EXTEM MCF Research Articles

Variability of fibrinolytic activity in pregnant patients exposed to tissue plasminogen activator: an in vitro study utilizing rotational thromboelastometry

BackgroundThe investigation into the variability of fibrinolysis in obstetric patients is notably limited despite its relevance to postpartum hemorrhage. We investigate an in vitro model of fibrinolysis measured by rotational thromboelastrometry (ROTEM) in maternal blood samples with lysis stimulated by tissue plasminogen activator (tPA). MethodsWritten informed consent was obtained from 19 patients at term pregnancy during admission to the labor and delivery unit. Patients who were taking medication affecting coagulation were excluded. Tissue plasminogen activator was added to whole blood samples to a final concentration of 100 or 220 ng/mL prior to ROTEM testing. ResultsThe addition of tPA produced high intra-individual fibrinolytic variability for clot firmness and lysis parameters. Patients responded differently to each tPA dose ranging from clot lysis within the range of 0 ng/mL tPA group to complete clot lysis. The coefficient of variation (CV) values for the 220 ng/mL tPA group were: EXTEM MCF 0.510, EXTEM LI30 1.601, FIBTEM MCF 0.349, FIBTEM LI30 2.097. CV values for the 100 ng/mL tPA group were: EXTEM MCF 0.144, EXTEM LI30 1.038, FIBTEM MCF 0.096, FIBTEM LI30 1.238. ConclusionWe demonstrate a wide range of fibrinolytic response in the obstetric population to exogeneous tPA. We found subgroups of patients that were very responsive to tPA and insensitive to tPA. This study represents a preliminary exploration into classifying the obstetric fibrinolytic phenotypes. Further research will integrate relevant coagulation factors to establish a predictive model for testing susceptibility to lysis that can be applied at the point of care.

Abstract TP158: Baseline Viscoelastic Hemostatic Assays and Associations With Poor Long-Term Intracerebral Hemorrhage Outcomes

Introduction: Viscoelastic hemostatic assays can detect coagulopathy relevant for intracerebral hemorrhage (ICH) patients at risk for hematoma expansion. However, it is unclear whether these assays associate with long term ICH outcomes. We sought to assess whether baseline coagulopathy detectable via viscoelastic hemostatic assay associates with poor 6-month neurological outcomes after ICH. Methods: Spontaneous ICH patients enrolled in a single-center prospective observational study from 2013 to 2020 who received baseline viscoelastic hemostatic assay testing via Rotational Thromboelastometry (ROTEM) were included. Patients with prior anticoagulant use were excluded. ROTEM assessments of coagulation kinetics and clot strength were the primary exposure variables. Poor 6-month neurological outcome was defined as modified Rankin Scale (mRS) 4-6. Multivariable logistic regression analyses assessed the relationships of ROTEM parameters with 6-month outcomes after adjusting for ICH score, hemoglobin, and sex. Results: Of 44 patients included for analysis, the mean age was 64, 57% were female, 52% had deep ICH, and the median ICH volume was 23.3 mL. Poor 6-month outcome was seen in 61%. We identified that slower coagulation kinetics was associated with poor 6-month outcome as assessed in both extrinsic and intrinsic pathways (EXTEM CFT: adjusted OR 1.06, 95% CI: 1.02-1.12, p=0.02; INTEM CFT: adjusted OR 1.05, 95% CI: 1.01-1.10, p=0.05, respectively). Weaker clot strength was also associated with poor 6-month outcome (EXTEM MCF: adjusted OR 0.78, 95% CI: 0.59-0.93, p=0.03; INTEM MCF: adjusted OR 0.83, 95% CI: 0.68-0.97). We did not identify similar relationships using conventional coagulation assays (ie., PT/PTT/INR, platelet count). Conclusions: We identified that baseline impaired coagulation kinetics and weaker clot strength seen using ROTEM testing associate with poor 6-month ICH outcomes. Further work is needed to clarify the generalizability of these findings and the mechanisms driving these relationships to assess whether viscoelastic guided therapies can potentially be used to improve long-term ICH outcomes.

