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Dose of Prophylactic Platelet Transfusions and Prevention of Hemorrhage
Sherrill J. Slichter, M.D., Richard M. Kaufman, M.D., Susan F. Assmann, Ph.D., Jeffrey McCullough, M.D., Darrell J. Triulzi, M.D., Ronald G. Strauss, M.D., Terry B. Gernsheimer, M.D., Paul M. Ness, M.D., Mark E. Brecher, M.D., Cassandra D. Josephson, M.D., Barbara A. Konkle, M.D., Robert D. Woodson, M.D., Thomas L. Ortel, M.D., Ph.D., Christopher D. Hillyer, M.D., Donna L. Skerrett, M.D., Keith R. McCrae, M.D., Steven R. Sloan, M.D., Ph.D., Lynne Uhl, M.D., James N. George, M.D., Victor M. Aquino, M.D., Catherine S. Manno, M.D., Janice G. McFarland, M.D., John R. Hess, M.D., Cindy Leissinger, M.D., and Suzanne Granger, M.S.

A BS T R AC T
Background
From the Puget Sound Blood Center and University of Washington Medical Center, Seattle (S.J.S., T.B.G.); Brigham and Women’s Hospital (R.M.K.), Children’s Hospital Boston (S.R.S.), and Beth Israel Deaconess Medical Center (L.U.) — all in Boston; New England Research Institutes, Watertown, MA (S.F.A., S.G.); Fairview– University Medical Center, Minneapolis (J.M.); University of Pittsburgh, Pittsburgh (D.J.T.); University of Iowa, Iowa City (R.G.S.); Johns Hopkins University (P.M.N.) and University of Maryland (J.R.H.) — both in Baltimore; University of North Carolina, Chapel Hill (M.E.B.); Emory University, Atlanta (C.D.J., C.D.H.); University of Pennsylvania (B.A.K.) and Children’s Hospital of Philadelphia (C.S.M.) — both in Philadelphia; Blood Center of Wisconsin, Milwaukee, and University of Wisconsin–Madison, Madison (R.D.W., J.G.M.); Duke University, Durham, NC (T.L.O.); Weill College of Cornell University, New York (D.L.S.); Case Western Reserve University, Cleveland (K.R.M.); University of Oklahoma, Oklahoma City (J.N.G.); University of Texas Southwestern Medical Center, Dallas (V.M.A.); and Tulane University Hospital and Clinics, New Orleans (C.L.). Address reprint requests to Dr. Slichter at Puget Sound Blood Center, 921 Terry Ave., Seattle, WA 98104-1256, or at sjslichter@psbc.org. N Engl J Med 2010;362:600-13.
Copyright © 2010 Massachusetts Medical Society.

We conducted a trial of prophylactic platelet transfusions to evaluate the effect of platelet dose on bleeding in patients with hypoproliferative thrombocytopenia.
Methods

We randomly assigned hospitalized patients undergoing hematopoietic stem-cell transplantation or chemotherapy for hematologic cancers or solid tumors to receive prophylactic platelet transfusions at a low dose, a medium dose, or a high dose (1.1×1011, 2.2×1011, or 4.4×1011 platelets per square meter of body-surface area, respectively), when morning platelet counts were 10,000 per cubic millimeter or lower. Clinical signs of bleeding were assessed daily. The primary end point was bleeding of grade 2 or higher (as defined on the basis of World Health Organization criteria).
Results

In the 1272 patients who received at least one platelet transfusion, the primary end point was observed in 71%, 69%, and 70% of the patients in the low-dose group, the medium-dose group, and the high-dose group, respectively (differences were not significant). The incidences of higher grades of bleeding, and other adverse events, were similar among the three groups. The median number of platelets transfused was significantly lower in the low-dose group (9.25×1011) than in the medium-dose group (11.25×1011) or the high-dose group (19.63×1011) (P = 0.002 for low vs. medium, P<0.001 for high vs. low and high vs. medium), but the median number of platelet transfusions given was significantly higher in the low-dose group (five, vs. three in the medium-dose and three in the high-dose group; P<0.001 for low vs. medium and low vs. high). Bleeding occurred on 25% of the study days on which morning platelet counts were 5000 per cubic millimeter or lower, as compared with 17% of study days on which platelet counts were 6000 to 80,000 per cubic millimeter (P<0.001).
Conclusions

Low doses of platelets administered as a prophylactic transfusion led to a decreased number of platelets transfused per patient but an increased number of transfusions given. At doses between 1.1×1011 and 4.4×1011 platelets per square meter, the number of platelets in the prophylactic transfusion had no effect on the incidence of bleeding. (ClinicalTrials.gov number, NCT00128713.)

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Exclusion criteria were as follows: bleeding of grade 2 or higher. Site coordinators gathered the data and submitted the results electronically. use of drugs intended to affect platelet number or function. a panelreactive HLA antibody level of 20% or more. which was reviewed by all authors.org on July 14. Eligibility Criteria 135 kg. Stratification and Randomization Patients were eligible for the study if they were inpatients of any age undergoing hematopoietic stem-cell transplantation or chemotherapy for hematologic cancers or solid tumors and it was expected that they would have platelet counts of 10.org) before or at the time of assessment. idiopathic or thrombotic thrombocytopenic purpura. 2010 n engl j med 362.nejm. but differences in transfusion volume prevented complete blindfebruary 18.org 601 Downloaded from www.4×1011 platelets per square meter per transfusion (low-dose group. 2010 .000 per cubic millimeter10. and for children. or chemotherapy for solid tumor. the medium dose is similar to a standard adult dose with regard to the number of platelets. We conducted a randomized trial of prophylactic platelet transfusions to determine the effects of the dose of platelets on clinical signs of bleeding. and previous enrollment in this platelet-dose trial (PLADO trial). major surgery within the previous 2 weeks.) The data were analyzed with the use of SAS software (version 9. available with the full text of this article at NEJM.3 Higher doses than these could potentially result in superior hemostasis. 2. the two doses prevented bleeding to a similar degree.8 The lead author wrote the first draft of the manuscript and vouches for the completeness and accuracy of the data.1. Adults provided written informed consent. prothrombin and partial-thromboplastin times 1.2 A standard dose for adults is considered to be approximately 3×1011 to 6×1011 platelets.dose of Prophylactic Platelet Tr ansfusions he optimal number of platelets in a prophylactic platelet transfusion is controversial. Additional criteria were a weight of 10 to Body-surface area was calculated from height and weight. Copyright © 2010 Massachusetts Medical Society. and adverse events. In both trials. performance of bedside platelet leukoreduction. A data and safety monitoring board reviewed the data twice a year. Site staff were not told the patient’s assigned dose. see below and the Supplementary Appendix. platelet refractoriness within the past 30 days. Transfusions The blood-transfusion service was given each patient’s assigned dose and the allowable range. and 4. . Treatment-group assignments were balanced within trial sites with the use of dynamic balancing. Stopping boundaries for comparison of the primary end point between each pair of treatment groups were calculated with the use of an alpha spending function similar to O’Brien–Fleming boundaries. according to local criteria.7 T Me thods A subcommittee of the Transfusion Medicine/Hemostasis Clinical Trials Network investigators designed the study and wrote the manuscript.7 nejm. acute promyelocytic leukemia. and high-dose group. ±25% of the assigned dose. autologous or syngeneic hematopoietic stem-cell transplantation.2×1011.000 per cubic millimeter or lower for 5 days or more. by means of computer-generated permuted blocks. and no previous platelet transfusions for thrombocytopenia during the current period of hospitalization. Two randomized trials with limited enrollment — one of 111 patients5 and the other of 119 patients6 — have compared a low dose of platelets to the standard dose. Institutional review boards approved the study. Children provided assent if required by local site policy. with higher grades indicating worse bleeding. days to next transfusion. pregnancy. All rights reserved.11 Patients were randomly assigned in a 1:1:1 ratio. (The study investigators and staff are listed in the Appendix. respectively) — according to four treatment strata12: allogeneic hematopoietic stem-cell transplantation.12 For typical adults.1×1011. according to the World Health Organization (WHO) bleeding scale9 (ranging from grades 1 through 4. a parent or legal guardian provided written informed consent.3 times the upper limit of the normal range or less. changes in the recipient’s post-transfusion platelet count. chemotherapy for hematologic cancer. a fibrinogen level of 100 mg per deciliter or more. or the hemolytic–uremic syndrome. the use of platelet and red-cell transfusions.2).4 but a lower dose might be equally effective while conserving the platelet supply. to receive platelet transfusions of one of three doses — 1. medium-dose group. planned prophylactic transfusion of platelets at platelet counts of more than 10.

