Kirsten Balvers

Combined effect of therapeutic strategies for bleeding injury on early survival, transfusion needs and correction of coagulopathy.

The combined effects of balanced transfusion ratios and use of procoagulant and antifibrinolytic therapies on trauma‐induced exsanguination are not known. The aim of this study was to investigate the combined effect of transfusion ratios, tranexamic acid and products containing fibrinogen on the outcome of injured patients with bleeding.

Hypothermia as a predictor for mortality in trauma patients at admittance to the Intensive Care Unit.

Aims: To study the impact of hypothermia upon admission to the Intensive Care Unit (ICU) on early and late mortality and to develop a prediction model for late mortality in severely injured trauma patients. Materials and Methods: A multicenter retrospective cohort study was performed in adult trauma patients admitted to the ICU of two Level-1 trauma centers between 2007 and 2012. Hypothermia was defined as a core body temperature of ≤35° Celsius. Logistic regression analyses were performed to quantify the effect of hypothermia on 24-hour and 28-day mortality and to develop a prediction model. Results: A total of 953 patients were included, of which 354 patients had hypothermia (37%) upon ICU admission. Patients were divided into a normothermic or hypothermic group. Hypothermia was associated with a significantly increased mortality at 24 hours and 28 days (OR 2.72 (1.18-6.29 and OR 2.82 (1.83-4.35) resp.). The variables included in the final prediction model were hypothermia, age, APACHE II score (corrected for temperature), INR, platelet count, traumatic brain injury and Injury Severity Score. The final prediction model discriminated between survivors and non-survivors with high accuracy (AUC = 0.871, 95% CI 0.844-0.898). Conclusions: Hypothermia, defined as a temperature ≤35° Celsius, is common in critically ill trauma patients and is one of the most important physiological predictors for early and late mortality in trauma patients. Trauma patients admitted to the ICU may be at high risk for late mortality if the patient is hypothermic, coagulopathic, severely injured and has traumatic brain injury or an advanced age.

Endogenous microparticles drive the proinflammatory host immune response in severely injured trauma patients.

ABSTRACT Introduction: Severe trauma affects the immune system, which in its turn is associated with poor outcome. The mediators driving the immune responses in trauma are largely unknown. The aim of this study was to investigate the role of endogenous microparticles (MPs) in mediating the immune response following severe trauma. Methods: A prospective, observational substudy of the ACIT II (Activation of Coagulation and Inflammation in Trauma II) study was performed at our academic level I trauma center. Adult multiple-trauma patients with an injury severity score of 15 or higher were included between May 2012 and June 2013. Ex vivo whole-blood stimulation with lipopolysaccharide was performed on aseptically collected patient plasma containing MPs and in plasma depleted of MPs. Flow cytometry and transmission electronic microscopy were performed on plasma samples to investigate the numbers and cellular origin of MPs. Healthy individuals served as a control group. Results: Ten trauma patients and 10 control subjects were included. Trauma patients were significantly injured with a median injury severity score of 19 (range, 17–45). Patients were neither in shock nor bleeding. On admission to the hospital, the host response to bacterial stimulation was blunted in trauma patients compared with control subjects, as reflected by decreased production of interleukin 6 (IL-6), IL-10, and tumor necrosis factor &agr; (P < 0.001). In trauma patients, MP-positive plasma was associated with a significantly higher synthesis of IL-6 and tumor necrosis factor &agr; compared with plasma depleted from MPs (P = 0.047 and 0.002, respectively). Compared with control subjects, the number of circulating MPs was significantly decreased in trauma patients (P = 0.009). Most MPs originated from platelets. Multiple cellular protrusions, which result in MP formation, were observed in plasma from trauma patients, but not in control subjects. Conclusions: On admission, trauma patients have a reduced immune response toward endotoxin challenge, which is, at least in part, mediated by MPs, which circulate in low numbers and in early stages. Most MPs originate from platelets, which indicates that these cells may be the most important source of MPs involved in initiating an inflammatory host response after injury.

