Microchimerism in transfused trauma patients is associated with diminished donor-specific lymphocyte response

BACKGROUND: Blood transfusion can result in long-term survival of donor leukocyte subpopulations, or microchimerism, in the peripheral blood of injured patients. Neither injury severity nor the number of transfusions is associated with its occurrence. We sought to determine whether changes in general or antigen-specific lymphocyte activation may be associated with the subsequent development of microchimerism. METHODS: We evaluated 63 transfused trauma patients, which we compared with 10 non-transfused trauma patients and 10 healthy control subjects. Of the 63 transfused patients, 31 were known to have evidence of microchimerism at hospital discharge with real-time quantitative PCR for non-recipient HLA DR alleles. We assessed lymphocyte response to phytohemagglutinin (PHA) using blood sampled upon arrival to the hospital (before transfusion) and at discharge. We performed one-way mixed leukocyte cultures (MLC) with pre-transfusion recipient specimens to assess recipient lymphocyte response to mitomycin-C treated donor cells and vice versa. RESULTS: Lymphocyte response to PHA in microchimeric transfusion recipients was lower at admission (before transfusion) and discharge than in non-microchimeric recipients. Lymphocytes from microchimeric patients had less response to donor cells than did lymphocytes from non-microchimeric patients. Microchimeric patients also more frequently had diminished lymphocyte response to a single blood donor on MLC. CONCLUSIONS: Transfusion-associated microchimerism is correlated with diminished response to mitogen challenge as well as to specific alloantigenic challenges. This microchimerism is predated by diminished lymphocyte response to a specific blood donor in many instances. The blood donor associated with this diminished alloantigenic lymphocyte response may be the source of microchimeric cells present in the recipient.     

The role of acute blood transfusion in the development of acute respiratory distress syndrome in patients with severe trauma

BACKGROUND: Patients with major trauma necessitating the transfusion of packed red blood cells (PRBCs) are at increased risk for the acute respiratory distress syndrome (ARDS). However, it is presently unknown whether the amount of transfused blood is independently associated with development of ARDS in patients with severe trauma. METHODS: This is a prospective cohort study of 102 consecutive patients with severe trauma from an intensive care unit in a Level I trauma center. RESULTS: Patients were divided into three predetermined groups on the basis of the total number of units of PRBCs received in the initial 24 hours. A significant association was identified between an acute exposure to transfused blood and the development of ARDS. Twenty-one percent of patients who received 0 to 5 units of PRBCs developed ARDS, compared with 31% of those patients who received 6 to 10 units of PRBCs and 57% of those who received greater than 10 units of PRBCs (p = 0.007). The association between the amount of transfused blood and the development of ARDS remained significant in a multivariable logistic regression model accounting for differences in severity of illness, type of trauma, race, gender, and base deficit (p = 0.002; odds ratio, 14.4; 95% confidence interval, 3.2-78.7). Patients who received more units of PRBCs during the first 24 hours also had a higher hospital mortality rate (p = 0.03). CONCLUSION: In severely injured trauma patients who require administration of packed red blood cells, the amount of transfused blood is independently associated with both the development of ARDS and hospital mortality.     

Age of transfused blood is an independent risk factor for postinjury multiple organ failure