7 nejm. pretransfusion and post-transfusion 602 n engl j med 362. retinal bleeding without visual impairment. Other analyses were exploratory.9 (See the Supplementary Appendix for definitions of bleeding grades 0 through 4. hematocrit values. Results were analyzed according to the patient’s treatment assignment. Statistical Analysis Research staff performed daily assessments of bleeding using physical examinations. which required 450 patients per group. All rights reserved. joint bleeding.54 cm) in diameter. two-sided P values of less than 0. or at withdrawal from the study — whichever occurred first. The time to next transfusion and time to bleeding were compared among the groups by means of the log-rank test. and chart reviews for bleeding events. melena. based on qualitycontrol data. an “at-issue” platelet count was obtained to determine the actual dose transfused.org on July 14. at death. all analyses were restricted to data for patients who received at least one platelet transfusion. deep hematoma.017 were considered to indicate statistical significance. spinal-fluid specimens containing microscopic amounts of blood. Platelets were transfused prophylactically if the morning count was 10. hemoptysis. (2. trigger-threshold adherence for each study day. even if platelet transfusions were not received at the assigned dose or were not administered in accordance with the prophylactic transfusion trigger threshold of 10. or bleeding for more than 1 hour at invasive sites. total number of platelets transfused. three nonstudy physicians adjudicated whether bleeding was the cause of death. No other adjustment was made for analyzing multiple outcomes. the mean platelet count per concentrate. For apheresis platelets. The primary end point was bleeding of grade 2 or higher. Clinical Assessments tor indicated possible death from hemorrhage or if a deceased patient had had grade 3 or 4 bleeding. The bleeding data were used to calculate each patient’s daily bleeding grade. was used to determine the number of platelet concentrates to combine. Platelets and red cells were leukoreduced by means of filtration. Study Completion The study was considered to be completed at 30 days after the first platelet transfusion. The patient’s physician could change the transfusion trigger threshold or dose if required by clinical indications. Unless otherwise specified. and number of platelet transfusions.nejm. a single unit. Grade 2 bleeding was defined as oropharyngeal bleeding or epistaxis for more than 30 minutes during a 24-hour period. Adverse Events Information was collected on all serious adverse events and on events commonly associated with transfusion that occurred during transfusion or within 4 hours afterward. Selection of platelets for transfusion to achieve the correct “attempted dose” was specified as follows.9 except they did not perform urine dipstick or stool guaiac tests. secondary end points were the highest grade of bleeding. Local practice determined the indications for red-cell transfusion. regardless of the patient’s assigned dose. HLA-selected platelets were transfused completely to avoid product wastage. or multiple units. Copyright © 2010 Massachusetts Medical Society.5% in the incidence of the primary end point for any pair among the three treatment groups. They also collected data on all bleeding described in the WHO criteria. visible blood in body-cavity fluid without symptoms.000 platelets per cubic millimeter. and hemoglobin levels were also measured.) If an investiga- The primary end point was bleeding of grade 2 or higher. For each transfusion. with a return to study guidelines as soon as possible.org february 18.13 Dose adherence for each transfusion. The study was designed to have a statistical power of 85% to detect an absolute difference of 12. hematemesis. hematochezia. The highest grade of bleeding was compared using an exact version of the Kruskall–Wallis test. Dichotomous end points were compared among the groups with the use of Fisher’s exact test. For pooled platelet concentrates. .000 per cubic millimeter or lower (the “trigger” threshold). abnormal vaginal bleeding consisting of more than spotting. 2010 Downloaded from www. gross hematuria. interviews with patients. To account for the three pairwise comparisons among the three treatment groups.The n e w e ng l a n d j o u r na l of m e dic i n e ing. at hospital discharge. Daily platelet counts. purpura of more than 1 in. blood in bronchopulmonary lavage specimens. after a 10-day period without a platelet transfusion. the platelet count at the time of collection was used to select a partial unit. 2010 .

