To determine the effect of blood component ratios in massive transfusion (MT), we hypothesized that increased use of plasma and platelet to red blood cell (RBC) ratios would result in decreased early ...hemorrhagic death and this benefit would be sustained over the ensuing hospitalization.
Civilian guidelines for massive transfusion (MT > or =10 units of RBC in 24 hours) have typically recommend a 1:3 ratio of plasma:RBC, whereas optimal platelet:RBC ratios are unknown. Conversely, military data shows that a plasma:RBC ratio approaching 1:1 improves long term outcomes in MT combat casualties. There is little consensus on optimal platelet transfusions in either civilian or military practice. At present, the optimal combinations of plasma, platelet, and RBCs for MT in civilian patients is unclear.
Records of 467 MT trauma patients transported from the scene to 16 level 1 trauma centers between July 2005 and June 2006 were reviewed. One patient who died within 30 minutes of admission was excluded. Based on high and low plasma and platelet to RBC ratios, 4 groups were analyzed.
Among 466 MT patients, survival varied by center from 41% to 74%. Mean injury severity score varied by center from 22 to 40; the average of the center means was 33. The plasma:RBC ratio ranged from 0 to 2.89 (mean +/- SD: 0.56 +/- 0.35) and the platelets:RBC ratio ranged from 0 to 2.5 (0.55 +/- 0.50). Plasma and platelet to RBC ratios and injury severity score were predictors of death at 6 hours, 24 hours, and 30 days in multivariate logistic models. Thirty-day survival was increased in patients with high plasma:RBC ratio (> or =1:2) relative to those with low plasma:RBC ratio (<1:2) (low: 40.4% vs. high: 59.6%, P < 0.01). Similarly, 30-day survival was increased in patients with high platelet:RBC ratio (> or =1:2) relative to those with low platelet:RBC ratio (<1:2) (low: 40.1% vs. high: 59.9%, P < 0.01). The combination of high plasma and high platelet to RBC ratios were associated with decreased truncal hemorrhage, increased 6-hour, 24-hour, and 30-day survival, and increased intensive care unit, ventilator, and hospital-free days (P < 0.05), with no change in multiple organ failure deaths. Statistical modeling indicated that a clinical guideline with mean plasma:RBC ratio equal to 1:1 would encompass 98% of patients within the optimal 1:2 ratio.
Current transfusion practices and survival rates of MT patients vary widely among trauma centers. Conventional MT guidelines may underestimate the optimal plasma and platelet to RBC ratios. Survival in civilian MT patients is associated with increased plasma and platelet ratios. Massive transfusion practice guidelines should aim for a 1:1:1 ratio of plasma:platelets:RBCs.
Whole Blood Transfusion Cap, Andrew P; Beckett, Andrew; Benov, Avi ...
Military medicine,
09/2018, Volume:
183, Issue:
suppl_2
Journal Article
Peer reviewed
Open access
Whole blood is the preferred product for resuscitation of severe traumatic hemorrhage. It contains all the elements of blood that are necessary for oxygen delivery and hemostasis, in nearly ...physiologic ratios and concentrations. Group O whole blood that contains low titers of anti-A and anti-B antibodies (low titer group O whole blood) can be safely transfused as a universal blood product to patients of unknown blood group, facilitating rapid treatment of exsanguinating patients. Whole blood can be stored under refrigeration for up to 35 days, during which it retains acceptable hemostatic function, though supplementation with specific blood components, coagulation factors or other adjuncts may be necessary in some patients. Fresh whole blood can be collected from pre-screened donors in a walking blood bank to provide effective resuscitation when fully tested stored whole blood or blood components are unavailable and the need for transfusion is urgent. Available clinical data suggest that whole blood is at least equivalent if not superior to component therapy in the resuscitation of life-threatening hemorrhage. Low titer group O whole blood can be considered the standard of care in resuscitation of major hemorrhage.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, VSZLJ
BACKGROUND: There is little systematically derived evidence‐based guidance to inform plasma transfusion decisions. To address this issue, the AABB commissioned the development of clinical practice ...guidelines to help direct appropriate transfusion of plasma.
