BACKGROUND-We conducted a trial of prophylactic platelet transfusions to evaluate the effect of platelet dose on bleeding in patients with hypoproliferative thrombocytopenia.
We report a transfusion trial of platelets photochemically treated for pathogen inactivation using the synthetic psoralen amotosalen HCl. Patients with thrombocytopenia were randomly assigned to receive either photochemically treated (PCT) or conventional (control) platelets for up to 28 days. The primary end point was the proportion of patients with World Health Organization (WHO) grade 2 bleeding during the period of platelet support. A total of 645 patients (318 PCT and 327 control) were evaluated. The primary end point, the incidence of grade 2 bleeding (58.5% PCT versus 57.5% control), and the secondary end point, the incidence of grade 3 or 4 bleeding (4.1% PCT versus 6.1% control), were equivalent between the 2 groups (P ؍ .001 by noninferiority). The
Although both transfusion programs were well tolerated, our finding of more frequent major adverse neurologic events in the restrictive RBC-transfusion group suggests that the practice of restrictive transfusions may be harmful to preterm infants.
Hydroxyethyl starch (HES) is one of the most frequently used plasma substitutes. A variety of different HES solutions exist worldwide, which differ greatly in their pharmacological properties. HES is classified according to its manufactured or in vitro molecular weight (MW) into high MW (450-480 kDa), medium MW (200 kDa), and low MW (70 kDa) starch preparations. However, this is not sufficient, because as HES is metabolized in vivo, its MW changes, and it is the in vivo MW which is responsible for the therapeutic and adverse effects of each HES. The rate of metabolization depends mainly on the degree of hydroxyethyl substitution (ranging from 0.4 to 0.7), and the C2/C6 ratio of hydroxyethylation. A high degree of substitution and a high C2/C6 ratio lead to a slow metabolization of HES, resulting in a large in vivo MW. Slowly degradable high MW HES 450/0.7 and medium MW HES 200/0.62 have a high in vivo MW and are eliminated slowly via the kidneys. As a result, these starches have a relatively long-lasting volume effect. When infusing higher volumes (>1500 ml) are infused, large molecules accumulate in the plasma. This can result in bleeding complications due to decreased factor VIII/von Willebrand factor, platelet function defects, incorporation into fibrin clots, and an unfavorable effect on rheological parameters. Rapidly degradable medium MW HES 200/0.5 or low MW HES 70/0.5 are quickly split in vivo into smaller, more favorable molecule sizes, resulting in faster renal elimination, shorter volume effect, and fewer adverse effects on coagulation and rheological parameters. For historical and marketing reasons, only slowly degradable, high MW HES (480/0.7) is available in the United States. In Europe, a large variety of HES solutions are available, dominated by medium MW, easily degradable HES (200/0.5). Because of increasing international competition and the availability of newly developed starches, it is important to be aware of the pharmacological properties of HES and the advantages and disadvantages of the individual preparations.
Giving prophylactic platelets at a threshold of < or = 10,000/microL compared with < or = 20,000/microL can decrease the total utilization of platelets with only a small adverse effect on bleeding, and no statistically significant effect on morbidity.
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