Towards patient-specific management of trauma hemorrhage: the effect of resuscitation therapy on parameters of thromboelastometry.
ABSTRACT: Essentials The response of thromboelastometry (ROTEM) parameters to therapy is unknown. We prospectively recruited hemorrhaging trauma patients in six level-1 trauma centres in Europe. Blood products and pro-coagulants prevent further derangement of ROTEM results. ROTEM algorithms can be used to treat and monitor trauma induced coagulopathy. SUMMARY: Background Rotational thromboelastometry (ROTEM) can detect trauma-induced coagulopathy (TIC) and is used in transfusion algorithms. The response of ROTEM to transfusion therapy is unknown. Objectives To determine the response of ROTEM profiles to therapy in bleeding trauma patients. Patients/Methods A prospective multicenter study in bleeding trauma patients (receiving ? 4 red blood cell [RBC] units) was performed. Blood was drawn in the emergency department, after administration of 4, 8 and 12 RBC units and 24 h post-injury. The response of ROTEM to plasma, platelets (PLTs), tranexamic acid (TXA) and fibrinogen products was evaluated in the whole cohort as well as in the subgroup of patients with ROTEM values indicative of TIC. Results Three hundred and nine bleeding and shocked patients were included. A mean dose of 3.8 g of fibrinogen increased FIBTEM CA5 by 5.2 mm (IQR: 4.1-6.3 mm). TXA administration decreased lysis by 5.4% (4.3-6.5%). PLT transfusion prevented further derangement of parameters of clot formation. The effect of PLTs on EXTEM ca5 values was more pronounced in patients with a ROTEM value indicative of TIC than in the whole cohort. Plasma transfusion decreased EXTEM clotting time by 3.1 s (- 10 s to 3.9 s) in the whole cohort and by 10.6 s (- 45 s to 24 s) in the subgroup of patients with a ROTEM value indicative of TIC. Conclusion The effects of therapy on ROTEM values were small, but prevented further derangement of test results. In patients with ROTEM values indicative of TIC, the efficacy of PLTs and plasma in correcting deranged ROTEM parameters is possibly more robust.
Project description:Transfusion therapy is associated with increased morbidity, mortality and costs. Conventional coagulation tests (CCT) are weak bleeding predictors, poorly reflecting coagulation in vivo. Thromboelastometry (ROTEM) provides early identification of coagulation disorders and can guide transfusion therapy by goals, reducing blood components transfusion.The aim of this study is to describe coagulation profile of critically ill patients using ROTEM and evaluate the association between CCT and thromboelastometry.This is a retrospective, observational study conducted in medical-surgical intensive care unit (ICU). Adult patients (?18 years) admitted to ICU between November 2012 and December 2014, in whom ROTEM analyses were performed for bleeding management were included in this study. The first ROTEM and CCT after ICU admission were recorded simultaneously. Additionally, we collected data on blood components transfusion and hemostatic agents immediately after laboratory tests results.The study included 531 patients. Most ROTEM tests showed normal coagulation profile [INTEM (54.8%), EXTEM (54.1%) and FIBTEM (53.3%)] with divergent results in relation to CCT: low platelet count (51.8% in INTEM and 55.9% in EXTEM); prolonged aPTT (69.9% in INTEM and 63.7% in EXTEM) and higher INR (23.8% in INTEM and 27.4% in EXTEM). However 16,7% of patients with normocoagulability in ROTEM received platelet concentrates and 10% fresh frozen plasma.The predominant ROTEM profile observed in this sample of critically ill patients was normal. In contrast, CCT suggested coagulopathy leading to a possibly unnecessary allogenic blood component transfusion. ROTEM test may avoid inappropriate allogeneic blood products transfusion in these patients.
