design was used. Eligible patients had chemotherapy-induced thrombocytopenia and were considered likely to need at least six PLT transfusions. For every block of two transfusion events, one consisted of PLTs stored individually and then pooled before transfusion, and the other was a product pooled before storage. The primary outcome was categorized as a successful (>4. 5) or unsuccessful ( RESULTS Twenty-three eligible patients received a total of 189 PLT transfusions. The median number of PLT transfusions was 7 (range, 0-27). Eighty-five complete transfusion pairs were used in the primary analysis. The proportions of transfusions leading to a CCI of greater than 4. 5 was identical for both routine and PLTs pooled before storage (45/85=52. 9%; relative risk, 1. 00; lower limit of the one-sided 95% confidence interval [CI], 0. 83). The estimate of the mean difference in CCI between pooled and routine storage (pooled-routine) was -0. 45 (95% CI, -2. 23 to 1. 33; p=0. 63). CONCLUSION These results provide evidence that storage of PLTs as a pool for up to 5 days results in posttransfusion CCIs that are not inferior to PLTs stored individually.
3.
Whole blood derived platelets stored as a pool: a randomized block non-inferiority study
Heddle NM, Cook RJ, Barty R, Sigouin C, Boye D, Blajchman MA, Nelson E, Kelton JG
Vox Sanguinis. 2004;87((Suppl 3):):6. Abstract No. M 14. 05.
4.
Comparison of methods for the analysis of bleeding outcomes in platelet transfusion studies
Cook RJ, Heddle NM, Rebulla P, Sigouin C, Webert K
Transfusion. 2003;43((9S):):31A.. Abstract No. S102-040F.
5.
Methodologic issues in the use of bleeding as an outcome in transfusion medicine studies
Heddle NM, Cook RJ, Webert KE, Sigouin C, Rebulla P
Transfusion. 2003;43((6):):742-752.
Abstract
BACKGROUND Prophylactic platelet transfusions are given to thrombocytopenic patients to prevent bleeding. The benefit of platelet transfusions has frequently been assessed by measuring the count increment; however, more recently, an assessment of bleeding has been used because it is a more clinically relevant outcome measure. The purpose of this study was to identify platelet transfusion trigger studies that used bleeding as an outcome measure, compare and contrast methods used to document bleeding and analyze bleeding outcomes, and identify and discuss methodologic issues to consider when bleeding is used as a study outcome. STUDY DESIGN AND METHODS A systematic search to identify platelet transfusion trigger studies was performed. Relevant articles were reviewed to identify how bleeding data was captured and analyzed, and methodologic considerations were identified. RESULTS Seven articles meeting the predefined entry criteria were identified. Methods used to document bleeding included chart review and clinical assessment. The frequency of assessment and the type of personnel performing the assessment were variable. Four approaches to analysis were identified: descriptive; comparison of the proportions of patients having at least one bleed; comparison of patient days with bleeding expressed as a proportion of the total days at risk of bleeding; and time-to-event (first bleed) analysis. CONCLUSION Methodologic issues for consideration when designing a clinical study with bleeding as the outcome measure included approaches to minimize bias in the documentation and classification of bleeding and selection of an analysis approach that is appropriate to the question being asked. The need for development of a valid and reliable bleeding scale was also identified.