004 for medium dose vs. Among the 1162 patients.001 for low dose vs. the attempted dose was known for 5384 transfusions in 1162 patients — and there was dose adherence for 86% of these low-dose transfusions.15 (The platelet increment is defined as the post-transfusion platelet count minus the pretransfusion count. and P<0. medium-dose group. 67% in the medium-dose group.7 nejm. and P = 0. The post hoc subgroup analysis of data regarding the primary end point. high dose). 63%. 2010 603 Downloaded from www.000 platelets per cubic millimeter was adhered to on 90%. used a logistic-regression model with an interaction term. Seventy-nine patients did not receive a platelet transfusion.org on July 14. R e sult s Study Population Between 2004 and 2007. however. and corrected count increments were compared among the groups with the use of generalized linear models to account for possible correlations between results within each patient.003 for low dose vs. and 94% of patient-days in the low-dose group. 2010 . adherence with Platelet Dose and Transfusion Trigger Threshold Dose adherence was not required for 210 HLAselected units of platelets and could not be reliably determined for an additional 331 volumereduced units from which plasma was removed by centrifugation after collection. The baseline characteristics of the study patients were well balanced among the three treatment groups (Table 1).83 for low dose vs. and high-dose group. high dose). P = 0. The trigger threshold of 10. medium-dose group. and 25% of patients. medium dose and for low dose vs. respectively. 62%. and 55% of patients in the low-dose. the percentage of patients in each group with at least one episode of bleeding of grade 2 or higher was not significantly different (71%.001 for medium dose vs. and 93% of these high-dose transfusions (P<0. and high-dose groups.nejm. only 3% of patients had a dose change before the onset of bleeding of grade 2 or higher. Overall.001 for low dose vs. 98% of these mediumdose transfusions. medium dose. high dose). All known at-issue doses were within the assigned range for 51%.14. and 70% of transfusions in the low-dose group. platelet increments. and 61% of patients.66 for medium dose vs. and high-dose group.001 for low dose vs.org february 18. respectively (P<0. high dose).01 for low dose vs. and high-dose groups. 26%. respectively) (Table 3). Primary and Secondary End Points In the 1351 patients who underwent randomization. the percentage with at least one episode of bleeding of grade 2 or higher was 68% in the low-dose group. and 86% of patients in the low-dose.007 for low dose vs. and 7% in the high-dose group (P = 0. 92%. the corrected count increment has a numerator of the platelet increment [in cubic millimeters] multiplied by the body-surface area [in square meters] and a denominator of the total number of platelets transfused divided by 1011. 9% in the medium-dose group. . medium dose). with no significant differences among the groups (P = 0. medium dose. respectively (P = 0. Platelet doses based on at-issue platelet counts were within the patient’s assigned range for 71%. according to randomization stratum. and 69% in the high-dose group. respectively (P<0. This result confirms that the platelet-selection procedure usually resulted in transfusions of at-issue doses in the assigned range. respectively (P<0. Overall. high dose. All rights reserved. high dose). medium dose and P<0. 92%. all known attempted doses were in adherence for 79%. Among the 5466 prophylactic platelet transfusions with neither characteristic. The trigger was adhered to on all study days for 53%. Copyright © 2010 Massachusetts Medical Society. medium dose). medium dose and medium dose vs. 80%. but a total of only 7% of patients had a change in the trigger threshold before the onset of bleeding of grade 2 or higher.001 for low dose vs.dose of Prophylactic Platelet Tr ansfusions platelet-counts. Physicians ordered changes in the platelet dose for clinical reasons for 17% of patients in the lowdose group. high dose) (Table 2). Physicians ordered changes in the trigger threshold for clinical reasons for 32%. mediumdose.) Other continuous variables were analyzed with the use of the Wilcoxon rank-sum test. medium-dose.001 for low dose vs. including these patients in the analyses had a negligible effect on the results. respectively (P = 0. Among the 1272 patients who received at least one platelet transfusion. the highest bleeding grade observed was no bleeding or bleeding of grade 1 in 31% n engl j med 362. 69% and 70%. a total of 1351 patients were enrolled at 26 sites.

1 170 162–178 0. of women (%) No.40 185 (43) 84 (19) 56 (13) 33 (8) 14 (3) 7 (2) 53 (12) 0.22 170 161–178 0.02 2 (<1) 3 (1) 2 (<1) 604 n engl j med 362. of pregnancies Median Interquartile range Previous transfusion — no. nontransplantation) therapy for hematologic cancer Chemotherapy or radiation (i.9 1.41 390 (92) 18 (4) 15 (4) 0.11 0.97 3 2–3 110/164 (67) 0.org on July 14. nontransplantation) therapy for solid tumor 173 (41) 138 (33) 104 (25) 202 (48) 91 (22) 39 (9) 24 (6) 16 (4) 5 (1) 40 (10) 1. (%) Male Female Weight — kg Median Interquartile range Height — cm Median Interquartile range Body-surface area — m2 Median Interquartile range Previous pregnancy No.33 2 2–4 120/163 (74) 0.1 243 (58) 174 (42) 0.6–2.33 High Dose (N = 432) P Value. Medium vs.83 267 (62) 165 (38) 0.e. Low vs.82 78 63–91 0.9 1.54 47 30–57 0.69 0. (%) Nonpalpable Enlarged Splenectomized Primary diagnosis — no.00 173 (41) 142 (34) 105 (25) 393 (94) 15 (4) 9 (2) 0.34 78 60–92 0.35 186 (44) 89 (21) 59 (14) 24 (6) 26 (6) 6 (1) 33 (8) 0.13 0. (%) Acute leukemia Lymphoma Myeloma Chronic leukemia Myelodysplasia Solid tumor Other Stratification category — no. (%) Platelets Red cells Spleen status — no.68 0..9 1. According to Treatment Group.75 3 2–4 111/174 (64) 0.44 258 (61) 165 (39) 0.36 1. Characteristic Low Dose (N = 417) Age — yr Median Interquartile range Sex — no.The n e w e ng l a n d j o u r na l of m e dic i n e Table 1. High vs. Low Dose 0. All rights reserved. (%) Allogeneic stem-cell transplantation Autologous or syngeneic stem-cell transplantation Chemotherapy or radiation (i..e. High Dose 0.32 1.96 177 (41) 149 (34) 104 (24) 244 (59) 316 (76) 0.7 nejm.20 51 32–62 0. Medium Dose 0. 2010 Downloaded from www.67 0.62 0.85 P Value.45 240 (56) 314 (73) 0.7–2.40 0.7–2.97 240 (57) 326 (77) 0. Baseline Characteristics of the Study Patients.09 0. Copyright © 2010 Massachusetts Medical Society.nejm. 2010 . .32 0.74 1.1 80 65–92 0.18 50 34–58 0.org february 18.43 Platelet Dose* Medium Dose (N = 423) P Value.43 403 (93) 20 (5) 9 (2) 0./total no.31 170 160–177 0.

