The aim of this study was to assess the survival impact of low-titer group O whole blood (LTOWB) in injured pediatric patients who require massive transfusion.
Limited data are available regarding ...the effectiveness of LTOWB in pediatric trauma.
A prospective observational study of children requiring massive transfusion after injury at UPMC Children's Hospital of Pittsburgh, an urban academic pediatric Level 1 trauma center. Injured children ages 1 to 17 years who received a total of >40 mL/kg of LTOWB and/or conventional components over the 24 hours after admission were included. Patient characteristics, blood product utilization and clinical outcomes were analyzed using Kaplan-Meier survival curves, log rank tests and Cox proportional hazards regression analyses. The primary outcome was 28-day survival.
Of patients analyzed, 27 of 80 (33%) received LTOWB as part of their hemostatic resuscitation. The LTOWB group was comparable to the component therapy group on baseline demographic and physiologic parameters except older age, higher body weight, and lower red blood cell and plasma transfusion volumes. After adjusting for age, total blood product volume transfused in 24 hours, admission base deficit, international normalized ratio (INR), and injury severity score (ISS), children who received LTOWB as part of their resuscitation had significantly improved survival at both 72 hours and 28 days post-trauma adjusted odds ratio (AOR) 0.23, P = 0.009 and AOR 0.41, P = 0.02, respectively; 6-hour survival was not statistically significant (AOR = 0.51, P = 0.30). Survivors at 28 days in the LTOWB group had reduced hospital LOS, ICU LOS, and ventilator days compared to the CT group.
Administration of LTOWB during the hemostatic resuscitation of injured children requiring massive transfusion was independently associated with improved 72-hour and 28-day survival.
In a randomized trial involving patients who were hypotensive after trauma, 30-day mortality was 33% among patients who received standard crystalloid-based resuscitation as compared with 23% among ...patients who received fresh frozen plasma in addition to standard measures.
The hypercoagulable state associated with pancreatic adenocarcinoma (PDA) results in increased risk of venous thromboembolism, leading to substantial morbidity and mortality. Recently, neutrophil ...extracellular traps (NETs), whereby activated neutrophils release their intracellular contents containing DNA, histones, tissue factor, high mobility group box 1 (HMGB1) and other components have been implicated in PDA and in cancer-associated thrombosis.
Utilizing an orthotopic murine PDA model in C57/Bl6 mice and patient correlative samples, we studied the role of NETs in PDA hypercoagulability and targeted this pathway through treatment with the NET inhibitor chloroquine. PAD4 and RAGE knockout mice, deficient in NET formation, were used to study the role of NETs in platelet aggregation, release of tissue factor and hypercoagulability. Platelet aggregation was assessed using collagen-activated impedance aggregometry. Levels of circulating tissue factor, the initiator of extrinsic coagulation, were measured using ELISA. Thromboelastograms (TEGs) were performed to assess hypercoagulability and changes associated with treatment. Correlative data and samples from a randomized clinical trial of preoperative gemcitabine/nab-paclitaxel with and without hydroxychloroquine were studied and the impact of treatment on venous thromboembolism (VTE) rate was evaluated.
The addition of NETs to whole blood stimulated platelet activation and aggregation. DNA and the receptor for advanced glycation end products (RAGE) were necessary for induction of NET associated platelet aggregation. PAD4 knockout tumor-burdened mice, unable to form NETs, had decreased aggregation and decreased circulating tissue factor. The NET inhibitor chloroquine reduces platelet aggregation, reduces circulating tissue factor and decreases hypercoagulability on TEG. Review of correlative data from patients treated on a randomized protocol of preoperative chemotherapy with and without hydroxychloroquine demonstrated a reduction in peri-operative VTE rate from 30 to 9.1% with hydroxychloroquine that neared statistical significance (p = 0.053) despite the trial not being designed to study VTE.
NETs promote hypercoagulability in murine PDA through stimulation of platelets and release of tissue factor. Chloroquine inhibits NETs and diminishes hypercoagulability. These findings support clinical study of chloroquine to lower rates of venous thromboembolism in patients with cancer.
This study reports correlative data from two clinical trials that registered with clinicaltrials.gov, NCT01128296 (May 21, 2010) and NCT01978184 (November 7, 2013).
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The transfusion of cold-stored uncrossmatched whole blood (WB) has not been extensively used in civilian trauma resuscitation. This report details the initial experience with the safety and ...feasibility of using WB in this setting after a change of practice at a Level 1 trauma center was instituted.
Up to two units of uncrossmatched group O positive WB that was leukoreduced using a platelet-sparing filter from male donors were transfused to male trauma patients with hypotension secondary to bleeding. Hemolytic marker haptoglobin and reports of transfusion reactions in these patients were followed. Additionally, transfusion volumes and outcomes were compared to a historical cohort of male trauma patients who received at least one red blood cell (RBC) unit, but not WB, during the first 24 hours of admission.
There were 47 WB patients who were transfused with a mean (SD) of 1.74 (0.61) WB units. The median haptoglobin concentration on post-WB transfusion Day 1 was 25.1 (9.3) mg/dL in 7 of 30 non-group O recipients. No adverse reactions in temporal relation to the WB transfusions were reported. There were 145 male historical control patients identified who were resuscitated with component therapy; the median volume of incompatible plasma transfused to the WB versus component therapy group was not significantly different (1,000 vs. 800 mL, respectively; p = 0.38); the mean plasma:RBC (0.99 0.47 vs. 0.77 0.73, respectively; p = 0.006) and platelet:RBC (0.72 0.40 vs. 0.51 0.734, respectively; p < 0.0001) ratios were significantly higher in the WB group.
Transfusion of two units of cold-stored uncrossmatched WB is feasible and seems to be safe in civilian trauma resuscitation. Determining the efficacy of WB with regard to reducing the number of blood products transfused in the first 24 hours or improving recipient survival will require a larger randomized trial.
Therapeutic study, level IV.
Background
The serological safety of transfusing low titer group O whole blood (LTOWB) with an anti‐A and anti‐B titer of <100 was evaluated in group O and non‐group O trauma recipients.
Methods
...Civilian adult trauma patients who received ≥4 units of leukoreduced LTOWB during their initial resuscitation and who survived for >24 h after admission at two level 1 trauma centers were included in this retrospective study. Lactate dehydrogenase (LDH), total bilirubin, haptoglobin, potassium, creatinine were evaluated on the day of LTOWB transfusion (day 0) and on the next 3 days.
Results
There were 77 injured recipients evaluated: 39 non‐group O and 38 group O. The median (IQR) number of transfused LTOWB units was 4 (4–6) and 4 (4–5), respectively, and the maximum number of units was 8 and 11, respectively. The non‐group O patients received a median (IQR) volume of 1710 ml (1368–2070) of ABO‐incompatible plasma. Comparing non‐group O to group O recipients, there were no significant differences in the median haptoglobin, LDH, or creatinine concentrations at any time point. The median concentration of total bilirubin was significantly higher amongst the non‐group O recipients on days 1 and 2, while on day 0 the median potassium concentration was significantly higher amongst the group O recipients. All median elevated values were within the laboratory's normal range. Amongst the non‐group O recipients there were no reported transfusion reactions.
Conclusion
Receiving at least four LTOWB units (anti‐A&B titer <100) was not associated with biochemical/clinical evidence of hemolysis in adult trauma patients.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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