A comparative evaluation of rotation thromboelastometry and standard coagulation tests in hemodilution-induced coagulation changes after cardiac surgery

BACKGROUND: Coagulopathy after cardiopulmonary bypass (CPB) is caused by multiple perturbations in cellular and humoral elements of coagulation. A timely and comprehensive method to evaluate hemostasis would be helpful in the management of bleeding patients after CPB. The assessment of whole blood coagulation using rotation thromboelastometry (ROTEM) was compared to coagulation tests routinely performed during cardiac surgery. STUDY DESIGN AND METHODS: Blood was obtained from 26 patients undergoing CPB surgery at baseline, at 60 minutes on CPB, at the end of CPB, and on admission to intensive care unit. ROTEM tests (extrinsically activated [EXTEM], intrinsically activated [INTEM], specific clot formation [FIBTEM]), prothrombin time, activated partial thromboplastin time, platelet (PLT) count, fibrinogen, prothrombin level, antithrombin level, and thrombin generation (TG) measurement were performed. RESULTS: We observed strong correlations between FIBTEM‐amplitude at 10 minutes (A10) and fibrinogen level (r = 0.87; p < 0.001) and between EXTEM/ INTEM‐A10 variables and PLT count (r = 0.72 and 0.67, respectively; p < 0.001). Receiver operating characteristic analysis demonstrated that EXTEM‐A10 and INTEM‐A10 are predictive of thrombocytopenia below 80 × 10⁹/L (area under the curve [AUC], 0.83 and 0.82, respectively), and FIBTEM‐A10 was highly predictive of fibrinogen level below 200 mg/dL (AUC, 0.96). There were only weak correlations found between TG peak and clot formation time of EXTEM or INTEM (r = 0.30 and 0.29, respectively; p < 0.05). CONCLUSION: ROTEM variables demonstrated clinically relevant correlations with PLT counts and fibrinogen levels. In particular, decreasing levels of fibrinogen can be quickly determined (<15‐20 min) using FIBTEM.     

Warfarin monitoring with viscoelastic haemostatic assays,thrombin generation,coagulation factors and correlations to Owren and Quick prothrombin time

The anticoagulant warfarin is commonly monitored with prothrombin time (PT). Viscoelastic haemostatic assays (VHA) are primarily used in situations of acute bleeding to guide haemostatic therapy. Much research has focused on VHA monitoring of new oral anticoagulants. However, many patients are still anticoagulated with warfarin and effect of warfarin anticoagulation on VHA is uncertain. The aim of this study was to assess warfarin anticoagulation on three different VHA and compare these findings with prothrombin time (PT), coagulation factor analyses and a thrombin generation assay (TGA). Citrated whole blood was drawn from 80 patients admitted for routine PT-INR Owren. VHA analysis with ROTEM (EXTEM, INTEM and FIBTEM), ReoRox (Fibscreen 1 and 2) and Sonoclot (gbACT+) was performed. Blood was also drawn for plasma analysis with PT (PT-INR Owren and PT Quick), TGA and analysis of factors I, II, VII, IX and X. Extrinsically activated VHA, including ROTEM EXTEM and FIBTEM Clotting Time (CT) and ReoRox Fibscreen1 and 2 clot onset time 1 correlated moderately with PT-INR Owren , with R 0.66–0.71. These four variables were likely to be prolonged above reference interval in patients with prolonged PT-INR Owren >1.2. Two patients with normal ROTEM CTs had Owren PT-INRs >1.5. Warfarin affects extrinsically activated VHA variables of initial clotting. The role of VHA for clinical decision-making in patients planned for invasive procedures, such as spinal/epidural anaesthesia needs further study. None of the recent guidelines on regional anaesthesia include VHA testing to define adequate haemostasis.     

Rotational thromboelastometry predicts thromboembolic complications after major non-cardiac surgery

Introduction

Thromboembolic complications contribute substantially to perioperative morbidity and mortality. Routine laboratory tests do not detect patients with acquired or congenital hypercoagulability who may be at increased risk of perioperative thromboembolism. Rotational thromboelastometry (ROTEM) is a digitized modification of conventional thromboelastography that is stable and technically easy to use. We designed a prospective observational study to evaluate whether preoperative ROTEM can identify patients at increased risk for postoperative thromboembolic complications after major non-cardiac surgery.