STUDY DESIGN AND METHODS: A systematic review (SR) and meta‐analysis of randomized and observational studies was performed to quantify known benefits and harms of plasma transfusion in common clinical scenarios (see accompanying article). A multidisciplinary guidelines panel then used the SR and the GRADE methodology to develop evidence‐based plasma transfusion guidelines as well as identify areas for future investigation.
RESULTS: Based on evidence ranging primarily from moderate to very low in quality, the panel developed the following guidelines: 1) The panel suggested that plasma be transfused to patients requiring massive transfusion. However, 2) the panel could not recommend for or against transfusion of plasma at a plasma : red blood cell ratio of 1:3 or more during massive transfusion, 3) nor could the panel recommend for or against transfusion of plasma to patients undergoing surgery in the absence of massive transfusion. 4) The panel suggested that plasma be transfused in patients with warfarin therapy–related intracranial hemorrhage, 5) but could not recommend for or against transfusion of plasma to reverse warfarin anticoagulation in patients without intracranial hemorrhage. 6) The panel suggested against plasma transfusion for other selected groups of patients.
CONCLUSION: We have systematically developed evidence‐based guidance to inform plasma transfusion decisions in common clinical scenarios. Data from additional randomized studies will be required to establish more comprehensive and definitive guidelines for plasma transfusion.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Hemostatic resuscitation using blood components in a 1:1:1 ratio of platelets:fresh frozen plasma:red blood cells (RBCs) is based on analyses of massive transfusion (MT, ≥10 RBC units in 24 hours). ...These 24-hour analyses are weakened by survival bias and do not describe the timing and location of transfusions. Mortality outcomes associated with early (first 6 hours) resuscitation incorporating platelets, for combat casualties requiring MT, have not been reported.
We analyzed records for 8,618 casualties treated at the United States military hospital in Baghdad, Iraq, between January 2004 and December 2006. Patients (n = 414) requiring MT, not receiving fresh whole blood, and surviving at least 1 hour (reducing survival bias) were divided into 6-hour apheresis platelet (aPLT) transfusion ratio groups: LOW (aPLT:RBC, ≤0.1, n = 344) and HIGH (aPLT:RBC, >0.1, n = 70). Baseline characteristics of groups were compared. Factors influencing survival on univariate analysis were included in Cox proportional hazards models of 24-hour and 30-day survival.
Patients received aPLT in the emergency department (4%), operating room (45%), intensive care unit (51%). The HIGH group presented with higher (p < 0.05) admission International Normalized Ratio (1.6 vs. 1.4), base deficit (8 vs. 7), and temperature (36.7 vs. 36.4). Overall mortality was 27%. At 24 hours, the HIGH group showed lower mortality (10.0% vs. 22.1%, p = 0.02). Absolute differences in 30-day mortality were not significant (HIGH, 18.6%; LOW, 28.8%, p = 0.08). On adjusted analysis, the HIGH group was independently associated with increased survival: LOW group mortality hazard ratios were 4.1 at 24 hours and 2.3 at 30 days compared with HIGH group (p = 0.03 for both). Increasing 6-hour FFP:RBC ratio was also independently associated with increased survival.
Early (first 6 hours) hemostatic resuscitation incorporating platelets and plasma is associated with improved 24-hour and 30-day survival in combat casualties requiring MT.
Synthetic supramolecular zipper complexes have been used to quantify substituent effects on the free energies of aromatic stacking interactions. The conformational properties of the complexes have ...been characterised using NMR spectroscopy in CDCl(3), and by comparison with the solid state structures of model compounds. The structural similarity of the complexes makes it possible to apply the double mutant cycle method to evaluate the magnitudes of 24 different aromatic stacking interactions. The major trends in the interaction energy can be rationalised using a simple model based on electrostatic interactions between the pi-faces of the two aromatic rings. However, electrostatic interactions between the substituents of one ring and the pi-face of the other make an additional contribution, due to the slight offset in the stacking geometry. This property makes aromatic stacking interactions particularly sensitive to changes in orientation as well as the nature and location of substituents.