(Continued. with data Median — ×10−3/mm3 Interquartile range — ×10−3/mm3 Prothrombin time† No. 1. with data Median — sec Interquartile range — sec Fibrinogen No.1 0.82 428 1.52 413 28.0 0.0 0.57 430 369 283–468 0.0 1.64 419 29. with data Median — ×ULN Interquartile range — ×ULN International normalized ratio No. 4.9 9.7 0. 2.0–1. and high dose.7 9.92 0.1 0.0–31. Medium Dose Platelet Dose* Medium Dose (N = 423) P Value.99 0.64 419 28.98 410 0.0–1.1 26.008 432 35 24–54 0.0 26.0 0.4×1011 platelets per square meter.1 0.2 26.org 605 Downloaded from www.92 0.7 0. with data Median — g/dl Interquartile range — g/dl Hematocrit No. the median number of days of bleeding of grade 2 or higher was 1.1×1011 platelets per square meter of body-surface area.9 0.7 0.2×1011 platelets per square meter. and grade 4 in 2%. There were no significant differences among the three groups for any of these end points.0 26.89 417 355 276–465 0. 2010 nejm.78 430 29. All rights reserved.85–0.0 1. with data Median Interquartile range Partial thromboplastin time No. and february 18.dose of Prophylactic Platelet Tr ansfusions Table 1.0 0.0 411 1.0 0.0 409 357 279–459 0. Low Dose * Platelet doses were as follows: low dose. In each group. Medium vs.99 415 9.29 421 9.0 0.7 one red-cell transfusion.45 415 39 25–62 0.9 0.0–0.nejm.0–0. The median time from randomization to onset of bleeding ranged from 7 to 8 days.0–31.41 432 9.97 391 0.0–0. The median number of red-cell units transfused per patient was 4.1 1. with data Median — % Interquartile range — % Platelet count No. High Dose High Dose (N = 432) P Value.0–10. grade 3 in 8%.07 0.83 419 1.1–10.95 356 0.org on July 14.0 411 29. medium dose.0–32. † ULN denotes upper limit of the normal range.0–31.87 431 28. Copyright © 2010 Massachusetts Medical Society.70 377 0.8 9. A total of 93% of patients received at least n engl j med 362. with data Median — mg/dl Interquartile range — mg/dl Positive for panel-reactive antibody No.79 369 0. Bleeding of grade 2 or higher occurred in 79% of recipients of allogeneic hematopoietic stem-cell transplants.78 P Value.) Characteristic Low Dose (N = 417) Laboratory values Hemoglobin No. of patients. 73% of patients who had hematologic cancers and were undergoing chemotherapy. grade 2 in 59%.0 26.43 421 40 26–66 0.76 0.3–32.99 0.90 0.0–10.99 0.92 0. .86–0.0–1. Low vs.2 0. with data Median — % of lymphocytes tested Interquartile range — % of lymphocytes tested 389 0.0 26. 2010 .85–0. High vs.6–32.

All rights reserved. according to the patient’s morning platelet-count category.nejm. within each of these treatment categories.309 days.org february 18.001 2.2–4.001 392 51 <0.7 nejm.001 380 63 0.001 1320 70 0. Platelet-Dose Adherence and Response to Prophylactic Platelet Transfusions. the platelet dose had no significant effect on bleeding. .1 0. Characteristic Low P Value.001 34 24–48 1.org on July 14.19 2278 71 0.04 380 55 0. The 1272 patients who received at least one transfusion were observed for a total of 24.001 for the comparison of the latter group with each of the first two groups). of transfusions Transfusions within assigned dose range — % Patients who received ≥1 transfusion that was neither HLA-selected nor volume-reduced and had ≥1 transfusions with data on at-issue dose No. High vs. Figure 1 shows the percentage of days on which bleeding of grade 2 or higher occurred. Dose Low vs.7–2. According to Treatment Group.004 381 86 0.9 0.21 1572 <0. Bleeding of grade 2 or higher occurred Table 2.The n e w e ng l a n d j o u r na l of m e dic i n e 57% of patients undergoing autologous or syngeneic hematopoietic stem-cell transplantation (P<0. of transfusions Transfusions within assigned dose range — % Patients who received ≥1 transfusion that was neither HLA-selected nor volume-reduced and had ≥1 transfusions with data on attempted dose No.1 1646 0.08 9 7–12 <0. of patients All transfusions within assigned dose range —% At-issue dose§ Transfusions that were neither HLA-selected nor volume-reduced and for which at-issue dose was known No. of transfusions Days until next transfusion¶ Median Interquartile range No. Medium vs.001 386 92 0.7 1386 0.001 50 33–68 2547 <0.9 1. Copyright © 2010 Massachusetts Medical Society. (N = 417) Medium Dose Dose adherence† Attempted dose‡ Transfusions that were neither HLA-selected nor volume-reduced and for which attempted dose was known No.007 1669 80 <0.001 1708 98 <0. 2010 .001 1912 <0.48 9 7–19 <0. However.02 2333 86 <0.1 2193 0. High Dose High Dose (N = 432) P Value.11 395 79 <0. Low Dose 606 n engl j med 362.001 1343 93 0.06 Platelet Dose* Medium Dose (N = 423) P Value. 2010 Downloaded from www. of patients All transfusions within assigned dose range —% Response to prophylactic platelet transfusions No.9–3.001 1. of transfusions with all data available to calculate 4-hr CCI‖ Pretransfusion platelet count — ×10−3/mm3 Median Interquartile range Post-transfusion platelet count — ×10−3/mm3** Median Interquartile range 22 16–30 9 7–16 <0.

) Characteristic Low P Value. and the median number of days until the next transfusion (1. and 50.002 for low dose vs.9. counts of 6000 to 80. High vs. the median increase in platelet count after transfusion (10. and the CCI. 2010 607 Downloaded from www. the num- n engl j med 362.001 for all comparisons for all end points) (Table 2). medium dose and low dose vs. medium dose. Medium vs.000 in the medium-dose group.001 for platelet counts of >100.000. (Continued.000 per cubic millimeter.dose of Prophylactic Platelet Tr ansfusions Table 2. Copyright © 2010 Massachusetts Medical Society. The “attempted dose” for apheresis platelets was based on the platelet count at the time of collection.001 19 11–30 0. The median number of platelets transfused was 9. 11.000 per cubic millimeter vs. The analysis of days until next transfusion takes into account data censoring at the time of a granulocyte transfusion.001 ** Platelet doses were as follows: low dose. (N = 417) Medium Dose Platelet increment — ×10−3/mm3 Median Interquartile range Post-transfusion CCI — ×10−3/mm3‖ Median Interquartile range * † ‡ § ¶ ‖ 10 5–15 10 5–17 0.000.000) (Fig. and high dose. and 11. based on quality-control data. The “at-issue dose” was based on platelet counts obtained from all products just before distribution from the blood-transfusion service.000. and P<0.000 per cubic millimeter.03 11 6–15 Platelet Dose* Medium Dose (N = 423) P Value. Calculations of the corrected count increment (CCI) require complete data on pretransfusion and post-transfusion counts and total platelet counts at issue. 1.9. respectively). but the results of statistical comparisons are from a generalized linear model that takes into account that for each patient. and 8% of days with morning platelet counts over 100.1×1011 platelets per square meter of body-surface area.7 nejm. The median number of platelet transfusions administered was five in the low-dose group as compared with three in the medium-dose group and three in the high-dose group (P<0. 19. The median 4-hour corrected count increment was 10.000 to 100.001 for platelet counts of ≤5000 per cubic millimeter vs. The unit of analysis is the transfusion. a stem-cell transfusion. 1). and high-dose groups. Dose Low vs. with no significant differences among groups. high dose). Responses to Platelet Transfusions The low-dose. as did four patients in the medium-dose group and seven in the high-dose group.000 in the low-dose group. 2010 . and high-dose groups differed significantly in the median post-transfusion platelet count (22.org february 18. Nine patients in the low-dose group died. was used to determine how many concentrates to pool. High Dose <0. and 38. 13% of days with morning platelet counts from 81.000.001 for platelet counts of 81. medium dose) (Table 3).000 per cubic millimeter.08 10 6–16 <0. on 25% of days with morning platelet counts of 5000 per cubic millimeter or lower.000 to 100. P = 0. counts of 6000 to 80. All rights reserved.98 High Dose (N = 432) P Value.000 per cubic millimeter (P<0. counts of 6000 to 80. 10. medium dose. the platelet increment. We could calculate the total number of platelets transfused per patient for 1000 patients. Here.1. 4. For pooled platelet concentrates.org on July 14. medium-dose.000 per cubic millimeter. or study completion. P<0.001 38 22–54 0. respectively).63×1011 in the lowdose.2×1011 platelets per square meter. 34.000 in the high-dose group. the results for various transfusions may be correlated. actual medians and interquartile ranges are presented for pretransfusion and post-transfusion counts. Adherence to the prophylactic platelet dose was defined as receipt of a dose that was the assigned transfusion dose ±25%. the mean platelet count per concentrate. and 19. Adverse Events There were no significant differences among the three groups in the occurrence of any specific category of serious adverse events or in the percentage of patients who had one or more serious adverse events (Table 4).001 for high dose vs. .000 per cubic millimeter vs.000. medium-dose.001 for low dose vs.4×1011 platelets per square meter.nejm. The post-transfusion platelet count was obtained within 4 hours after transfusion.25×1011. 17% of days with morning platelet counts from 6000 to 80. respectively) (P<0. 1.25×1011. 2. and 2.000. respectively (P = 0. low dose and high dose vs. Low Dose <0. Wheezing during or shortly after transfusion was significantly more common in the high-dose group than in the mediumdose group.