Methods

Preoperative ROTEM analysis using extrinsic rotational thromboelastometry (EXTEM), intrinsic rotational thromboelastometry (INTEM), and fibrinogen rotational thromboelastometry (FIBTEM) activators was performed on 313 patients undergoing major non-cardiac surgery. Patients’ medical records were reviewed after discharge for results of standard coagulation studies - partial thromboplastin time (PTT), international normalized ratio (INR), platelet count - and evidence of thromboembolic complications during their hospital stay. A thromboembolic complication was defined as a new arterial or deep venous thrombosis, catheter thrombosis, or pulmonary embolism diagnosed by ultrasound or spiral chest computed tomography.

Results

Ten patients developed postoperative thromboembolic complications, of whom 9 had received standard prophylaxis with subcutaneous enoxaparin or heparin. There was no indication of by PTT, INR, or platelet count. Preoperative EXTEM and INTEM activators that assess fibrin clot formation and platelet interaction indicated that these patients had significantly lower clot formation time (CFT) and significantly higher alpha angle (α) and maximum clot firmness (MCF), compared to patients without thromboembolic complications. There was no significant difference for any parameter using FIBTEM activator, which excludes platelet interaction. Receiver operating characteristic (ROC) curves were constructed for these variables. INTEM clot firmness at 10 min (A10) was the best predictor of thromboembolic complications, with an ROC area under the curve of 0.751.

Conclusions

Our results indicate that preoperative ROTEM assays that include fibrin clot and platelet interaction may detect patients at increased risk for postoperative thromboembolic complications after major non-cardiac surgery. Future studies need to evaluate the clinical utility and cost effectiveness of preoperative ROTEM and better define the association between ROTEM values and specific hypercoagulable conditions.     

Detection of acute traumatic coagulopathy and massive transfusion requirements by means of rotational thromboelastometry: an international prospective validation study

IntroductionThe purpose of this study was to re-evaluate the findings of a smaller cohort study on the functional definition and characteristics of acute traumatic coagulopathy (ATC). We also aimed to identify the threshold values for the most accurate identification of ATC and prediction of massive transfusion (MT) using rotational thromboelastometry (ROTEM) assays.MethodsIn this prospective international multicentre cohort study, adult trauma patients who met the local criteria for full trauma team activation from four major trauma centres were included. Blood was collected on arrival to the emergency department and analyzed with laboratory international normalized ratio (INR), fibrinogen concentration and two ROTEM assays (EXTEM and FIBTEM). ATC was defined as laboratory INR >1.2. Transfusion requirements of ≥10 units of packed red blood cells within 24 hours were defined as MT. Performance of the tests were evaluated by receiver operating characteristic curves, and calculation of area under the curve (AUC). Optimal cutoff points were estimated based on Youden index.ResultsIn total, 808 patients were included in the study. Among the ROTEM parameters, the largest AUCs were found for the clot amplitude (CA) 5 value in both the EXTEM and FIBTEM assays. EXTEM CA5 threshold value of ≤37 mm had a detection rate of 66.3% for ATC. An EXTEM CA5 threshold value of ≤40 mm predicted MT in 72.7%. FIBTEM CA5 threshold value of ≤8 mm detected ATC in 67.5%, and a FIBTEM CA5 threshold value ≤9 mm predicted MT in 77.5%. Fibrinogen concentration ≤1.6 g/L detected ATC in 73.6% and a fibrinogen concentration ≤1.90 g/L predicted MT in 77.8%. Patients with either an EXTEM or FIBTEM CA5 below the optimum detection threshold for ATC received significantly more packed red blood cells and plasma.ConclusionsThis study confirms previous findings of ROTEM CA5 as a valid marker for ATC and predictor for MT. With optimum threshold for EXTEM CA5 ≤ 40 mm and FIBTEM CA5 ≤ 9 mm, sensitivity is 72.7% and 77.5% respectively. Future investigations should evaluate the role of repeated viscoelastic testing in guiding haemostatic resuscitation in trauma.     

The effect of hypertonic saline and mannitol on coagulation in moderate traumatic brain injury patients

Background

Hyperosmolar therapy, using either hypertonic saline (HTS) or mannitol (MT), is considered the treatment of choice for intracranial hypertension, a disorder characterized by high intracranial pressure (ICP). However, hyperosmolar agents have been postulated to impair coagulation and platelet function. The aim of this study was to identify whether HTS and MT could affect coagulation in moderate traumatic brain injury (TBI) patients.