BACKGROUND: At major combat hospitals, the military is able to provide blood products to include apheresis platelets (aPLT), but also has extensive experience using fresh whole blood (FWB). In ...massively transfused trauma patients, we compared outcomes of patients receiving FWB to those receiving aPLT.
STUDY DESIGN AND METHODS: This study was a retrospective review of casualties at the military hospital in Baghdad, Iraq, between January 2004 and December 2006. Patients requiring massive transfusion (≥10 units in 24 hr) were divided into two groups: those receiving FWB (n = 85) or aPLT (n = 284) during their resuscitation. Admission characteristics, resuscitation, and survival were compared between groups. Multivariate regression analyses were performed comparing survival of patients at 24 hours and at 30 days. Secondary outcomes including adverse events and causes of death were analyzed.
RESULTS: Unadjusted survival between groups receiving aPLT and FWB was similar at 24 hours (84% vs. 81%, respectively; p = 0.52) and at 30 days (60% versus 57%, respectively; p = 0.72). Multivariate regression failed to identify differences in survival between patients receiving PLT transfusions either as FWB or as aPLT at 24 hours or at 30 days.
CONCLUSIONS: Survival for massively transfused trauma patients receiving FWB appears to be similar to patients resuscitated with aPLT. Prospective trials will be necessary before consideration of FWB in the routine management of civilian trauma. However, in austere environments where standard blood products are unavailable, FWB is a feasible alternative.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Purpose
Breast tumors from young women under the age of 40 account for approximately 7% of cases and have a poor prognosis independent of established prognostic factors. We evaluated the patient ...population served by the Military Health System, where a disproportionate number of breast cancer cases in young women are seen and treated in a single universal coverage healthcare system.
Methods
The Military Health System Repository and the DoD Central Registration databases were used to identify female breast cancer patients diagnosed or treated at military treatment facilities from 1998 to 2007.
Results
10,066 women were diagnosed with invasive breast cancer at DoD facilities from 1998 to 2007, of which 11.3% (1139), 23.4% (2355) and 65.2% (6572) were < 40, 40–49 and > 50 years old (yo), respectively, at diagnosis. 53% in the < 40 yo cohort were white, 25% were African American (AA) and 8% were Hispanic, with 14% undisclosed. Breast cancer in women diagnosed < 40 yo was more high grade (
p
< 0.0001), Stage II (
p
< 0.0001) and ER negative (
p
< 0.0001). There was a higher rate of bilateral mastectomies among the women < 40 compared to those 40–49 and > 50 (18.4% vs. 9.1% and 5.0%, respectively). Independent of disease stage, chemotherapy was given more frequently to < 40 yo (90.43%) and 40–49 yo (81.44%) than ≥ 50 yo (53.71%). The 10-year overall survival of younger women was similar to the ≥ 50 yo cohort. Outcomes in the African American and Hispanic subpopulations were comparable to the overall cohort.
Conclusion
Younger women had a similar overall survival rate to older women despite receiving more aggressive treatment.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The chief goal of the Blood Profiling Atlas in Cancer (BloodPAC) consortium is to promote collaborative efforts that support the development and implementation of liquid biopsy tests. Here, we report ...the results of a pilot study conducted by three BloodPAC members that aimed to demonstrate a multisite liquid biopsy testing framework using longitudinal blood specimens from 38 patients with metastatic breast cancer. Three laboratories receiving identical samples from two clinical sites each applied a different targeted sequencing platform to analyze mutations in cell-free DNA (cfDNA). The resulting mutational profiles reflected common breast cancer alterations, including clinically actionable mutations for 40% of hormone- receptor-positive patients. In 12 genes with shared target regions across sequencing panels, perfect inter-assay concordance was also observed for mutations detected above the lowest common assay limit of detection. Whole-genome copy number profiling of cfDNA and circulating tumor cells (CTCs) further revealed marked heterogeneity in copy number alterations and cfDNA tumor fractions across patients. Additionally, comparison of tumor fraction and CTC abundance demonstrated the complementary nature of cfDNA and CTC analyses. Overall, the framework described in this study may serve as a resource for future trials aiming to identify multimodal liquid biopsy biomarkers to guide clinical care.