In vitro comparison of cold-stored whole blood and reconstituted whole blood.

Cold-stored whole blood (CSWB) is increasingly used in damage control resuscitation. Haemostatic function of CSWB seems superior to that of reconstituted whole blood, and it is sufficiently preserved for 14-21 days. To provide evidence for a yet insufficiently studied aspect of prehospital CSWB use, we compared in vitro haemostatic properties of CSWB and currently used in-hospital and prehospital blood component therapies. Blood was obtained from 24 O RhD positive male donors. Three products were prepared: CSWB, in-hospital component therapy (red blood cells [RBCs], OctaplasLG and platelets 1:1:1) and prehospital component therapy (RBCs and lyophilized plasma 1:1). Samples were drawn on days 1 and 14 of CSWB or RBC cold storage. On day 14, platelet concentrates at their expiry (5 days) were used for 1:1:1 mixing. Conventional clotting assays, rotational thromboelastometry, thrombin formation and platelet function were assessed. Haemoglobin, platelet count, fibrinogen and coagulation factor levels remained closest to physiological in CSWB. Factor VIII activity decreased markedly by day 14 in CSWB. The decline in platelet function was prominent in CSWB. However, CSWB on day 14 yielded physiological EXTEM MCF, suggesting haemostatically sufficient platelet function. Despite haemodilution and lower coagulation factor levels, in-hospital component therapy was haemostatically adequate. Prehospital component therapy formed the weakest clots. Thrombin formation potential remained comparable and stable in all groups. Current prehospital component therapy fails to offer the clotting potential that CSWB does. CSWB and current in-hospital 1:1:1 component therapy show similar haemostatic potential until 14 days of storage.

THE QUANTRA PCS, PLATELET CONTRIBUTION TO CLOT STIFFNESS, PARAMETER IS CLINICALLY USEFUL TO IDENTIFY PLATELET-DEPENDENT BLEEDING IN HIGH-RISK CARDIAC SURGERY PATIENTS

<h3>Objective</h3> Postoperative use of platelet function testing in order to rule out microvascular bleeding due to platelet dysfunction after cardiac surgery still lacks strong reference data and reliable cut-off values. We investigated the performance of two different point-of-care viscoelastic devices and platelet aggregometry in expressing surgery-dependent platelet dysfunction and anticipating postoperative major bleeding in a cohort of high-risk patients. <h3>Design and Method</h3> This is a prospective cohort study on 50 adult patients who underwent cardiac surgery with cardiopulmonary bypass (CPB) being on antiplatelet drugs discontinued for no more than 7 days (clopidogrel, prasugrel) or 5 days (ticagrelor). Coagulation and platelet function testing, including QUANTRA, ROTEM and Multiplate were assessed preoperatively and postoperatively. Chest drain blood loss was measured in the first 12 postoperative hours. Perioperative bleeding was assessed using the Universal Definition of Perioperative Bleeding (UDPB) in cardiac surgery, modified to not consider anemia-correcting packed red cells transfusions in absence of bleeding > 600 ml/12 h. Major bleeding was identified as UDPB class II or higher. <h3>Results</h3> The QUANTRA Platelet contribution to Clot Stiffness (PCS) was significantly (P=0.001) reduced after CPB. Multiplate ADPtest was significantly (P=0.001) reduced, as well, whereas TRAPtest was not. The platelet component (PC) as extrapolated by ROTEM data (EXTEM MCF – FIBTEM MCF) was unchanged after CPB, while the A10 PC (PC at 10 minutes) significantly (P=0.001) decreased. At regression analysis of the preoperative and postoperative platelet function parameters, there was a significant linear correlation (P=0.001) for the PCS, A10 PC and ADPtest. At the ROC analysis for the predictive ability of the post-CPB platelet function testing, the best discrimination was obtained by the QUANTRA PCS, with an AUC of 0.788, followed by the ROTEM A10 PC (AUC 0.765) and PC (AUC 0.758). The Multiplate tests did not achieve an AUC > 0.70. The cut off values identified for the QUANTRA PCS (10.5 hPa), the ROTEM A10 PC (38 mm) and for the ROTEM PC (47 mm) yielded a combination of a negative predictive value > 80% and a positive predictive value > 67%. <h3>Conclusions</h3> QUANTRA PCS, ROTEM A10 PC, and Multiplate ADPtest reflect the post-CPB platelet dysfunction, whereas ROTEM PC and Multiplate TRAPtest do not. Major bleeding was predicted with a moderate degree of discrimination by the post-CPB viscoelastic tests (PCS, PC, A10 PC) but not by the Multiplate tests.