608 n engl j med 362.61–37. of platelets transfused.nejm.25 6. ‡ Analysis of the number of platelet transfusions per patient was limited to data for patients who had no missing data on the number of transfusion events and no missing data on the total number of platelets transfused: 295 patients in the low-dose group.09 0. 2010 . medium dose.94 Platelet Dose* Medium Dose (N = 423) P Value. All rights reserved. per patient Median Interquartile range Total no.2×1011 platelets per square meter.The n e w e ng l a n d j o u r na l of m e dic i n e Table 3.org on July 14. According to Treatment Group. and 397 in the high-dose group.60 69 0.44 0. Characteristic Low P Value. Low Dose * Platelet doses were as follows: low dose. the tradeoffs between number of platelets and number of transfusion events can be assessed.63 10.99–22.62 4 2–8 92 1. High vs. Medium vs. and 359 in the high-dose group.76 <0.00 0. based on at-issue count — ×10−11 Median Interquartile range 9. 2.1×1011 platelets per square meter of body-surface area.00 0. High Dose High Dose (N = 432) P Value.001 3 2–6 <0. 346 in the mediumdose group. 1.001 19.25 4.30 32 59 7 2 0 1. Dose Low vs.90 1 0–4 0. 387 in the medium-dose group.65 30 60 8 2 1 1. 2010 Downloaded from www. Medium (N = 417) Dose Primary end point ≥1 Episode of bleeding of grade 2 or higher — % of patients Secondary end points Highest grade of bleeding during study — % of patients No bleeding or grade 1 Grade 2 Grade 3 Grade 4 Death from hemorrhage — no.002 11.54 71 0.91 5 3–9 0.66 8 3–19 0.71 70 0.4×1011 platelets per square meter. Copyright © 2010 Massachusetts Medical Society.91–17.70 4 2–8 92 0.99 0. 4.7 nejm. † Analysis of the number of red-cell transfusions per patient was limited to data for patients who had at least one red-cell transfusion and who had no missing data on the number of units transfused: 394 patients in the low-dose group.90 7 3–18 1 0–4 0.org february 18.85 7 3–19 30 58 9 3 0 0.09 3 2–6 <0.001 <0. In these patients.91 1 0–4 0. of patients No. Primary and Key Secondary End Points. .001 4 2–8 95 0.12 0.00 0. of days with bleeding of grade 2 or higher Median Interquartile range Days from randomization to onset of bleeding of grade 2 or higher Median Interquartile range Red-cell transfusions ≥1 Transfusion — % of patients Total units per patient† Median Interquartile range Platelet transfusions‡ No. and high dose.55 0.

and high-dose groups. groups. the medium dose was equivalent to rence and number of red-cell transfusions also the standard dose currently used in clinical prac. medium-.309 days during the study period on which patients had both a morning platelet count and information on bleedRevised ARTIST: MRL ing of grade 2 or higher. 2010 . the data from all three Figure has been redrawn and type has been reset. For a bleeding of grade 2 or higher.7 nejm. The three groups did not differ the low-.dose of Prophylactic Platelet Tr ansfusions Days with Bleeding of Grade 2 or Higher (%) 40 35 30 25 20 15 10 5 0 1– 5 6– 10 11 –1 5 16 –2 0 21 –2 5 26 –3 0 31 –3 5 36 –4 0 41 –4 5 46 –5 0 51 –5 5 56 –6 0 61 –6 5 66 –7 0 71 –7 5 76 –8 0 81 –8 5 86 –9 0 91 –9 5 96 –1 00 >1 00 Morning Platelet-Count Category (×10−3/mm3) No. and 70% in and death (2%). Physithe three groups. and the occurtypical adult. Analyses were adjusted to take SIZE 6 col into account that for each patient. cians changed the dose to a nonstudy dose for Study Completion patients in the low-dose group more often than Completion of the study occurred at the time of for those in the medium-dose and high-dose hospital discharge for most patients (71%). 69%. PLEASE NOTE: count category did not differ significantly among the three treatment groups. resignificantly with regard to reasons for study spectively — were not significantly different. Please check carefully. 2010 609 Downloaded from www. therefore. The highest grade of bleeding. JOB: 36207 ISSUE: 2-18-10 ber of deaths did not differ significantly among There were high rates of adherence for platelet doses and transfusion trigger thresholds.nejm. Data are based on the FIGURE: 1 of 1 3rd 24. the elapsing of 30 days from first platelet least one platelet transfusion and had bleeding transfusion (10%). of Days 652 3240 3843 3194 2449 1976 1501 1182 1009 774 677 513 409 358 298 232 192 162 140 139 1369 Figure 1. per prophylactic platelet transfusion. The percentages of patients who received at platelet transfusion for 10 days (in 14% of patients). Days with Bleeding of Grade 2 or Higher in All Three Treatment Groups. according to the morning platelet-count category. The only death from hemorrhagic causes occompletion. The interaction between treatment TYPE: Line Combo 4-C H/T 33p9 effect of the morning plateletgroup and morning platelet-count category was not significant.org february 18. All rights reserved. RETAKE: 1st AUTHOR: Slichter The percentage of days on which patients had bleeding of grade 2 or higher is shown. According to Morning PlateletCount Categories. curred in the high-dose group (from pulmonary hemorrhage).did not differ significantly among the three tice.org on July 14. withdrawal from the study (4%). groups are combined. but the changes were made primarily afcauses of study completion were an absence of ter the onset of bleeding of grade 2 or higher. Each patient-day was treated as a separate unit of analysis. within the n engl j med 362. of grade 2 or higher — 71%. . These findings confirm that the dose and the high dose was twice the medium dose.16 The low dose was half the medium dose. the Discussion number of days of bleeding of grade 2 or higher. This study evaluated the effects of platelet dose the number of days before the occurrence of on hemostasis and transfusion end points. along with the associated 2nd 95% confidence intervals (dashed lines). the results on various days may be correlated. Other groups. indicating that the AUTHOR. Copyright © 2010 Massachusetts Medical Society.

