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Age-group analyses were conducted of patients in the prophylactic platelet dose trial (PLADO), which evaluated the relation between platelet dose per transfusion and bleeding. Hospitalized patients with treatment-induced hypoproliferative thrombocytopenia were randomly assigned to 1 of 3 platelet doses: 1.1 × 10(11), 2.2 × 10(11), or 4.4 × 10(11) platelets/m(2) per transfusion, given for morning counts of ≤ 10 000 platelets/μL. Daily hemostatic assessments were performed. The primary end point (percentage of patients who developed grade 2 or higher World Health Organization bleeding) was evaluated in 198 children (0-18 years) and 1044 adults. Although platelet dose did not predict bleeding for any age group, children overall had a significantly higher risk of grade 2 or higher bleeding than adults (86%, 88%, 77% vs 67% of patients aged 0-5 years, 6-12 years, 13-18 years, vs adults, respectively) and more days with grade 2 or higher bleeding (median, 3 days in each pediatric group vs 1 day in adults; P < .001). The effect of age on bleeding differed by disease treatment category and was most pronounced among autologous transplant recipients. Pediatric subjects were at higher risk of bleeding over a wide range of platelet counts, indicating that their excess bleeding risk may be because of factors other than platelet counts.

Platelet characteristics, such as platelet dose, platelet source (apheresis vs pooled), platelet donor-recipient ABO compatibility, and duration of platelet storage, can affect posttransfusion platelet increments, but it is unclear whether these factors impact platelet transfusion efficacy on clinical bleeding. We performed secondary analyses of platelet transfusions given in the prospective randomized Platelet Dose Study, which included 1272 platelet-transfused hematology-oncology patients who received 6031 prophylactic platelet transfusions. The primary outcome of these analyses was time from first transfusion to first World Health Organization ≥ grade 2 bleeding. Platelet transfusion increments were assessed at 0.25 to 4 hours and 16 to 32 hours after platelet transfusion. There were 778 patients evaluable for analysis of time to bleeding. Adjusted models showed that randomized dose strategy, platelet source, ABO compatibility, and duration of storage did not predict this outcome. Platelet increments were generally higher for transfusions of apheresis platelets, ABO-identical platelets, and platelets stored 3 days versus 4 to 5 days. Thus, although platelet source, ABO compatibility, and duration of storage exert a modest impact on both absolute and corrected posttransfusion platelet increments, they have no measurable impact on prevention of clinical bleeding. This trial was registered at www.clinicaltrials.gov as #NCT00128713.

The Stroke Prevention Trial in Sickle Cell Anemia (STOP) was a randomized trial to evaluate whether chronic transfusion could prevent initial stroke in children with sickle-cell anemia at high risk as determined by transcranial Doppler (TCD). The trial demonstrated a large benefit of transfusion and was halted early. After termination of the trial, patients participated in a post-trial follow-up study. More patients in the transfusion group (70%) elected transfusion for primary stroke prevention compared with those on standard care (45%). Six patients with persistently abnormal TCD results developed stroke. A minority with initially abnormal TCD results remained stroke-free without transfusion. Except for lower baseline and follow-up TCD velocities compared with those with stroke, no predictive features of this apparent lower-risk subgroup could be determined. TCD results at last testing in 108 patients that did not have stroke were: normal (44.4%), conditional (26.9%), abnormal (22.2%), and inadequate (6.5%). Patients on transfusion were more likely to have normal TCD results. Transfusion resulted in iron overload and alloimmunization, but no infection. The study provides new information on acceptance rates and long-term effects of transfusion. Persistent TCD elevation signals ongoing stroke risk. Reduction in TCD results over time without transfusion is observed in some patients and requires further study.

The Stroke Prevention Trial in Sickle Cell Anemia (STOP) was a randomized multicenter controlled trial comparing prophylactic blood transfusion with standard care in sickle cell anemia (SCA) children aged 2 to 16 years selected for high stroke risk by transcranial Doppler (TCD). More than 2000 children were screened with TCD to identify the 130 high-risk children who entered the randomized trial. A total of 5613 TCD studies from 2324 children were evaluated. We also collected information on stroke. We describe the changes in TCD with repeated testing and report the outcome without transfusion in the STOP screened cohort. Risk of stroke was higher with abnormal TCD than with normal or conditional TCD (P <.001) or inadequate TCD (P =.002), and risk with conditional TCD was higher than with normal TCD (P <.001). Repeated TCD in 1215 children showed that the condition of 9.4% of children became abnormal during observation. Younger patients and those with higher initial flow velocities were most likely to convert to abnormal TCDs. Screening in STOP confirmed the predictive value of TCD for stroke. Substantial differences in the probability of conversion to abnormal TCD were observed, with younger children and those with higher velocity more likely to have an abnormal TCD with rescreening.

The stroke prevention study in sickle cell disease (STOP) demonstrated a 90% reduction in stroke risk with transfusion among patients with time-averaged mean cerebral blood velocity (TAMV) of 200 cm/s or more as measured by transcranial Doppler (TCD). In STOP, 232 brain magnetic resonance angiograms (MRAs) were performed on 100 patients, 47 in the transfusion arm and 53 in the standard care arm. Baseline MRA findings were interpreted as normal in 75 patients and as indicating mild stenosis in 4 patients and severe stenosis in 21 patients. Among 35 patients who underwent magnetic resonance angiography within 30 days of random assignment, the TAMV was significantly higher in 7 patients with severe stenosis compared with 28 patients with normal MRA findings or mild stenosis (276.7 +/- 34 vs 215 +/- 15.6 cm/s; P<.001). In the standard care arm, 4 of 13 patients with abnormal MRA findings had strokes compared with 5 of 40 patients with normal MRA findings (P=.03). In this arm, TAMV became normal (less than 170 cm/s) or conditional (170-199 cm/s) in 26 of 38 patients with normal or mildly abnormal baseline MRA but remained abnormal in 8 of 10 patients with severely abnormal baseline MRA. These results suggest that TCD often detects flow abnormalities indicative of stroke risk before MRA lesions become evident. Furthermore, patients with abnormal MRA findings and higher TCD velocities are at higher risk for stroke, and their cerebral TAMVs are unlikely to decrease without transfusion.