Assessment of Coagulation Profiles by Rotational Thromboelastometry in COVID 19 Patients.

According to recent studies, thrombotic complications frequently occur in Coronavirus Disease-19 (COVID-19) and are associated with increasing disease severity and poor prognosis. However, conventional coagulation assays are unable to identify these patients' hypercoagulable states, raising questions about the appropriate assessment tool. We aimed to evaluate coagulation abnormalities in patients with different severity of CO-VID-19 using viscoelastic tests. This was a single center retrospective observational study in a group of 50 adult patients with SARS-COV-2 infection and different severity of pneumonia (20 moderate, 30 severe). Coagulation status was evaluated using rotational thromboelastometry (ROTEM®) in conjunction with conventional coagulation assays (platelet count, PT, aPTT, fibrinogen, and D-dimer levels). Shorter than normal EXTEM CFT, higher than normal A10 and MCF in INTEM, EXTEM, and FIBTEM and higher than normal α-angle were classified as markers of hypercoagulable state. Forty-four (88%) patients had at least two hypercoagulable ROTEM parameters. Seven patients developed thromboembolic complications. All were classified as having severe COVID-19 pneumonia. With increment increases in disease severity, we observed an increase in the number of patients with hypercoagulable parameters and higher INTEM, EXTEM, and FIBTEM MCF but without being statistically significant. On the other hand, we noted a significant decrement of PT (p = 0.039), higher fibrinogen (p = 0.001), higher D dimer (p < 0.001), and shorter CT EXTEM (p < 0.001). Our findings support the presence of a hypercoagulable state in COVID-19 patients, especially in the severe forms. It also highlights the role of viscoelastic tests in assessing COVID-19 coagulopathy and, therefore, their potential use in thrombophrophylactic management.

Comparison of the New Viscoelastic Coagulation Analyzer ClotPro® With ROTEM® Delta and Conventional Coagulation Tests in Critically Ill Patients With COVID-19.

Background: Viscoelastic coagulation testing has been suggested to help manage coagulopathy in critically ill patients with COVID-19. However, results from different viscoelastic devices are not readily comparable. ClotPro® is a novel thromboelastometry analyzer offering a wider range of commercially available assays.Methods: We compared the results from ClotPro with results from the well-established ROTEM® Delta device and conventional coagulation tests in critically ill patients with COVID-19.Results: Viscoelastic parameters indicated the presence of a potentially hypercoagulable state in the majority of patients. In up to 95 paired measurements, we found strong correlations between several parameters routinely used in clinical practice: (i) EX test vs. EXTEM CT, A5, A10, MCF, (ii) IN test vs. INTEM A5, A10, MCF, and (iii) FIB test vs. FIBTEM A5, A10, MCF (all R > 0.7 and p < 0.001). In contrast, IN test CT vs. INTEM CT showed only a moderate correlation (R = 0.53 and p < 0.001). Clot strength parameters of both devices exhibited strong correlations with platelet counts and fibrinogen levels (all R > 0.7 and p < 0.001). Divergent correlations of intrinsically activated assays with aPTT and anti-factor Xa activity were visible. Regarding absolute differences of test results, considerable delta occurred in CT, CFT, and clot strength parameters (all p < 0.001) between both devices.Conclusions: Several parameters obtained by ClotPro show strong correlations with ROTEM Delta. Due to weak correlations of intrinsically activated clotting times and considerable absolute differences in a number of parameters, our findings underline the need for device-specific algorithms in this patient cohort.