BACKGROUND: Blood transfusion has repeatedly been demonstrated to be an independent risk factor for postinjury multiple organ failure (MOF). Previously believed to represent a surrogate for shock, packed red blood cell (PRBC) transfusion has recently been shown to result in neutrophil priming and pulmonary endothelial cell activation. We have previously observed that the generation of inflammatory mediators is related to the length of PRBC unit storage. The purpose of this study was to determine if age of transfused PRBC is a risk factor for the development of postinjury MOF. METHODS: Using our prospective database of trauma patients at risk for developing MOF, we identified patients who developed MOF (MOF+) and received 6 to 20 units of PRBCs in the first 12 hours following injury. A similar cohort of patients, matched for ISS and transfusion requirement, who did not develop MOF (MOF-) were also identified. The age of each unit of PRBC transfused in the first 6 hours was determined. Multiple logistic regression was performed to determine if age of transfused blood is an independent risk factor. RESULTS: Sixty-three patients were identified, 23 of whom were MOF+. There was no difference in ISS and transfusion requirement between MOF+ and MOF- groups. MOF+ patients, however, were significantly older (46+/-4.7 years versus 33+/-2.3 years). Moreover, mean age of transfused blood was greater in the MOF+ patients (30.5+/-1.6 days versus 24+/-0.5 days). Similarly, the mean number of units older than 14 and 21 days old were greater in the MOF+ patients. Multivariate analysis identified mean age of blood, number of units older than 14 days, and number of units older than 21 days as independent risk factors for MOF. CONCLUSION: The age of transfused PRBCs transfused in the first 6 hours is an independent risk factor for postinjury MOF. This suggests that current blood bank processing and storage technique should be reexamined. Moreover, fresh blood may be more appropriate for the initial resuscitation of trauma patients requiring transfusion.     

Outcome Analysis of Blood Product Transfusion in Trauma Patients: A Prospective,Risk-Adjusted Study

BACKGROUND: Studies have confirmed adverse outcome associated with transfusion of packed red blood cells (PRBCs) in trauma; however, little data are available regarding other blood product transfusion, such as fresh frozen plasma (FFP) and platelets. The objective of this study was to examine risk-adjusted outcome in trauma with stratification by blood product type. METHODS: Prospective data were collected daily for 1,172 consecutive trauma patients admitted to the intensive care unit (ICU) during a 2-year period, including transfusion rates of blood products (PRBCs, FFP, platelets). Outcome assessment included infection rate, ventilator days (Vdays), ICU and hospital length of stay (LOS), and mortality. RESULTS: Blood products were transfused in 786 (67%) patients. The study cohort had a mean age of 43 +/- 21 years and Injury Severity Score (ISS) of 24 +/- 13. Although the majority of patients were men, women were more likely to be transfused (p < 0.001). Mean transfusion rates of PRBCs (5.5 +/- 9.6 U), FFP (5.4 +/- 11.4), and platelets (3.7 +/- 11.1) were high. Univariate analysis identified that blood product transfusion (any type) was associated with a significantly greater infection rate (34% vs. 9.4%; p < 0.001), hospital LOS (18.6 vs. 9 days; p < 0.001), ICU LOS (13.7 vs. 7.4 days; p < 0.001), Vdays (12.9 vs. 6.3 days; p < 0.001), and mortality (19% vs. 8.3%; p < 0.001). Multivariate analysis (risk-adjusted for severity of injury by ISS, age, sex, and race, and stratified by blood product type) confirmed that risk of infection increased by 5%, and hospital LOS, ICU LOS, and Vdays increased by 0.64, 0.42, and 0.47 days, respectively, for every unit of PRBCs given. Risk of death increased by 3.5% for every unit of FFP transfused. CONCLUSION: There is a dose-dependent correlation between blood product transfusion and adverse outcome (increased mortality and infection) in trauma patients.     

Massive blood transfusion and trauma resuscitation

AIMS: To review the massive transfusion practice at a Level I adult Trauma Centre during initial trauma reception and resuscitation. METHODS: All trauma patients presenting to The Alfred Emergency & Trauma Centre and receiving a transfusion of five units or more of packed red blood cells within 4h of presentation over a 26-month period were included in this study. Patient demographics, clinical characteristics, injuries, surgical management and volume of blood transfused were analysed with mortality as the primary endpoint. Initial clinical features and injuries predictive of massive transfusion were also analysed. RESULTS: There were 119 patients who received a transfusion of five units or more of packed red blood cells (PRBCs) within 4h of presentation. The median Injury Severity Score of this group of patients was 34.0 (IQR 26-48) and mortality was 27.7%. The median number of packed red blood cell transfused was 8.0 (IQR 6-14) in the 1st 4h. Initial clinical features and injuries independently associated with a larger volume of blood transfused were initial hypotension, fractures of the pelvis, kidney injuries, initial acidaemia, and thrombocytopaenia. The Injury Severity Score, initial coagulopathy measured by APTT and the presence of head injuries were the independent predictors of mortality. CONCLUSIONS: The volume of blood transfused during trauma resuscitation was not found to be an independent predictor of mortality. Prospective studies into transfusion practice and clinical features of patients during the trauma resuscitation phase requiring massive transfusion are needed to establish evidence-based guidelines for massive transfusion.     

