Inhibitory neurosteroids, molecules generated in glia from circulating steroid hormones and de novo from cholesterol, keep seizures in check in epileptic animals. They can enhance inhibitory transmission mediated by gamma‐aminobutyric acid receptors and have anticonvulsant action. ANN NEUROL 2010;67:689–693
BACKGROUND Whole blood (WB) is an appealing alternative to component‐based transfusion in patients with significant bleeding. Historically, WB was transfused less than 48 hours after collection and was not leukoreduced (LR). However, LR components are now standard in many hospitals and LR WB is desirable. We investigated the effect of the type of LR filter used, as well as storage duration, on coagulation laboratory testing of WB. STUDY DESIGN AND METHODS Ten units of LR WB—5 units manufactured with a Food and Drug Administration (FDA)‐approved platelet (PLT)‐sparing filter (WB‐PS) and 5 units manufactured with an FDA‐approved non–PLT‐sparing filter (WB‐NPS)—underwent complete blood count, PLT function analyzer (PFA [PFA‐100]), thromboelastography (TEG), prothrombin time (PT), partial thromboplastin time (PTT), Factor (F)V activity, chromogenic FVIII, thrombin generation, and microparticle quantification on Storage Days 3, 5, 7, 10, and 14. RESULTS WB‐PS contains more PLTs than WB‐NPS (mean, 71 × 109/L vs. 1 × 109/L, p < 0.001). WB‐PS yielded essentially normal TEG tracings, while TEG tracings of WB‐NPS were grossly abnormal (mean reaction time, 7.0 min for WB‐PS vs. 9.7 min for WB‐NPS, p < 0.001; mean alpha‐angle 54.9° vs. 38.1°, p < 0.001; mean maximum amplitude, 54.9 mm vs. 13.9 mm, p < 0.001). PFA‐100 closure was more common among units of WB‐PS compared to units of WB‐NPS (72% vs. 4%, p < 0.001). PT, PTT, and factor activities were not dramatically affected by the LR filter. CONCLUSION The choice LR filter has a major impact on the hemostatic properties of WB. Although storage of WB is associated with a rapid decline in PLT count, hemostasis as assessed by TEG and PFA‐100 is not diminished over a 2‐week storage period.
BACKGROUND Evidence regarding the safety and efficacy of anticoagulant thromboprophylaxis among pediatric patients hospitalized for COVID-19 is limited. We sought to evaluate safety, dose-finding, and preliminary efficacy of twice-daily enoxaparin as primary thromboprophylaxis among children hospitalized for symptomatic COVID-19 including primary respiratory infection and multisystem inflammatory syndrome in children (MIS-C). METHODS We performed a phase 2, multicenter, prospective, open-label, single-arm clinical trial of twice-daily enoxaparin (initial dose: 0.5mg/kg/dose; max: 60 mg; adjusted to a target anti-Xa activity: 0.20-0.49 IU/ml) as primary thromboprophylaxis for children <18 years of age hospitalized for symptomatic COVID-19. Study endpoints included: (1) cumulative incidence of International Society of Thrombosis and Haemostasis-defined clinically relevant bleeding; (2) enoxaparin dose-requirements; and (3) cumulative incidence of venous thromboembolism within 30-days of hospital discharge. Descriptive statistics summarized endpoint estimates that were further evaluated by patient age (±12 years) and clinical presentation. RESULTS Forty children were enrolled and 38 met criteria for analyses. No participants experienced clinically relevant bleeding. Median (interquartile range) dose to achieve target anti-Xa levels was 0.5 mg/kg (0.48-0.54). Dose-requirement did not differ by age (0.5 [0.46-0.52] mg/kg for age ≥12 years versus 0.52 [0.49-0.55] mg/kg for age <12 years, P=0.51) but greater for participants with MIS-C (0.52 [0.5-0.61] mg/kg) as compared to primary COVID-19 (0.48 [0.39-0.51] mg/kg, P=0.010). Two children (5.3%) developed central-venous catheter-related venous thromboembolism. No serious adverse events were related to trial intervention, including one death. CONCLUSIONS Among children hospitalized for COVID-19, thromboprophylaxis with twice-daily enoxaparin appears safe and warrants further investigation to assess efficacy.
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