Higher coagulation activity in hip fracture patients: A case-control study using rotational thromboelastometry.

Trauma-induced coagulopathy has been extensively investigated in the multitrauma setting, but only sparsely following moderate orthopedic trauma. The purpose of this study was to evaluate changes in the hemostatic profile of patients with hip fractures, using rotational thromboelastometry (ROTEM). 198 patients with hip fractures who underwent surgery were included in the study. A matched group of 52 healthy individuals was also enrolled. Demographics, conventional laboratory assays, and ROTEM parameters were recorded and compared between patients and healthy adults. The preoperative and postoperative ROTEM values of fractured patients were also compared. The conventional coagulation assays were similar for the 2 groups. However, several ROTEM parameters including EXTEM MCF (P<.001), EXTEM alpha angle (P<.001), INTEM MCF (P<.001), INTEM A10 (P<.001), and INTEM alpha angle (P<.001) significantly differed between the 2 groups indicating a higher coagulation potential following hip fractures. Also, fractured patients had significantly lower INTEM and EXTEM CT values (P=.008 and P=.012, respectively) and significantly lower INTEM and EXTEM CFT values (P<.001). Adjusted analysis for confounders further confirmed the direct relationship between hip fracture and higher coagulation activity. Last, INTEM CT and CFT significantly decreased (P=.008 and P<.001, respectively), while INTEM MCF, A10, and alpha angle significantly increased (P<.001) postoperatively, indicating that surgery further increases the coagulation potential. A higher coagulation activity following hip fractures and surgical treatment can be detected by ROTEM shortly after the injury, even when this is undetectable by conventional coagulation assays.

Rotational thromboelastometry (ROTEM) parameters in dogs with haemoperitoneum and their associations with clinical and laboratory signs.

Rotational thromboelastometry (ROTEM) is a viscoelastic coagulation test that allows the evaluation of haemostasis from clot formation to clot dissolution. The aim of this retrospective study was to describe the changes in haemostasis using ROTEM parameters in dogs presenting with spontaneous or traumatic haemoperitoneum and to evaluate any associations between clinical and laboratory parameters at presentation with the ROTEM. We hypothesized that the dogs would show signs of hypocoagulability and hyperfibrinolysis and that these changes would correlate with the degree of hypoperfusion. Clinical records were searched for a period of 5 years for dogs presenting with a haemoperitoneum und for whom a -ROTEM analysis at presentation was carried out. Forty dogs were identified, and various clinical and laboratory parameter (heart rate, blood pressure, blood glucose, lactate, serum albumin concentration, PCV (venous and abdominal), ionized calcium, pH and base excess) were retrieved. The following ROTEM parameters were analysed: extrinsic clotting time (ExTEM CT), clot formation time (ExTEM CFT), clot firmness (ExTEM MCF) and maximum lysis (ExTEM ML), as well as fibrinogen (FibTEM) CT and MCF. Compared to institutional reference intervals, dogs with haemoabdomen showed prolongation of ExTEM and FibTEM CT, ExTEM CFT and 50% were hypocoagulable and 62% thrombocytopenic. No hyperfibrinolysis could be detected. Multiple linear regression models showed an association between decreased base excess, trauma and ROTEM signs for hypocoagulability. Furthermore, age was associated with a stronger fibrin clot. In conclusion, 50% of the dogs presented hypocoagulable and changes in ROTEM parameters are similar to those seen with consumption coagulopathy. Base excess and trauma were associated with hypocoagulability, while increasing age was associated with a stronger fibrin clot.

Effect of 50 mg/kg intravenous tranexamic acid on coagulation assessed by rotational thromboelastometry (ROTEM) in healthy Beagle dogs.