Achieving optimal massive transfusion ratios: The trauma white board,whole blood,and liquid plasma. Real world low-tech solutions for a high stakes issue

BackgroundIt is well established that achieving optimal ratios of packed red blood cells (PRBC) to fresh frozen plasma (FFP) to platelet ratios during massive transfusion leads to improved outcomes but is difficult to accomplish.MethodsBetween September 2018 and May 2019 our level 2 trauma center implemented 3 new processes to optimize transfusion ratios during massive transfusion protocol (MTP). Two units of low titer group O whole blood (LTOWB) were added as the first step to our MTP. Second, a dry erase board whiteboard was attached to each fluid warmer for real time recording of transfusions. Last, liquid plasma was incorporated into our MTP. We performed a retrospective review evaluating PRBC:FFP ratios for patients who had the massive transfusion protocol initiated and received 4 or more units of blood.ResultsA total of 50 patients had the massive transfusion protocol initiated and received 4 or more units of PRBCs and/or LTOWB within 4 h of arrival. There were 21 patients evaluated prior to protocol changes and 29 patients after the changes. In the study group mean age, sex, pulse, systolic blood pressure (SBP), and injury severity scale (ISS) on admission were not different. In the pre-protocol (preP) group 90% of patients were blunt trauma and in the post-protocol group (postP) 72% were blunt trauma, p = 0. 22. For the preP group the mean units of PRBCs was 7.6 units and FFP 4.7 units. PostP the mean units of PRBCs was 11.4 units and FFP 10.0 units. PRBC/FFP ratios were 1.7 preP and 1.2 postP, p = 0.0072.ConclusionThe institution of whole blood, use of the trauma white board, and the addition of liquid plasma to our transfusion services have allowed us to approach a 1:1 transfusion ratio during the course of our massive transfusions.     

Anemia management program reduces transfusion volumes, incidence of ventilator-associated pneumonia, and cost in trauma patients

BACKGROUND: Strategies to restrict transfusions are gaining acceptance in critical care. We implemented an anemia management program (AMP) for trauma patients in the Surgical Intensive Care Unit. AMP was based on a transfusion trigger of 7 g/dL hemoglobin once hemodynamic sufficiency was achieved. We hypothesized that AMP would decrease the transfusion of packed red blood cells (PRBCs) and cost without detriment in clinical outcomes. METHODS: Transfusion data were retrospectively collected for all trauma patients treated in our Surgical Intensive Care Unit between July 2002 and December 2003. AMP was implemented in a step-wise fashion during a 6-month period (January to June 2003). Data were compared for the 6-month period before (Group I, July to December 2002) and after (Group II, July to December 2003) complete AMP implementation. Blood transfusion volumes were compared using negative binomial regression. Clinical outcomes (length of stay [LOS], death, myocardial infarction [MI], and ventilator-associated pneumonia [VAP]) were compared using risk ratios. Age, sex, and injury severity score (ISS) were examined as potential confounders. RESULTS: In all, 514 trauma patients were treated during the study period (n = 270 in Group I and n = 244 in Group II). Group I and Group II were similar in age (mean: 43.6 versus 42.9) and ISS (mean: 18.3 versus 17.0). Mean PRBCs per patient transfused decreased from 23.1 units to 17.1 units (p = 0.057), reflecting a 22.5% reduction adjusted for confounders (p = 0.097). Outcome data revealed no differences in LOS (mean: 6.4 versus 5.9, p = 0.920), risk of death (4.1% versus 6.1%, p = 0.158), or MI (0.7% versus 0.8%, p = 0.974), but a significant reduction in the incidence of VAP (8.1% versus 0.8%, p = 0.002). Total PRBC cost decreased during the study period from 503,000 dollars to 397,000 dollars. CONCLUSIONS: An anemia management program appears to be safe when applied in the acute ICU phase of trauma care. Implementation of AMP in the ICU reduced the volume of PRBCs transfused with significant cost savings. No significant differences in length of stay, mortality rate, or MI rate were seen. The significant decrease in the rate of VAP requires further elucidation. Further long-term and larger studies are indicated.     