Project description:Fibrinogen and prothrombin have been suggested to become rate limiting in trauma associated coagulopathy. Administration of fibrinogen is now recommended, however, the importance of prothrombin to patient outcome is unknown.We have utilized two trauma patient databases (database 1 n?=?358 and database 2 n?=?331) to investigate the relationship of plasma prothrombin concentration on clinical outcome and coagulation status. Database 1 has been used to assess the relationship of plasma prothrombin to administered packed red blood cells (PRBC), clinical outcome and coagulation biomarkers (Prothrombin Time (PT), ROTEM EXTEM Coagulation Time (CT) and Maximum Clot Firmness (MCF)). ROC analyses have been performed to investigate the ability of admission coagulation biomarkers to predict low prothrombin concentration (database 1), massive transfusion and 24 h mortality (database 1 and 2). The importance of prothrombin was further investigated in vitro by PT and ROTEM assays in the presence of a prothrombin neutralizing monoclonal antibody and following step-wise dilution.Patients who survived the first 24 h had higher admission prothrombin levels compared to those who died (94 vs.67 IU/dL). Patients with lower transfusion requirements within the first 24 h (?10 units of PRBCs) also had higher admission prothrombin levels compared to patients with massive transfusion demands (>10 units of PRBCs) (95 vs.62 IU/dL). Admission PT, in comparison to admission ROTEM EXTEM CT and MCF, was found to be a better predictor of prothrombin concentration <60 IU/dL (AUC 0.94 in database 1), of massive transfusion (AUC 0.92 and 0.81 in database 1 and 2 respectively) and 24 h mortality (AUC 0.90 and 0.78 in database 1 and 2, respectively). In vitro experiments supported a critical role for prothrombin in coagulation and demonstrated that PT and ROTEM EXTEM CT are sensitive methods to measure low prothrombin concentration.Our analyses suggest that prothrombin concentration at admission is predictive of mortality and transfusion and indicates that prothrombin and fibrinogen are rate limiting in coagulopathy.Admission PT is predictive of low prothrombin concentration and clinical outcome. PT could therefore be used as a surrogate for prothrombin concentration and further evaluation of point-of-care devices for faster PT analysis is warranted.
Project description:BACKGROUND:Up to 40% of combat casualties with a truncal injury die of massive hemorrhage before reaching a surgeon. This hemorrhage can be prevented with damage control resuscitation (DCR) methods, which are focused on replacing shed whole blood by empirically transfusing blood components in a 1:1:1:1 ratio of platelets:fresh frozen plasma:erythrocytes:cryoprecipitate (PLT:FFP:RBC:CRYO). Measurement of hemostatic function with rotational thromboelastometry (ROTEM) may allow optimization of the type and quantity of blood products transfused. Our hypothesis was that incorporating ROTEM measurements into DCR methods at the US Role 3 hospital at Bagram Airfield, Afghanistan would change the standard transfusion ratios of 1:1:1:1 to a product mix tailored specifically for the combat causality. METHODS:This retrospective study collected data from the Department of Defense Trauma Registry to compare transfusion practices and outcomes before and after ROTEM deployment to Bagram Airfield. Over the course of six months, 134 trauma patients received a transfusion (pre-ROTEM) and 85 received a transfusion and underwent ROTEM testing (post-ROTEM). Trauma teams received instruction on ROTEM use and interpretation, with no provision of a specific transfusion protocol, to supplement their clinical judgment and practice. RESULTS:The pre and post groups were not significantly different in terms of mortality, massive transfusion protocol activation, mean injury severity score, or coagulation measurements. Despite the difference in size, each group received an equal total number of transfusions. However, the post-ROTEM group received a significant increase in PLT and CRYO transfusions ratios, 4× and 2×, respectively. CONCLUSION:The introduction of ROTEM significantly improved adherence to DCR practices. The transfusion differences suggest that aggressive DCR without thromboelastometry data may result in reduced hemostatic support and underestimate the need for PLT and CRYO. Thus, future controlled trials should include ROTEM-guided coagulation management in trauma resuscitation. LEVEL OF EVIDENCE:Therapeutic, level IV.
Project description: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.
Project description:Background:Whole blood viscoelastic testing (VET) devices are routinely used in a variety of clinical settings to assess hemostasis. The Quantra QStat System is a cartridge-based point of care VET device that measures changes in clot stiffness during coagulation and fibrinolysis using ultrasound detection of resonance. The objective of this study was to assess the ability of the Quantra QStat System to detect coagulopathies in trauma patients. Methods:A multicenter observational study was conducted on adult subjects at two level 1 trauma centers. For each subject, whole blood samples were drawn upon arrival to the emergency department and again, in some cases, after administration of blood products and/or antifibrinolytics. Samples were analyzed on the Quantra in parallel to ROTEM delta. The QStat cartridge provides measures of Clot Time (CT), Clot Stiffness (CS), Fibrinogen and Platelet Contributions to clot stiffness (FCS and PCS), and Clot Stability to Lysis (CSL). Data analyses included linear regression of Quantra and ROTEM parameters and an assessment of the concordance of the two devices for the assessment of hyperfibrinolysis. Results:A total of 56 patients were analyzed. 42% of samples had a low QStat CS value suggestive of an hypocoagulable state. The low stiffness values could be attributed to either low PCS, FCS or combination. Additionally, 13% of samples showed evidence of hyperfibrinolysis based on the QStat CSL parameter. Samples analyzed with ROTEM assays showed a lower prevalence of low CS and hyperfibrinolysis based on EXTEM and FIBTEM results. The correlation of CS, FCS and CT versus equivalent ROTEM parameters was strong with r-values of 0.83, 0.79 and 0.79, respectively. Discussion:This first clinical experience with the Quantra in trauma patients showed that the QStat Cartridge was strongly correlated with ROTEM parameters and that it could detect coagulopathies associated with critical bleeding. Level of evidence:Diagnostic test, Level II.