In people, the antifibrinolytic drug tranexamic acid reduces bleeding and the need for blood products with both normal and exaggerated fibrinolysis without increasing the number of thromboembolic events. In dogs, in addition to prevention and treatment of bleeding, higher doses of tranexamic acid can be used to induce vomiting. The objective of this study was to evaluate the effect of a high dose of tranexamic acid on the coagulation of healthy Beagle dogs. A prospective trial was conducted in eight healthy Beagles receiving tranexamic acid for a concurrent trial evaluating different antiemetics. Rotational thromboelastometry (ROTEM) analysis (EXTEM, APTEM, FIBTEM, INTEM) was performed before and 30 minutes after intravenous administration of 50 mg/kg tranexamic acid. ROTEM parameters before and after tranexamic acid administration and between EXTEM and APTEM were compared with Wilcoxon matched-pairs signed rank test and data is presented as median (range). After tranexamic acid administration, FIBTEM clotting time became significantly shorter (p=0.03) from 37 s (28-124 s) to 33 s (27-40 s) and INTEM clot formation time significantly decreased (p=0.02) from 82 s (47-132s) to 60 s (43-107 s). After tranexamic acid APTEM MCF was significantly weaker (p=0.01) with 45 mm (30-63 mm) than EXTEM MCF with 55 mm (43-69 mm) and than APTEM MCF before tranexamic acid with 55 mm (43-69 mm) (p=0.02). All other analysed parameters including maximum lysis did not change after administration of tranexamic acid. The administration of 50 mg/kg intravenous tranexamic acid resulted in small changes in ROTEM profiles without inducing a hypercoagulable clot. In conclusion, tranexamic acid can safely be administered to healthy dogs with normal coagulation profiles. As an additional finding, APTEM parameters measured in the current study do not support the use of this test in dogs.

Effects of Fibrinogen Levels and Platelet Counts on Viscoelastic Testing in Cirrhotic Patients.

IntroductionCirrhotic patients have been considered for decades to have a pro-haemorrhagic pattern and were treated as such based on the results from standard coagulation tests. The aim of our study was to determine the effects of platelet count and fibrinogen levels on rotational thromboelastometry (ROTEM) parameters.MethodsWe prospectively included 176 patients with End-Stage Liver Disease (ESLD) admitted to our Intensive Care Unit prior to liver transplantation. Collected data consisted of severity scores, liver, renal and standard coagulation tests, fibrinogen levels, platelet counts and ROTEM parameters. Four ROTEM assays were performed (ExTEM, InTEM, ApTEM and FibTEM) and the following parameters included: CT – clotting time, CFT – clot formation time, MCF – maximum clot firmness, ML – maximum lysis, alpha angle, TPI – thrombin potential index, MaxV - maximum velocity of clot formation (MaxV), MaxVt - time to MaxV, MCE - maximum clot elasticity and AUC - area under the curve.ResultsStatistical analysis demonstrated a linear correlation between platelet counts and ExTEM TPI (R2 linear =0.494), ExTEM MaxV (R2 linear =0.253), ExTEM MCE (R2 linear = 0.351) and ExTEM MCF (R2 cubic = 0.498). Fibrinogen levels correlated linearly with ExTEM MCF (R2 linear = 0.426), ExTEM TPI (R2 linear = 0.544), ExTEM MaxV (R2 linear = 0.332), ExTEM MCE (R2 linear = 0.395) and non-linearly with ExTEM CFT (R2 cubic = 0.475).ConclusionFibrinogen levels and platelet counts had an important effect on both standard and derived ROTEM parameters. Further analysis is required in order to determine clinically oriented cut-off values below which severe coagulopathy would develop.