Gender is an essential determinant of blood transfusion in patients undergoing coronary artery bypass graft procedure

STUDY OBJECTIVE: To determine factors that account for gender difference in the need for blood transfusion in coronary artery bypass graft (CABG) patients. DESIGN: Retrospective study of consecutive patients. SETTING: Anesthesiology department of a teaching hospital. PATIENTS: 253 CABG patients (163 males and 90 females). INTERVENTIONS: Packed red blood cells (PRBCs), platelets, and fresh frozen plasma (FFP) were transfused depending on the need of each patient. MEASUREMENTS AND MAIN RESULTS: For each patient, we recorded the gender, age, weight, height, body surface area (BSA), and duration of surgery. Hematocrit (Hct) levels prior to surgery, end of surgery, and at discharge from the hospital were recorded. PRBC administration and use of FFP and platelets were noted. Differences between the data for female and male patients were evaluated using Student's t-test, Chi-square test, and regression analysis. Approximately 60% female and only 20% male patients received PRBCs intraoperatively, whereas 78% females and only 43% males received PRBCs during their entire hospital stay. On average, females received 1.20 units of PRBCs intraoperatively and 2.38 units during the entire hospital stay, while the males received 0.31 units and 1.36 units for similar periods. Gender differences in PRBC transfusion persisted even when females and males were compared within the same subgroups for age, weight, duration of surgery, and preoperative Hct. PRBC units given intraoperatively had a significant correlation with age and preoperative Hct in females, but they had a significant correlation with age, preoperative Hct, and duration of surgery in males. PRBCs given during the entire hospital stay, however, had significant correlation with age, preoperative Hct, and duration of surgery in both females and males. Multiple logistic regression analysis showed that the probability of a patient receiving or not receiving PRBC transfusion is significantly influenced by age, preoperative PRBC mass, duration of surgery, and gender. CONCLUSION: Gender is an independent essential determinant of blood transfusion in CABG patients, and it may interact with age, weight, preoperative Hct, duration of surgery, and other factors in determining the probability of transfusion.     

Early massive transfusion in trauma patients: Canadian single-centre retrospective cohort study

Purpose

To determine associations between red blood cell (RBC) transfusion and early and late clinical outcomes in massively transfused adult trauma patients.

Methods

A retrospective cohort study (1992–2001) including 260 patients receiving ≥10 RBC units ≤24 hr after admission to a university-affiliated trauma centre. We extracted demographic and clinical data and used multivariable regression to determine independent effects of RBC transfusion on clinical outcomes.