47 0.50 1.33 45 (11) 6 (1) 41 (10) 34 (8) 25 (6) 21 (5) 16 (4) 2 (<1) 4 (1) 1 (<1) 43 (10) 132 (31) 5 (1) 181 (43) 0. 2.29 0.25 0.12 0 3 (1) 2 (<1) 1 (<1) 0 0 4 (1) 14 (3) 0 5 (1) 4 (1) 27 (6) 0. medium dose.56 0.00 0. Patients had a 25% risk of having bleeding of february 18.00 0. .00 P Value.4×1011 platelets per square meter.50 0.50 1.00 0.29 1.25 1.00 1. Low vs.30 0.22 1.004 0.25 0.17 1.54 0. According to Treatment Group.00 0.1×1011 platelets per square meter of body-surface area. of patients (%) Anaphylaxis Bleeding Cardiac event Central nervous system event Deep-vein thrombosis Graft-versus-host disease Infection Pulmonary event Renal failure Veno-occlusive disease of liver Other Any Event occurring during or ≤4 hr after a transfusion — no.00 0.77 0.73 0.78 0. 4.72 0.43 0.00 0.21 0.38 1.73 0.57 0.org on July 14.75 0. High Dose High Dose (N = 432) P Value.05 0.64 0.org Downloaded from www. platelet dose had no significant effect on bleeding in any of these treatment categories.69 0.11 1.84 0.7 undergoing chemotherapy (73%) or those undergoing allogeneic hematopoietic stem-cell transplantation (79%).00 0.12 0.21 0. † Platelet doses were as follows: low dose. and high dose. 2010 nejm.12 0.12 0.20 0. The percentage of patients with bleeding of grade 2 or higher was significantly less among those undergoing autologous or syngeneic hematopoietic stem-cell transplantation (57%) than among those with hematologic cancers who were 610 n engl j med 362.19 0.28 0.nejm.51 0. Adverse Events. ‡ For events occurring during or within 4 hours after a transfusion.00 0.35 0. 1. as has been described previously.42 0.21 0. Low Dose * Patients could have had more than one event.53 0.00 2 (<1) 5 (1) 5 (1) 1 (<1) 0 3 (1) 11 (3) 12 (3) 3 (1) 2 (<1) 3 (1) 36 (8) 0. 2010 . Copyright © 2010 Massachusetts Medical Society.72 0. Medium Dose Platelet Dose† Medium Dose (N = 423) P Value.19 57 (13) 7 (2) 37 (9) 46 (11) 28 (6) 23 (5) 17 (4) 14 (3) 8 (2) 2 (<1) 50 (12) 144 (33) 7 (2) 205 (47) 0.88 1.00 1.77 0.51 0.2×1011 platelets per square meter. All rights reserved.78 0 5 (1) 3 (1) 4 (1) 3 (1) 0 10 (2) 12 (3) 3 (1) 6 (1) 5 (1) 35 (8) 0. of patients (%)‡ Allergic reaction or hypersensitivity Sinus bradycardia Sinus tachycardia Hypertension Hypotension Dyspnea Hypoxia Wheezing Cough Hemolysis Rigors or chills Fever Infection Any event listed 37 (9) 4 (1) 44 (11) 39 (9) 33 (8) 18 (4) 14 (3) 7 (2) 3 (1) 2 (<1) 37 (9) 149 (36) 5 (1) 193 (46) 0.73 0.77 0. Medium vs.* Event Low Dose (N = 417) Serious adverse event — no. High vs.74 0.17 However.55 0.75 0.45 1.62 0.28 0. did not significantly affect bleeding.68 0.The n e w e ng l a n d j o u r na l of m e dic i n e Table 4.17 0.85 0. data were missing for one patient in each of the three treatment groups.11 0. range of doses studied.50 0.