Project description:ABO-incompatible living-donor kidney transplantation (LDKT) requires immunotherapy and plasma exchange therapy (PEX). PEX with albumin replacement fluid reportedly decreases fibrinogen levels. However, no reports have described the effects of PEX with albumin replacement fluid on blood coagulation parameters and blood loss during the perioperative period. Therefore, we investigated the effects of preoperative PEX on blood coagulation parameters and blood loss during the perioperative period in patients undergoing ABO-incompatible LDKT as measured by rotational thromboelastometry (ROTEM®).Twenty-eight patients undergoing LDKT were divided into the PEX group (ABO incompatible with PEX, n?=?13) and non-PEX group (ABO compatible without PEX, n?=?15). ROTEM® parameters, standard laboratory test parameters, bleeding volume, and transfusion volume were compared between PEX and non-PEX group. MCEplatelet, which represents platelet contribution to clot strength and where "MCE" stands for maximum clot elasticity, was calculated from the difference in MCE between EXTEM and FIBTEM.The bleeding volume during surgery and the intensive care unit (ICU) stay was significantly higher in the PEX than non-PEX group (p?<?0.01). Maximum clot firmness (MCF) of EXTEM (MCFEXTEM), MCFFIBTEM, and MCEplatelet was significantly lower in the PEX than non-PEX group (p?<?0.01). In the PEX group, the bleeding volume during surgery was very strongly correlated with the baseline MCFEXTEM and MCEplatelet, and the bleeding volume during the ICU stay was strongly correlated with the postoperative MCFEXTEM and MCEplatelet.These results suggest that the increased blood loss in the PEX group during surgery and the ICU stay was associated with decreased platelet contribution to clot strength as measured by ROTEM®.UMIN-Clinical Trial Registry UMIN000018355 . Registered 21 July 2015.
Project description:The diagnostic criteria for disseminated intravascular coagulation (DIC) established by the Japanese Association for Acute Medicine (JAAM) is able to diagnose DIC accurately and promptly. The aim of this retrospective study is to evaluate the degree of association between each parameter of JAAM DIC criteria and the diagnosis of trauma induced DIC (T-DIC) utilizing thromboelastometry (ROTEM).Trauma patients transported to our hospital with ROTEM performed in the emergency department between January 2013 and December 2015 were enrolled in this study. We evaluated (1) the characteristics of T-DIC, (2) the relationships between T-DIC and each parameter of the JAAM DIC criteria and (3) the diagnostic accuracies of each parameter for T-DIC by statistical measurement.All 72 patients (21 T-DIC and 51 control) were included in primary analysis. T-DIC was significantly related to younger age, more severe trauma scores, more cases of massive transfusions, and remarkable coagulation abnormality detected by standard coagulation tests. In the cases of T-DIC, ROTEM showed longer clotting time, lower acceleration, lower clot firmness, and inhibited fibrinolysis in EXTEM/INTEM. Within the JAAM DIC score, PT-INR ≥1.2 was the most accurate factor for T-DIC diagnosis; sensitivity 60.0%, specificity 100.0%, and accuracy 88.7%. PT-INR ≥1.2 was statistically correlated with the JAAM DIC score (p < 0.001, r = 0.709). The univariate analysis based on 1.2 of PT-INR indicated statistical differences in most categories of ROTEM, which is similar to analysis performed for the presence and absence of T-DIC.Among JAAM DIC criteria, the PT-INR ≥1.2 was the most accurate factor for both the diagnosis of T-DIC and the evaluation of its severity.
Project description:Platelets (PLTs) are usually stored for up to 5 days prior to transfusion, although in some blood services the storage period is extended to 7 days. During storage, changes occur in both PLT and storage medium, which may lead to PLT activation and dysfunction. The clinical significance of these changes remains uncertain.We performed a systematic review to assess the association between PLT storage time and clinical or transfusion outcomes in patients receiving allogeneic PLT transfusion. We searched studies published in English between January 2000 and July 2017 identified from MEDLINE, Embase, PubMed and the Cochrane Libraries.Of the 18 studies identified, five included 4719 critically ill patients (trauma, post-cardiac surgery and a heterogeneous population of critically ill patients) and 13 included 8569 haematology patients. The five studies in critically ill patients were retrospective and did not find any association between PLT storage time when PLTs were stored for up to 5 days and mortality. There was also no association between older PLTs and sepsis in the two largest studies (n?=?4008 patients). Of the 13 studies in haematology patients, seven analysed prolonged storage time up to 6.5 or 7 days. Administration of fresh PLTs (less than 2 or 3 days) was associated with a significant increase in corrected count increment (CCI) compared to older PLTs in seven of the eight studies analysing this outcome. One single centre retrospective study found an increase in bleeding events in patients receiving older PLTs.PLT storage time does not appear to be associated with clinical outcomes, including bleeding, sepsis or mortality, in critically ill patients or haematology patients. The freshest PLTs (less than 3 days) were associated with a better CCI, although there was no impact on bleeding events, questioning the clinical significance of this association. However, there is an absence of evidence to draw definitive conclusions, especially in critically ill patients.