Results

Patients had a high (mean [standard deviation]) injury severity score (ISS) (42.5 [15.1]), a high admission sequential organ failure assessment (SOFA) score (8.4 [3.8]), and a high hospital mortality (58.5%). They received 38 (25–64) (median [interquartile range]) blood components within 48 hr, including 19 (14–28) RBC units. For 143 patients surviving ≥48 hr, the maximum SOFA score was associated with RBC units transfused before 48 hr (linear regression beta coefficient 0.075, P < 0.0001), lower nadir hemoglobin before 48 hr (0.034, P = 0.03), age (0.032, P = 0.015), and admission SOFA (0.59, P < 0.0001). The RBC units transfused by 48 hr were not associated with either hospital mortality (n = 35) among patients surviving ≥48 hr (independent predictors, age [logistic regression odds ratio (OR) 1.06, 95% confidence interval 1.03–1.10], ISS [OR 1.07, 1.02–1.13], and maximum SOFA score [OR 1.56, 1.27–1.93]) or 48-hr mortality (n = 117) (independent predictors, admission SOFA [1.65, 1.45–1.88] and later year of hospital admission [OR 1.15, 1.02–1.29]).

Conclusions

Hospital mortality is high among massively transfused trauma patients. Among early survivors, 48-hr RBC transfusion volume is associated with increased organ dysfunction, but not hospital mortality. Also, it is not associated with 48-hr mortality. Future research should continue to explore methods to improve hemostasis and minimize the need for RBC transfusion.     

The effects of protocolized use of recombinant factor VIIa within a massive transfusion protocol in a civilian level I trauma center

Despite conflicting data regarding its effectiveness, many massive transfusion protocols (MTPs) include recombinant Factor VIIa (rFVIIa) as an adjunct to hemorrhage control. Over a 3-year period, outcome data for massively transfused patients was compared based on administration of rFVIIa as part of a mature MTP. Of 228 MTP activations, 117 patients were candidates for rFVIIa, and, of these, 39 patients received rFVIIa under the MTP. Comparing patients who received rFVIIa with those who did not based on initial packed red blood cell (PRBC) transfusion requirements, there was no difference in mortality for transfusions ≤ 20 units (25 vs 24%, 24-hour; 25 vs 42%, 30-day) or 21 to 30 units (33 vs 47%, 24-hour; 55 vs 50%, 30-day). For initial requirement ≥ 30 units of PRBCs, 24-hour mortality (26 vs 64%, P = 0.02) was significantly decreased in patients that received rFVIIa (n = 19) compared with those who did not (n = 17). These mortality differences were not maintained at 30 days (68 vs 71%). rFVIIa had minimal clinical impact on outcomes for patients requiring less than 30 units of PRBCs. For patients transfused more than 30 units of PRBCs, differences in 24-hour and 30-day mortality suggest that rFVIIa converted early deaths from exsanguination to late deaths from multiorgan failure.     

Massive donor transfusion potentially increases recipient mortality after lung transplantation

Objective

Donor blood transfusion has been identified as a potential risk factor for primary graft dysfunction and by extension early mortality. We sought to define the contributing risk of donor transfusion on early mortality for lung transplant.

Microchimerism and renal transplantation: doubt still persists

OBJECTIVE: We sought to study microchimerism in a group of kidney transplant recipients. MATERIALS AND METHODS: In this study, the peripheral blood microchimerism (PBM) after renal transplantation was retrospectively evaluated in 32 male-to-female recipients of living unrelated or cadaveric donor renal transplants. Using a nested polymerase chain reaction (PCR) amplification specific for SRY region of the Y chromosome, microchimerism was detected with a sensitivity of 1:1,000,000. Recipients were compared according to the presence of PBM, acute and chronic rejection episodes, type of allotransplant, recipient and donor age at transplantation, previous male labor or blood transfusion, allograft function (serum creatinine level), and body mass index. RESULTS: Among 32 recipients, 7 (21.9%) were positive for PBM upon multiple testing at various posttransplant times. All microchimeric recipients had received kidneys from living unrelated donors. No significant difference was observed with regard to other parameters. In addition the acute rejection rate in the microchimeric group was 3 (42%) versus 4 (16%) in the nonmicrochimeric recipients (not significant). CONCLUSION: Our results suggested better establishment of microchimerism after living donor kidney transplantation. However, doubt persists concerning the true effect of microchimerism after renal transplantation. It seems that microchimerism alone has no major protective role upon renal allograft survival.     