Comparison of the efficacy of two human fibrinogen concentrates to treat dilutional coagulopathy in vitro

Both congenital and acquired fibrinogen deficiency can be safely treated with administration of fibrinogen concentrate.The aim of this study was to test the efficacy of a new fibrinogen product (Fibryga) compared to a licensed product (Haemocomplettan) in an in vitro model of dilutional coagulopathy.Ten blood specimens from healthy volunteers were diluted 1:1 with balanced crystalloid solution and subsequently supplemented with each fibrinogen concentrate at a dose replicating in vivo supplementation (50 mg kg−1). Changes in clot firmness (FIBTEM and EXTEM assay), as well as changes in the fibrinogen antigen level, fibrinogen activity, factor XIII level and fibronectin levels were assessed at baseline, after dilution and after adding fibrinogen concentrate.There was no significant difference between the drugs in their in vitro ability to improve clot firmness in the FIBTEM assay (Fibryga: mean MCF 14.4 mm (SD 3.4 mm) vs. Haemocomplettan: MCF 14.1 mm (2.4); p = .584). Fibryga led to significantly higher clot firmness in EXTEM MCF: 56.7 mm (3.8) vs. 53.7 mm (3.7); p < .001). Distinct differences between FXIII levels (significantly higher in Fibryga; mean 40.9% (6.2%) vs. 31.0% (6.2%); p < .001) and fibronectin levels (significantly higher in Haemocomplettan; mean 0.008 g L−1 (SD 0.002 g L−1) vs. 0.002 g L−1 (SD 0.002 g L−1; p < .001) were observed between products.This is the first study to demonstrate that Fibryga and Haemocomplettan have similar efficacy in improving clot firmness in a dilutional hypofibrinogenemia model in vitro.

In vitro evaluation of canine hemostasis following dilution with hydroxyethyl starch (130/0.4) via thromboelastometry

To assess the effects of in vitro hemodilution of canine blood with a low molecular weight hy-droxyethyl starch (HES 130/0.4) by means of thromboelastometry (TEM). In vitro experimental study. University Teaching Hospital. Ten healthy adult staff-owned dogs were sampled for the purposes of the study. Samples were also collected from 45 clinically normal dogs to establish thromboelastometric reference intervals. For each dog whole blood was collected by jugular venipuncture and placed into tubes containing 3.8% trisodium citrate and stored at 37°C. Two standard dilutions (1:4 and 1:10) from canine blood specimens were prepared with HES 130/0.4 and saline 0.9%. The effects of dilution were studied by TEM. No statistically significant differences were observed between the TEM values of the control samples and the samples diluted with saline solution (ratio 1:10 and 1:4). In contrast, hypocoagulability was observed in the samples treated with HES 130/0.4, with more severe effects at 1:4 dilution than at 1:10 dilution. The 1:4 dilution with HES 130/0.4 produced marked alterations: CT (P = 0.035) and CFT (P = 0.0007) on the ex-TEM profile, CT (P = 0.0005) and ML (P = 0.0017) on the fib-TEM profile and CFT (P = 0.0043) on the in-TEM, were all significantly increased (P < 0.05), whereas MCF (P = 0.0042) and alpha angle (P = 0.002) on the in-TEM and MCF (P = 0.011) and alpha angle (P = 0.001) ex-TEM profiles and MCF (P = 0.0001) on the fib-TEM profile were significantly decreased (P < 0.05). Dilution of canine blood with HES 130/0.4 results in a thromboelastometric pattern consistent with hypocoagulation and this effect appears to result from a dose-dependent alteration in fibrinogen concentration and inhibition of platelet function. As this is an in vitro study, further in vivo investigations are necessary to confirm the results.

Utility of interim ROTEM® values of clot strength, A5 and A10, in predicting final assessment of coagulation status in severely injured battle patients