Project description:The prothrombotic state in type 1 diabetes mellitus (T1DM) has been reported as a plausible cause of vascular complications. Rotational thromboelastometry (ROTEM) assay enables the global assessment of coagulation status. This study aimed to assess hypercoagulability in children with T1DM using ROTEM. A total of 43 T1DM children (20 females and 23 males) aged 2-18 years and age- and sex-matched 30 healthy control subjects were enrolled in the study group. ROTEM assays [intrinsic TEM (INTEM) and extrinsic TEM (EXTEM)] were used to measure and analyze coagulation time (CT), clot formation time, maximum clot firmness (MCF). Glycated hemoglobin levels (HbA1c), diabetic complications, platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, and dimerized plasmin fragment D (D-dimer) were determined in the study group. The mean duration of T1DM diagnosis was 3.15 ± 2.49 years, and the mean HbA1c level was 8.94 ± 1.88% (74.29 ± 20.59 mmol/mol). None of the patients had macrovascular complications. Nephropathy was present in five patients. In the T1DM group, EXTEM-CT [80.00 (66.75-108.50)] was significantly lower, and EXTEM-MCF [65.00 (64.00-70.00)] and INTEM-MCF [65.00 (62.00-68.00)] were significantly higher than in the controls (p < 0.001, p = 0.026, and p = 0.004, respectively). However, the duration of T1DM and the degree of metabolic control had no influence on these parameters. Platelet count, PT, aPTT, fibrinogen and D-dimer levels were comparable between the diabetic patients and the control group. There were statistically significant correlations between fibrinogen level and INTEM-MCF and EXTEM-MCF (p < 0.001, p = 0.002 and r = 0.545, r = 0.454, respectively) This study shows that decreased levels of CT and increased levels of MCF suggest hypercoagulability in patients with T1DM. Further studies are needed to confirm our findings on a larger number of diabetic patients.
Project description:Argatroban or lepirudin anticoagulation therapy in patients with heparin induced thrombocytopenia (HIT) or HIT suspect is typically monitored using the activated partial thromboplastin time (aPTT). Although aPTT correlates well with plasma levels of argatroban and lepirudin in healthy volunteers, it might not be the method of choice in critically ill patients. However, in-vivo data is lacking for this patient population. Therefore, we studied in vivo whether ROTEM or global clotting times would provide an alternative for monitoring the anticoagulant intensity effects in critically ill patients.This study was part of the double-blind randomized trial "Argatroban versus Lepirudin in critically ill patients (ALicia)", which compared critically ill patients treated with argatroban or lepirudin. Following institutional review board approval and written informed consent, for this sub-study blood of 35 critically ill patients was analysed. Before as well as 12, 24, 48 and 72 h after initiation of argatroban or lepirudin infusion, blood was analysed for aPTT, aPTT ratios, thrombin time (TT), INTEM CT,INTEM CT ratios, EXTEM CT, EXTEM CT ratios and maximum clot firmness (MCF) and correlated with the corresponding plasma concentrations of the direct thrombin inhibitor.To reach a target aPTT of 1.5 to 2 times baseline, median [IQR] plasma concentrations of 0.35 [0.01-1.2] μg/ml argatroban and 0.17 [0.1-0.32] μg/ml lepirudin were required. For both drugs, there was no significant correlation between aPTT and aPTT ratios and plasma concentrations. INTEM CT, INTEM CT ratios, EXTEM CT, EXTEM CT ratios, TT and TT ratios correlated significantly with plasma concentrations of both drugs. Additionally, agreement between argatroban plasma levels and EXTEM CT and EXTEM CT ratios were superior to agreement between argatroban plasma levels and aPTT in the Bland Altman analysis. MCF remained unchanged during therapy with both drugs.In critically ill patients, TT and ROTEM parameters may provide better correlation to argatroban and lepirudin plasma concentrations than aPTT.ClinicalTrials.gov , NCT00798525 , registered on 25 Nov 2008.