Real-time sequence-specific primer polymerase chain reaction amplification of HLA class II alleles: a novel approach to analyze microchimerism

The careful assessment of microchimerism is essential to investigate the effects of donor bone marrow-derived cells in transplantation. We have developed a protocol to assess microchimerism based on the HLA mismatch between the recipient and the donor. Our approach combines real-time polymerase chain reaction (PCR) with sequence-specific primer PCR (SSP-PCR) to selectively amplify and measure the abundance of donor HLA alleles in DNA samples extracted from the recipient after transplant. To optimize and validate the reliability of this method at different levels of microchimerism, we tested serial dilutions of donor DNA into recipient DNA. We demonstrate that donor alleles can be readily detected and reliably measured at concentrations as low as 0.1%. This method is simple and rapid and could find practical application in the assessment of microchimerism in patients receiving organ or cellular transplants in conjunction with donor bone marrow cells infusion.     

Fresh frozen plasma (FFP) use during massive blood transfusion in trauma resuscitation

Introduction

Recent retrospective studies have found high fresh frozen plasma (FFP) to packed red blood cell (PRBC) ratios during trauma resuscitation to be associated with improved mortality. Whilst this association may be related to a mortality bias present in these studies, there has been an overall tendency towards a 1:1 FFP:PRBC ratio in massive transfusion guidelines worldwide. The aim of this study was to retrospectively review the administration of FFP in patients undergoing massive transfusion during trauma resuscitation, to add to the evidence base for massive transfusion guidelines.

Materials and methods

Multi-trauma patients who were administered blood transfusions of 5 units or more of packed red blood cells (PRBCs) in the first 4 h were included in this study. Mortality was the primary endpoint with length of hospital stay, ICU hours and mechanically ventilated hours secondary endpoints.

Results

There were 331 patients included in this study with a median Injury Severity Score (ISS) of 36 (25-50) and a mortality of 29.9%. There was little change in the ratio of FFP:PRBC transfused per patient from 2005 to 2008. A low FFP:PRBC ratio in the first 4 h of resuscitation, older age, low initial GCS and coagulopathy on presentation were significant independent factors associated with mortality. When deaths in the first 24 h were excluded, the FFP:PRBC ratio had no association with mortality.

Discussion

This study has shown increased initial survival in association with higher FFP:PRBC ratios during massive transfusion in a population with a high proportion of blunt injuries. The association is difficult to interpret because of an inherent survival bias. The optimal ratio of FFP:PRBC during massive transfusion may be different to 1:1 and further prospective research is required. There is now an increasing need for well designed randomised controlled trials to determine the best FFP:PRBC ratio for the resuscitation of blunt multi-trauma patients.     

Are we giving enough coagulation factors during major trauma resuscitation?

Hemorrhage is a major cause of trauma deaths. Coagulopathy exacerbates hemorrhage and is commonly seen during major trauma resuscitation, suggesting that current practice of coagulation factor transfusion is inadequate. Reversal of coagulopathy involves normalization of body temperature, elimination of the causes of disseminated intravascular coagulation (DIC), and transfusion with fresh-frozen plasma (FFP), platelets, and cryoprecipitate. Transfusion should be guided by clinical factors and laboratory results. However, in major trauma, clinical signs may be obscured and various factors conspire to make it difficult to provide the best transfusion therapy. Existing empiric transfusion strategies for, and prevailing teachings on, FFP transfusion appear to be based on old studies involving elective patients transfused with whole blood and may not be applicable to trauma patients in the era of transfusion with packed red blood cells (PRBCs). Perpetuation of such concepts is in part responsible for the common finding of refractory coagulopathy in major trauma patients today. In this review, we argue that coagulopathy can best be avoided or reversed when severe trauma victims are transfused with at least the equivalent of whole blood in a timely fashion.     