University of Iowa (HL072028).6 the low-dose group also required significantly more transfusions than the standard-dose group. the total number of platelets transfused — 9.e. All rights reserved. 1. Tulane University (HL072274).1 days in the low-dose group. as compared with none in the standard-dose group (3.000 per cubic millimeter). 11. but much larger.000 per cubic millimeter. criteria used for bleeding grade. In our trial. when prophylactic transfusions are given after a trigger threshold of 10.19 Further reductions in the risk of bleeding at platelet counts of 80. The rates of bleeding seen in our trial are higher than those in several other platelet-transfusion trials. have evaluated the use of low-dose platelet transfusions as compared with standard-dose transfusions.3. nejm. These data. and the median increment in the high-dose group (38. such as assessment method. However. the corrected count increment did not differ significantly among the three groups (i.63×1011 for the high n engl j med 362. University of Oklahoma (HL072283). Johns Hopkins University (HL072191).000 per cubic millimeter) was approximately half the median increment in the medium-dose group (19. Children’s Hospital Boston (HL072291). The number of days until the next transfusion also differed significantly among the three groups: 1.nejm. Duke University (HL072289). In conclusion. respectively. only two previously reported randomized trials.18. University of North Carolina (HL072355). University of Pennsylvania (HL072346).25×1011 for the low dose.19 A strategy of low-dose transfusion significantly reduces the quantity of platelets transfused. Puget Sound Blood Center (HL072305).or high-dose group (three transfusions in each group) (P<0. which could preserve these scarce blood components but could also increase the number of platelet transfusions. Lung. Emory University (HL072248). As expected.9 in the medium-dose group. Case Western Reserve University (HL072033).org on July 14.000 platelets per cubic millimeter or lower is reached.000 per cubic millimeter or higher are postulated to be due to an improved clinical status.18.org february 18. Copyright © 2010 Massachusetts Medical Society. and 2. the median number of transfusions per patient was significantly greater in the low-dose group (five transfusions) than in the medium.5. The Strategies for Transfusion of Platelets (SToP) study (NCT00420914)6 was halted because of grade 4 bleeding in three patients in the lowdose group (1. with limited enrollment. smaller studies. the same dose range was used for all patients in each of the two groups.9 in the high-dose group.20-22 The reported incidence of bleeding depends on factors that often differ among studies.0×1011 platelets per transfusion). . Previous reports suggest that endothelial integrity can be maintained with platelet counts of 5000 per cubic millimeter or higher. 2010 . thus reducing bias. University of Maryland (HL072359). An important difference between our study and the SToP study was that we adjusted the dose of platelets for body-surface area. We did not find a significant difference in the incidence of grade 4 bleeding in our similar.000 per cubic millimeter) was approximately twice the increment in the medium-dose group. 2010 611 Downloaded from www. and 19. and the Blood Center of Wisconsin (HL072290). University of Minnesota (HL072072). Massachusetts General Hospital (HL072299). frequency of assessment.7 dose — was significantly different among the three groups. whereas in the SToP study. and mathematical models all suggest that larger doses give higher increments and prolonged intervals until the next transfusion. To our knowledge. consistent data collection was achieved with the use of daily hemostatic assessments performed by research staff who were unaware of the treatment assignments and who followed detailed instructions. A stopping rule of a 5% absolute difference between the two groups in the incidence of grade 4 bleeding was reached after only 58 and 61 patients were enrolled in the low-dose group and the standard-dose group.001 for both comparisons).25×1011 for the medium dose. the platelet dose has no significant effect on the incidence of bleeding in patients with hypoproliferative thrombocytopenia. and Blood Institute of the National Institutes of Health to the Data Coordinating Center at New England Research Institutes (HL072268). Cornell University (HL072196). In the SToP study.0×1011 platelets per transfusion). University of Pittsburgh (HL072331). probably because few platelets are needed to maintain hemostasis. data from other.23-27 However.20 In our study.6 Neither trial showed any significant differences regarding bleeding of any WHO grades — findings similar to those in our study.dose of Prophylactic Platelet Tr ansfusions grade 2 or higher on days on which the morning platelet count was 5000 per cubic millimeter or lower. the median platelet increment after transfusion in the low-dose group (10. and population of patients. Supported by grants from the National Heart. differences in the increment were explained by differences in the number of platelets transfused).0×1011 to 6.5×1011 to 3. as compared with a 17% risk on days with counts from 6000 to 80.. cohort. Bleeding grades were ascertained on the basis of objective criteria.

