Transfusion最新文献

Background: Traumatic brain injury (TBI) carries significant mortality and morbidity in civilian and military populations. Current treatment guidelines for TBI are primarily supportive, and no pharmacological agent exists to attenuate the progression of brain injury. Valproic Acid (VPA) has long been used to treat neurological disorders; however, recent work has demonstrated its potential as a neuroprotective agent. We have already demonstrated that VPA administration in swine models of TBI (with or without associated hemorrhage and polytrauma) significantly improves survival and neurological recovery and decreases brain lesion size compared to controls. This paper introduces a phase 2/3 clinical trial that is designed to evaluate the efficacy and safety of VPA administration in patients with TBI.

Methods: In this randomized, double-blind, placebo-controlled, multicenter trial, patients with moderate to severe TBI (GCS 3-12) across nine level 1 trauma centers in the US will be randomized to receive either standard of care treatment and 250 mL of isotonic saline (control), or standard of care treatment and intravenous VPA at either 50 mg/kg (low-dose VPA group), or 100 mg/kg (high-dose VPA group). The primary endpoint of this clinical trial will be neurological status as measured by the Extended Glasgow Outcome Scale (GOS-E) 3 months post-TBI.

Discussion: Our team has conducted multiple large animal studies that strongly support the cytoprotective effects of VPA treatment. The goal of this upcoming trial is to study the efficacy and safety of two doses of VPA in patients with moderate to severe TBI.

Trial registration: ClinicalTrials.gov, https://clinicaltrials.gov/study/NCT07166393, September 3, 2025.

Background: Liberal platelet transfusion practices increase neonatal morbidity and mortality. The mechanisms underlying this harm are unknown but may involve the immune rather than hemostatic functions of platelets, as well as the significant differences between adult (transfused) and neonatal platelets, particularly the higher P-selectin surface expression on activated adult platelets. In this study, we investigated the immune/inflammatory effects of transfusing adult platelets into newborn mice.

Study design and methods: Washed platelets from wild-type (WT) or P-selectin^-/- adult donors or Tyrode's buffer control were transfused into WT and thrombocytopenic c-MPL^-/- pups. Blood was collected 2- or 4-h post-transfusion to measure a panel of plasma inflammatory cytokines, neutrophil extracellular trap (NET) formation, and the percentage of circulating platelet-monocyte and platelet-neutrophil aggregates (PMAs and PNAs).

Results: Transfusion of adult WT platelets into post-natal Day 10 (P10) and 5 (P5) WT pups increased plasma concentrations of inflammatory cytokines 2- and 4-h post-transfusion, including interleukin-6 (IL-6) and Keratinocyte-derived chemokine (KC). Transfusion of WT platelets into P10 thrombocytopenic c-MPL^-/- pups similarly increased plasma inflammatory cytokines, PMA and PNA percentages, and NET formation. Compared to WT platelets, P-selectin^-/- platelets induced similar elevations in plasma cytokines, but NET formation was attenuated and PMA and PNA percentages were comparable to those of sham-transfused pups.

Discussion: In a murine model of neonatal thrombocytopenia, transfusion of adult platelets increased PMA and PNA percentages, plasma inflammatory cytokines, and NET formation through both P-selectin-dependent and -independent mechanisms. These effects may contribute to the negative outcomes seen with liberal neonatal platelet transfusion practices.

Background: Alloimmunization against D-antigen can cause severe Hemolytic Disease of the Fetus and Newborn (HDFN). Traditionally, anti-D-titers are measured using a saline indirect antiglobulin test (tube testing). Anti-D-titers ≥8 during pregnancy trigger an escalation in maternal care. Tube testing is labor-intensive and known for imprecision. Automated gel-based titration is more sensitive and precise than tube titration for the detection of anti-D. A gel titer correlated with potential fetal anemia has not been established, as studies comparing gel and tube titers provide widely variable results. This multicenter study tested anti-D samples in parallel to characterize the difference in sensitivity between tube and automated gel assays.

Study design and methods: Patients alloimmunized to RhD had samples tested using tube and automated gel titration methods. A total of 647 samples were tested in parallel. A subset of 141 samples also had anti-D levels quantified using continuous flow analysis (CFA). Controlled lots of R₂R₂ red blood cells and standardized reagents were utilized.

Results: Results demonstrated that gel-based methods yielded mean titers 2.5-3 dilutions higher than tube; this difference diminished at tube titers >128. Notably, several samples previously considered negative by tube were positive by gel. Anti-D levels quantified by CFA demonstrated a good correlation with tube and gel testing (R = 0.75-0.9 for tube; R = 0.85-0.89 for gel).

Discussion: A tube titer of 8 to 16 correlates with an automated gel titer of 32-128 when R₂R₂ cells are used. Results using the CFA method correlate well with tube and gel analyses.

Background: Red blood cell (RBC) transfusion causes RBC alloimmunization in a st of patients. Factors that influence RBC alloimmunization risk are incompletely understood.

Study design and methods: We performed a matched case-control study of male intensive care unit (ICU) patients who did or did not develop a new RBC alloantibody after RBC transfusion. Demographic, clinical, and laboratory data were collected. Cases and controls were matched 1:2 on serological follow-up time (SFT) and the number of RBC units transfused. Conditional logistic regression analyses were performed to identify variables associated with the development of a new RBC alloantibody.

Results: One hundred and seventeen cases who developed a new RBC alloantibody during the SFT were matched with 234 controls who did not develop an alloantibody. The median SFT was 40 days among cases and 52 days among controls. The median number of RBC units transfused during the SFT was 7 in both groups. Although the total number of RBC units transfused was similar, cases were transfused RBC units in fewer transfusion episodes compared with controls. The median number of transfusion episodes, defined as a minimum time interval of 24 h between RBC transfusions, was higher in controls compared to cases. In multivariable analysis, each additional transfusion episode was associated with a 26% lower risk of RBC alloimmunization (odds ratio 0.74; 95% confidence interval 0.63-0.86; p < 0.001).

Conclusions: In a matched case-control study of male ICU patients who received a similar number of RBC transfusions, a greater number of transfusion episodes was associated with a decreased risk of developing a new RBC alloantibody.