Transfusion after coronary artery bypass surgery: the impact of heparin-bonded circuits.

OBJECTIVE: To identify the impact of heparin bonded (Carmeda) circuits on the need for transfusion of packed red blood cells (PRBC) after CABG independent of the influence of patient, procedural, and surgical experience variables. METHODS: A prospective, randomized trial examined the impact of heparin-bonded circuits in 210 patients undergoing coronary artery bypass surgery at Medical Center of Delaware (Christiana Care Health Services). Patients were randomized to either non-bonded circuits or heparin-bonded (Carmeda) circuits. There were no significant differences in patient characteristics between the treatment and control group. A multivariate analysis was performed to identify the independent predictors of both the need for transfusion (logistic) and number of units of PRBC transfused (OLS). RESULTS: The only significant (P < 0.05) independent predictors of need for transfusion were gender (odds ratio (OR) = 0.35 for males), use of anticoagulants prior to surgery (OR = 2.09), cross-clamp time (OR = 1.03 for each extra minute), and use of heparin-bonded circuits (OR = 0.50 for patients in the heparin-bonded; Carmeda, circuit group). The only significant independent predictors of number of PRBCs were anticoagulants prior to surgery, cross-clamp time, catheterization procedure on the same day, body surface area, and use of heparin-bonded circuits. Other patient demographic variables, comorbidities, and surgical variables were not significant independent predictors of the need for transfusion or the number of units transfused. CONCLUSIONS: Several factors influence the probability of transfusion that patients face following coronary artery bypass surgery. The probability of transfusion is 50% less and the number of PRBCs transfused are 1.42 units less when heparin-bonded (Carmeda) circuits are used, adjusted for patient demographics, comorbidities, or surgical variables.     

Thymic microchimerism correlates with the outcome of tolerance-inducing protocols for solid organ transplantation.

This study found that pretransplant infusion of donor peripheral blood leukocytes, either total leukocytes (peripheral blood leukocytes) or peripheral blood mononuclear cells (PBMC), under appropriate immunomodulating conditions was more effective than donor bone marrow (BM) in prolonging the survival of rats that received kidney grafts. A higher percentage of MHCII(+) cells was found in donor PBMC than in BM cells, and depletion of MHCII(+) cells from donor PBMC abolished their tolerogenic potential. By the analysis of microchimerism in rats infused with donor cells and killed at different time points thereafter, the better tolerogenic potential of leukocyte infusion related to a higher capability of these cells to engraft the recipient thymus. PCR analysis on OX6-immunopurified cells revealed the presence of donor MHCII(+) cells in the thymus of these animals. The role of intrathymic microchimerism was reinforced by findings that thymectomy at the time of transplant prevented tolerance induction by donor leukocytes. Donor DNA was found in the thymus of most long-term graft animals that survived, but in none of those that rejected their grafts. The presence of intrathymic microchimerism correlated with graft survival, and microchimerism in other tissues was irrelevant. PCR analysis of DNA from thymic cell subpopulations revealed the presence of donor MHCII(+) cells in the thymus of long-term surviving animals. Thus, in rats, donor leukocyte infusion is better than donor BM for inducing graft tolerance, defined by long-term graft survival, donor-specific T cell hyporesponsiveness, and reduced interferon gamma production. This effect appears to occur through migration of donor MHCII(+) cells in the host thymus.     

A high ratio of plasma and platelets to packed red blood cells in the first 6 hours of massive transfusion improves outcomes in a large multicenter study

Background

In trauma, most hemorrhagic deaths occur within the first 6 hours. This study examined the effect on survival of high ratios of fresh frozen plasma (FFP) and platelets (PLTs) to packed red blood cells (PRBCs) in the first 6 hours.

Methods

Records of 466 massive transfusion trauma patients (≥10 U of PRBCs in 24 hours) at 16 level 1 trauma centers were reviewed. Transfusion ratios in the first 6 hours were correlated with outcome.