Effects of a hospital-wide introduction of a massive transfusion protocol on blood product ratio and blood product waste

Background: Massive transfusion protocols (MTPs) are increasingly used in the transfusion practice and are developed to provide the standardized and early delivery of blood products and procoagulant agents and to supply the transfusion of blood products in a well-balanced ratio. Aim: The aim of this study was to investigate the effect of a hospital-wide introduction of an MTP on blood product ratio and a waste of blood products. Materials and Methods: Retrospective analysis was performed to compare the transfusion practice in massive bleeding patients before and after the introduction of an MTP and between the use of an MTP and transfusion off-protocol. Massive bleeding was defined as an administration of ≥5 units of red blood cells (RBCs) within 12 h. Results: Of 547 massively transfused patients, 192 patients were included in the pre-MTP period and 355 patients in the MTP period. The ratio of RBC to fresh frozen plasma (FFP) and the platelets transfused shifted significantly toward 1:1:1 in the MTP period (P = 0.012). This was mainly caused by a shift in RBC: FFP ratio (P = 0.014). An increase in the waste of blood products was observed, most notably FFPs (P = 0.026). Extending the storage time after thawing reduced the waste of FFPs from 11% to 4%. Conclusion: Hospital-wide introduction of an MTP is an adequate way to achieve a well-balanced transfusion ratio of 1:1:1. This comes at the cost of an increase in the waste of FFPs, which is lowered after extending the duration of storage time after thawing.

Risk factors for trauma-induced coagulopathy- and transfusion-associated multiple organ failure in severely injured trauma patients.

Background Both trauma-induced coagulopathy (TIC) and transfusion strategies influence early outcome in hemorrhagic trauma patients. Their impact on late outcome is less well characterized. This study systematically reviews risk factors for TIC- and transfusion-associated multiple organ failure (MOF) in severely injured trauma patients. Materials and methods A systematic search was conducted in PubMed and Embase. Studies published from 1986 to 2013 on adult trauma patients with an injury severity score ≥16, investigating TIC or transfusion strategies with MOF as primary or secondary outcome, were eligible for inclusion. Results of the included studies were evaluated with meta-analyses of pooled data. Results In total, 50 studies were included with a total sample size of 63,586 patients. Due to heterogeneity of the study populations and outcome measures, results from 7 studies allowed for pooling of data. Risk factors for TIC-associated MOF were hypocoagulopathy, hemorrhagic shock, activated protein C, increased histone levels, and increased levels of markers of fibrinolysis on admission. After at least 24 h after admission, the occurrence of thromboembolic events was associated with MOF. Risk factors for transfusion-associated MOF were the administration of fluids and red blood cell units within 24 h post-injury, the age of red blood cells (>14 days) and a ratio of FFP:RBC ≥ 1:1 (OR 1.11, 95% CI 1.04–1.19). Conclusion Risk factors for TIC-associated MOF in severely injured trauma patients are early hypocoagulopathy and hemorrhagic shock, while a hypercoagulable state with the occurrence of thromboembolic events later in the course of trauma predisposes to MOF. Risk factors for transfusion-associated MOF include administration of crystalloids and red blood cells and a prolonged storage time of red blood cells. Future prospective studies investigating TIC- and transfusion-associated risk factors on late outcome are required.

Are there any alternatives for transfusion of AB plasma as universal donor in an emergency release setting

AB plasma is used as the universal donor plasma product in patients requiring massive transfusion. However, currently it is a recommended policy to transfuse plasma derived from male donors only as transfusion of plasma from HLA antibody–positive female donors is associated with an increased risk for transfusion‐related acute lung injury. As a result, due to high demands, supplies of blood banks may run out of AB plasma, calling for alternatives. Therefore, the aim of this review was to investigate alternatives for emergency release of AB plasma as the universal donor.