BackgroundProactive management of trauma-related coagulopathy requires early identification and rapid assessment in order to allow targeted resuscitation. This study determined whether early (interim) ROTEM® (TEM International GmbH, Munich, Germany) values could predict hypocoagulopathy in seriously injured military patients. MethodsNormal ranges for ROTEM® values were obtained from 50 volunteers. 108 samples were collected during the early phase of clinical management from 48 severe trauma patients. The blood was subject to EXTEM analysis and compared to the 95% tolerance limits from the volunteers. Coagulopathy (was deemed to be present if EXTEM MCF was below 40mm, which is in the range indicating clinical concern defined by the ROTEM® Expert Working Group. ResultsThe normal range data was broadly similar to ROTEM® published data. Admission samples were available from 31 battlefield casualties, and 39% of these were coagulopathic 51% of the samples from all 48 patients were coagulopathic (EXTEM MCF<40mm) and interim EXTEM values of these at 5 and 10min (A5 and A10) predicted coagulopathy with sensitivities/specificities of 0.96/0.58 (A5) and 1.00/0.70 (A10).In addition, statistical comparison of clotting domains between normal volunteers and trauma patients suggests a difference in clot strengths due to a difference in platelet function rather than platelet number (mean 142×109l−1). ConclusionsThe A10 value of ROTEM® provides an early sensitive and specific assessment of coagulopathy after military trauma and may be of utility in guiding bespoke resuscitation. We found some speculative evidence that in major trauma platelet function is particularly affected.

Temporal changes in ROTEM®-measured coagulability of citrated blood samples from coagulopathic trauma patients

BackgroundRotational thromboelastometry (ROTEM®) relies on citrated blood samples, which are regarded as biologically stable for up to 4h after venepuncture. However, this recommendation is based on data from normal volunteers. The aim of this study was to evaluate possible temporal changes in the coagulability of blood samples from coagulopathic trauma patients. Patients and methodsThis is a prospective series of 10 coagulopathic (maximum clot firmness, MCF<40mm) trauma patients. ROTEM® EXTEM (tissue factor activated) and FIBTEM (tissue factor activated, cytochalasin D inhibited) analyses were performed on samples obtained on admission, and after approximately 60min of storage in an incubator, at 37°C. ResultsThere were statistically significant differences between the median EXTEM MCF (22mm vs 54mm, p<0.001) and α angle (30.5 vs 59.5°, p=0.004) of the analyses performed immediately after sampling, and 51min (median) subsequently, but not coagulation time (CT, p=0.133), clot formation time (p=0.0625) or maximum lysis (ML, p=0.154). There were also no differences in median FIBTEM MCF (p=1.00) or CT (p=0.877) between the immediate and delayed analyses. ConclusionsRepeated ROTEM® EXTEM analysis of citrated samples from coagulopathic trauma patients shows a spontaneous improvement in coagulability with time. The absence of parallel changes on FIBTEM analysis suggests that this effect may be due to a change in platelet function.

The In Vitro Effects of Fibrinogen Concentrate, Factor XIII and Fresh Frozen Plasma on Impaired Clot Formation After 60% Dilution

Previous investigations have shown that increasing fibrinogen concentration improves dilution-dependent impairment of clot formation. We conducted an in vitro study to explore whether substitution with fibrin-stabilizing factor XIII (FXIII) combined with fibrinogen promotes further improvement of clot formation, and whether fibrinogen administration as concentrate or fresh frozen plasma (FFP) results in comparable effects. Blood from six healthy donors was diluted by 60% using lactated Ringer's solution. Aliquots of diluted blood samples were incubated with two different doses of fibrinogen concentrate, FXIII concentrate, the combination of both, or with two different doses of FFP. Using thrombelastometry (ROTEM) blood samples were analyzed at baseline (undiluted), after dilution and after supplementation. Variables were analyzed for changes from baseline, and effects of fibrinogen concentrate alone or combined with FXIII were compared with effects observed with corresponding FFP doses. After 60% in vitro dilution of blood all ROTEM parameters and global coagulation tests changed significantly. Among the substitutes tested FXIII alone had no effect, the combination with fibrinogen improved coagulation time, alpha angle and fibrinogen/fibrin polymerization significantly more than did small-dose fibrinogen alone. After substituting fibrinogen, median values of all ROTEM variables were within the normal range, thereby showing dose dependency but also significant differences (P = 0.027) from corresponding FFP doses (EXTEM MCF FFP small dose [38 (35, 40.3) mm)], which enabled only coagulation time to be shortened to baseline levels. Supplementation of fibrinogen restored all ROTEM parameters after dilution. This effect was partially enhanced by adding FXIII and was significantly stronger than for FFP substitution.