Results

All groups had similar baseline characteristics. Higher 6-hour ratios of FFP:PRBCs and PLTs:PRBCs lead to improved 6-hour mortality (from 37.3 [in the lowest ratio group] to 15.7 [in the middle ratio group] to 2.0% [in the highest ratio group] and 22.8% to 19.0% to 3.2%, respectively) and in-hospital mortality (from 54.9 to 41.1 to 25.5% and 43.7% to 46.8% to 27.4%, respectively). Initial higher ratios of FFP:PRBCs and PLTs:PRBCs decreased overall PRBC transfusion.

Conclusions

The early administration of high ratios of FFP and platelets improves survival and decreases overall PRBC need in massively transfused patients. The largest difference in mortality occurs during the first 6 hours after admission, suggesting that the early administration of FFP and platelets is critical.     

Prospective analysis between the therapy of immunosuppressive medication and allogeneic microchimerism after liver transplantation

After liver transplantation, migration of donor-derived hematopoietic cells to recipient can be detected in peripheral blood. This state is termed microchimerism. The aim of this study was to investigate prospectively the presence of allogeneic microchimerism, the occurrence of acute cellular rejection and the level of immunosuppression in transplanted patients. Microchimerism occurrence between 10 days and 12 months after liver transplantation was analyzed in 47 patients aged between 15 and 65 by a two-stage nested PCR/SSP technique to detect donor MHC HLA-DR gene specifically. A pre-transplant blood sample was collected from each patient to serve as individual negative control. Microchimerism was demonstrated in 32 (68%) of the 47 patients; of these, only 10 patients (31.2%) presented rejection. Early microchimerism was observed in 25 patients (78.12%) and late microchimerism in 7 patients (21.8%). Among the patients with microchimerism, 14 were given CyA and 18 were given FK506. In the group without microchimerism, 12 patients were given CyA and 03 were given FK506. There was a significant association between the presence of microchimerism and the absence of rejection (p=0.02) and also between microchimerism and the type of immunosuppression used. Our data indicate that microchimerism and probably differentiation of donor-derived leukocytes can have relevant immunologic effects both in terms of sensitization of recipient and in terms of immunomodulation toward tolerance induction.     

Massive transfusion in trauma: blood product ratios should be measured at 6 hours

Background: Most potentially preventable haemorrhagic deaths occur within 6 h of injury. Conventionally, blood component therapy delivery is measured by 24‐h cumulative totals and ratios. The study aim was to examine the effect of a massive transfusion protocol (MTP) on early (6 h) balanced component therapy. Methods: An 88‐month retrospective clinical study at a level 1 trauma centre was undertaken, examining consecutive trauma patients receiving ≥10 units of packed red blood cells (PRBCs) within 24 h, before (pre‐MTP) and after implementation of MTP. Demographic data, injury severity score (ISS), abbreviated injury scale (AIS), shock parameters, coagulation profile, the need for surgical intervention (<24 h), mortality and intensive care unit length of stay were collected. The ratios of blood products given by 6 h, by 24 h and the time between administrations of components was collected and analysed. Results: Pre‐MTP and MTP patients had similar demographics, shock severity and initial laboratory findings. Despite MTP patients having had a higher ISS (42 ± 12 versus 36 ± 12, P < 0.05) and AIS head score (2.6 ± 1.8 versus 1.6 ± 2.0, P < 0.05), there was no difference in mortality. Area under the curve (AUC) of the MTP period showed earlier delivery of higher median ratios of fresh frozen plasma (FFP)/PRBC (P= 0.004). Similar findings were found for cryoprecipitate/PRBC and platelet/PRBC ratios. By 24 h, the AUC for FFP/PRBC ratios were no different. Discussion: Implementation of MTP resulted in earlier balanced transfusion. The difference between the FFP/PRBC ratios of the two types of resuscitations levelled by 24 h. The efficacy of component therapy delivery should be measured earlier than 24 h.