Ebola virus is a highly lethal human pathogen and is rapidly driving many wild primate populations toward extinction. Several lines of evidence suggest that innate, nonspecific host factors are ...potentially critical for survival after Ebola virus infection. Here, we show that nonreplicating Ebola virus-like particles (VLPs), containing the glycoprotein (GP) and matrix protein virus protein (VP)40, administered 1-3 d before Ebola virus infection rapidly induced protective immunity. VLP injection enhanced the numbers of natural killer (NK) cells in lymphoid tissues. In contrast to live Ebola virus, VLP treatment of NK cells enhanced cytokine secretion and cytolytic activity against NK-sensitive targets. Unlike wild-type mice, treatment of NK-deficient or -depleted mice with VLPs had no protective effect against Ebola virus infection and NK cells treated with VLPs protected against Ebola virus infection when adoptively transferred to naive mice. The mechanism of NK cell-mediated protection clearly depended on perforin, but not interferon-gamma secretion. Particles containing only VP40 were sufficient to induce NK cell responses and provide protection from infection in the absence of the viral GP. These findings revealed a decisive role for NK cells during lethal Ebola virus infection. This work should open new doors for better understanding of Ebola virus pathogenesis and direct the development of immunotherapeutics, which target the innate immune system, for treatment of Ebola virus infection.
OBJECTIVE:Fresh whole blood (FWB) and red blood cells (RBCs) are transfused to injured casualties in combat support hospitals. We evaluated the risks of FWB and RBCs transfused to combat-related ...casualties.
DESIGN:Retrospective chart review.
SETTING:Deployed U.S. Army combat support hospitals.
SUBJECTS:Donors of FWB and recipients of FWB and RBCs.
MEASUREMENTS AND RESULTS:The storage age of RBCs at transfusion was measured as an indicator of overall risk associated with the storage lesion of RBCs between January 2004 and December 2004 at one combat support hospital. Between April 2004 and December 2004, FWB was prescreened only at one combat support hospital for human immunodeficiency virus, hepatitis C virus, and hepatitis B surface antigen before transfusion. To estimate the general incidence of infectious agent contamination in FWB units, samples collected between May 2003 and February 2006 were tested retrospectively for human immunodeficiency virus, hepatitis B surface antigen, hepatitis C virus, and human lymphotropic virus. Results were compared between FWB samples prescreened and not prescreened for infectious agents before transfusion. At one combat support hospital in 2004, 87 patients were transfused 545 units of FWB and 685 patients were transfused 5,294 units of RBCs with a mean age at transfusion of 33 days (±6 days). Retrospective testing of 2,831 samples from FWB donor units transfused in Iraq and Afghanistan between May 2003 and February 2006 indicated that three of 2,831 (0.11%) were positive for hepatitis C virus recombinant immunoblot assay, two of 2,831 (0.07%) were positive for human lymphotropic virus enzyme immunoassay, and none of 2,831 were positive for both human immunodeficiency virus 1/2 and hepatitis B surface antigen by Western blot and neutralization methods, respectively. The differences in the incidence of hepatitis C virus contamination of FWB donor units between those prescreened for hepatitis C virus (zero of 406; 0%) and not prescreened (three of 2,425; 0.12%) were not significant (p = .48).
CONCLUSIONS:The risk of infectious disease transmission with FWB transfusion can be minimized by rapid screening tests before transfusion. Because of the potential adverse outcomes of transfusing RBCs of increased storage age to combat-related trauma patients, the risks and benefits of FWB transfusions must be balanced with those of transfusing old RBCs in patients with life-threatening traumatic injuries.
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