Cary. receiving consulting fees from Fenwal Laboratories. No other potential conflicts of interest relevant to this article were reported. Kelty. Emory University. Tannock IF.R. George. Dr. Heddle NM. Iowa City: R. D. Strauss. H. Parker. FL: Chapman & Hall/CRC. Zelen M. Anderson. C. Tinmouth A. 1984. et al. 10. Chapel Hill: M. Sloan. Finazzi G. Miller AB.17:863-71. K. C. receiving consulting fees from Fenwal Laboratories and Cerus and lecture fees from Pall. K. Oklahoma City: J. Prophylac- tic platelet transfusions: which dose is the best dose? A review of the literature. Seattle: S. Tulane University Hospital and Clinics.J. A. Harney.131:588-95.gov/ophs/ bloodsafety/2007nbcus_survey. Dr. Boos. Dr. AuBuchon (medical monitor).73:13-22. 3. A.402 patients. C. University of Iowa. Matthews.org on July 14. D. Thornburg. Safah. Dr. 11. et al. Konkle (principal investigator). B. Slichter SJ. The threshold for prophylactic platelet transfusions in adults with acute myeloid leukemia. Carr. and University of Wisconsin–Madison.D. D. Mette. Cox DR. Blanker. M.S. et al. Enger C. Hoffman. Woodson. C.2. Whitsett. E. Background. Dr. Aboulafia. University of Oklahoma. Cox. Einarson. DuBois EF. Zeger SL. Kaufman. Dartmouth–Hitchcock Medical Center. Lane. Marangoni F. Josephson. University of North Carolina. Cancer 1981.E.L. Castillejo. Slichter reports receiving grant support from U. S. Roudot-Thoraval F. M. M. Hess (principal investigator). Chlebeck. T. Whitaker BI. St. 16. DuBois D. Platelet transfusion: a dose-response study. Shapiro. Koenig. 2010.pdf. Granger. Triulzi. et al. Spanfelner. Longitudinal data analysis using generalized linear models. Stublaski. J. Copyright © 2010 Massachusetts Medical Society.G. J Chronic Dis 1974.21:78-84. Stadtmauer. et al. 9. and lecture fees from EMD Healthcare Communications Scientific Communication Group. George (principal investigator). Terrell. Josephson. T. Milwaukee: A. A. P.B.) 17. and Blood Institute. Hedstrom. Tinmouth A. Philadelphia: B. R. MD: G. and design of a clinical trial to assess the effects of platelet dose on bleeding risk in thrombocytopenic patients. Froedert Memorial Lutheran Hospital. K. Rebulla P. Milwaukee. 8. Cruz. receiving lecture fees from Mediware.F.K. University of Pittsburgh. J. Green J. Arch Intern Med 1916.hhs.J. Hay. Milwaukee: R. K. E. McCullough (principal investigator). Watertown. Army Medical Research Acquisition Activity (Department of Defense). Roberson. Nemo (project officer). Nguyen. Hilbe JM. Crump M. Bussel (principal investigator). Pinaroc. Link.M. J. T. Leifer. Buchanan (principal investigator). 2000-2008. C. Skerrett. Transfusion 2004. University of Maryland. E. Hirata.91:1469-77. J. T.J. Mitrou. Slichter (principal investigator). Slichter SJ. receiving consulting fees from Fenwal Laboratories and CaridianBCT. Johns Hopkins University. Low-dose prophylactic platelet transfusions in recipients of an autologous peripheral blood progenitor cell transplant and patients with acute leukemia: a randomized controlled trial with a sequential Bayesian design. Staquet M. Transfusion 2006. Manno (principal investigator). Virginia Mason Medical Center. X. Transfus Med Rev 2003. Boston: L. Assmann (principal investigator). T. 20. 14. S. B. J. rationale. Blood 2009. J. Ieong. R. P. SAS/STAT software. Biometrika 1986. S. Dr.J. Murphy MF. Ness (principal investigator). J. Nevo S. Wallace. 7.46:903-11. T. M. Swan V. A formula to estimate the approximate surface area if height and weight be known. Dora. Reporting results of cancer treatment. Liang K-Y. Reitsma. Seattle: D. Children’s Hospital Medical Center. C. B.2:220-5. Fuller. Webert KE. V. A. Appendix The following investigators and staff participated in the study: Case Western Reserve University. McFarland (principal investigator). M. University of Pennsylvania.D. S. Slichter SJ. Transfus Med Rev 2004.337:1870-5. A. Heddle NM. 5. Cook RJ. Children’s Hospital Boston. Hyde C. NC: SAS Institute. Blood 1998. Lankiewicz. and Dr. Platelet transfusion prophylaxis for patients with haematological malignancies: where to now? Br J Haematol 2005. Fuller. Corbett. Swift. Baltimore: P. Petzold. Cook RJ. T. Atlanta: C. New Orleans: C. J. D’Andrea. Leissinger (principal investigator). Scott. The randomization and stratification of patients to clinical trials.M. Strauss (principal investigator).R. S. Corson. Hendrix. Turman. Brunskill S. Feldman. Oakes D. K.92:1448-53. Sig- 612 n engl j med 362. Rebulla P. A. S.-I. Cook RJ. 2. and Pall Medical. Wade. Schrock. receiving grant support from Z-Medica. J. Nathanson. Schmidt. Lung. Heddle NM. J. Aquino. J. Rowe. Madison: J. BloodCenter of Wisconsin. Duke University. J. McLeod. J.G. Fairview–University Medical Center. New England Research Institutes (Data Coordinating Center). S. M. A descriptive analysis of international transfusion practice and bleeding outcomes in patients with acute leukemia. L. J.B. T. receiving consulting fees from CaridianBCT. consulting fees from Bayer Healthcare. King MR. receiving consulting fees and grant support from Baxter Healthcare. et al. Assmann. Divgi. 12. Cleveland: K. Gerstenberger. Miller-Metcalfe. Boston: R.44: 1711-9. Blood 1998. Kruse-Jarres. Gernsheimer. Case. Norol F. London: Chapman & Hall. Ness. Dr. Analysis of survival data. R. A. . E. Adams. M. G. Minneapolis: J. D. S. MA: S. at http://www.L.47:207-14. Philadelphia: C. Stanworth SJ. Wagner. V. All rights reserved. 4.M.27:365-75. Neufeld (principal investigator). Controversy concerning platelet dose. Brambilla. Hinkle. Deyle. Raife. New York: J. References 1. D. M. A.A. University of Texas Southwestern Medical Center. Wissert. Werndli. A. Durham. Beth Israel Deaconess Medical Center. I. NH: J. Bethesda. Triulzi (principal investigator). and Ginny Knight at the Puget Sound Blood Center for administrative assistance. Newman. Weill College of Cornell University. L. D. 19. Hayes. Hillyer (principal investigator). Children’s Hospital of Wisconsin.D. Lebanon. Beekman. A randomized controlled trial comparing standard. Malynn. 6. Luke’s Medical Center. Boston: E. Brecher. 2010 . Lusher. Devlin. ISBT Sci Ser 2007. J. Boca Raton. Sigouin C. We thank all the patients who volunteered to take part in this study. C. Dallas: G. Seattle: D. Telen. Uhl. 13. E.113: 1564-73. Heldke. Brecher (principal investigator). (Accessed January 25. Kelly. Exum. S. B.18:153-67. Mondoro. E. Brigham and Women’s Hospital.nejm.The n e w e ng l a n d j o u r na l of m e dic i n e Dr. Johnson. Puget Sound Blood Center and University of Washington Medical Center. Tsui. Milwaukee: M. Paranjape. J Clin Apher 2006. all the study investigators and committee members. Graminske. Higgins.and low-dose strategies for transfusion of platelets (SToP) to patients with thrombocytopenia. Hardin JW. receiving consulting fees and grant support from Amgen. Generalized estimating equations. Heddle NM. M. Miller. Li.17:181-93. Braun.N. E. Hoogstraten B. Glynn. Baltimore: J. 2003. version 9.org february 18. N.A. 2010 Downloaded from www.S. C. Winkler A. N Engl J Med 1997. Geyer. Acute bleeding after bone marrow transplantation (BMT) — incidence and effect on survival: a quantitative analysis in 1. Navigant Biotechnologies. Miller. Malcolm. NC: T. Relationship between platelet count and bleeding risk in thrombocytopenic patients. 15. The 2007 National Blood Collection and Utilization Survey report. Children’s Hospital of Philadelphia. McCrae (principal investigator). Bieling P. S. Freedman J. 18.S. Manno. T. Murphy M. S. Harvath. J. Kang. J. Ortel (principal investigator). Tarng. Ruys. R. Erickson. Pittsburgh: D. A.R. National Heart.7 nejm. Punzalan. Tinmouth AT. 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39:674-81. randomized. . Hersh JK. Beginning 6 months after publication.7 nejm. full text of all journal articles on the world wide web Access to the complete contents of the Journal on the Internet is free to all subscribers. Wandt H. Features include a library of all issues since January 1993 and abstracts since January 1975. Therapeutic efficacy and safety of platelets treated with a photochemical process for pathogen inactivation: the SPRINT trial. 23. subscribers should go to the Journal’s home page (NEJM. Schaefer-Eckart K. 24. All articles can be printed in a format that is virtually identical to that of the typeset pages. Giraudeau B. 2010 . Brecher ME. the full text of all Original Articles and Special Articles is available free to nonsubscribers. All rights reserved. open. Herman JH.105: 862-4. Sensebé L. Methodologic issues in the use of bleeding as an outcome in transfusion medicine studies. Benjamin RJ.dose of Prophylactic Platelet Tr ansfusions ouin C. Frank M. Blood 2005. Kuter DJ. Transfusion 1999. Klumpp TR. Transfusion 1998. and a personal archive for saving articles and search results of interest. double-blind trial. Hom EG. Bardiaux L.org on July 14. Transfusion 2003. 21. et al. The efficiency of transfusing high doses of platelets in hematologic patients with thrombocytopenia: results of a prospective. Copyright © 2010 Massachusetts Medical Society. Blood 2004. After this one-time registration. abstract. Clinical consequences of alterations in platelet transfusion dose: a prospective. Rebulla P. Blood 2005. blinded end point (PROBE) study. et al.98:1346-51. 22. 2010 613 Downloaded from www. Mathematical modeling of platelet survival with implications for optimal transfusion practice in the chronically platelet transfusion-dependent patient.104:1534-41. Goodnough LT. Vesole DH. 25. n engl j med 362. 27. a full-text search capacity. et al.43:742-52. Brecher ME. McCullough J. Prophylactic platelet transfusions from healthy apheresis platelet donors undergoing treatment with thrombopoietin.nejm. Routine prophylactic platelet transfusions are not necessary in patients with acute myeloid leukemia — a therapeutic transfusion strategy is safe and cost effective. Hom EG. Transfusion 1999. To use this Web site. 26. subscribers can use their passwords to log on for electronic access to the entire Journal from any computer that is connected to the Internet. McCullough J.org) and register by entering their names and subscriber numbers as they appear on their mailing labels. Blood 2001.org february 18. Wilhelm M.39: 431-4. Optimal platelet dosing.38:637-44. randomized.106:129a. Gaughan JP. et al. Hersh JK. Copyright © 2010 Massachusetts Medical Society.

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