Diagnosis of early coagulation abnormalities in trauma patients by rotation thrombelastography

BACKGROUND: Reagent-supported thromboelastometry with the rotation thrombelastography (e.g. ROTEM) is a whole blood assay that evaluates the visco-elastic properties during blood clot formation and clot lysis. A hemostatic monitor capable of rapid and accurate detection of clinical coagulopathy within the resuscitation room could improve management of bleeding after trauma. OBJECTIVES: The goals of this study were to establish whether ROTEM correlated with standard coagulation parameters to rapidly detect bleeding disorders and whether it can help to guide transfusion. METHODS: Ninety trauma patients were included in the study. At admission, standard coagulation assays were performed and ROTEM parameters such as clot formation time (CFT) and clot amplitude (CA) were obtained at 15 min (CA(15)) with two activated tests (INTEM, EXTEM) and at 10 min (CA(10)) with a test analyzing specifically the fibrin component of coagulation (FIBTEM). RESULTS: Trauma induced significant modifications of coagulation as assessed by standard assays and ROTEM. A significant correlation was found between prothrombin time (PT) and CA(15)-EXTEM (r = 0.66, P < 0.0001), between activated partial thromboplastin time and CFT-INTEM (r = 0.91, P < 0.0001), between fibrinogen level and CA(10)-FIBTEM (r = 0.85, P < 0.0001), and between platelet count and CA(15)-INTEM (r = 0.57, P < 0.0001). A cutoff value of CA(15)-EXTEM at 32 mm and CA(10)-FIBTEM at 5 mm presented a good sensitivity (87% and 91%) and specificity (100% and 85%) to detect a PT > 1.5 of control value and a fibrinogen less than 1 g L(-1), respectively. CONCLUSIONS: ROTEM is a point-of-care device that rapidly detects systemic changes of in vivo coagulation in trauma patients, and it might be a helpful device in guiding transfusion.     

FIBTEM provides early prediction of massive transfusion in trauma

Introduction

Prediction of massive transfusion (MT) among trauma patients is difficult in the early phase of trauma management. Whole-blood thromboelastometry (ROTEM^®) tests provide immediate information about the coagulation status of acute bleeding trauma patients. We investigated their value for early prediction of MT.

Methods

This retrospective study included patients admitted to the AUVA Trauma Centre, Salzburg, Austria, with an injury severity score ≥16, from whom blood samples were taken immediately upon admission to the emergency room (ER). ROTEM^® analyses (extrinsically-activated test with tissue factor (EXTEM), intrinsically-activated test using ellagic acid (INTEM) and fibrin-based extrinsically activated test with tissue factor and the platelet inhibitor cytochalasin D (FIBTEM) tests) were performed. We divided patients into two groups: massive transfusion (MT, those who received ≥10 units red blood cell concentrate within 24 hours of admission) and non-MT (those who received 0 to 9 units).

Results

Of 323 patients included in this study (78.9% male; median age 44 years), 78 were included in the MT group and 245 in the non-MT group. The median injury severity score upon admission to the ER was significantly higher in the MT group than in the non-MT group (42 vs 27, P < 0.0001). EXTEM and INTEM clotting time and clot formation time were significantly prolonged and maximum clot firmness (MCF) was significantly lower in the MT group versus the non-MT group (P < 0.0001 for all comparisons). Of patients admitted with FIBTEM MCF 0 to 3 mm, 85% received MT. The best predictive values for MT were provided by hemoglobin and Quick value (area under receiver operating curve: 0.87 for both parameters). Similarly high predictive values were observed for FIBTEM MCF (0.84) and FIBTEM A10 (clot amplitude at 10 minutes; 0.83).

Conclusions

FIBTEM A10 and FIBTEM MCF provided similar predictive values for massive transfusion in trauma patients to the most predictive laboratory parameters. Prospective studies are needed to confirm these findings.     

Coagulation under Mild Hypothermia Assessed by Thromboelastometry

IntroductionWhile previous studies have shown a significant impact of extreme hypo- and hyperthermia on coagulation, effects of much more frequently occurring perioperative mild hypothermia are largely unknown. This study therefore aimed to analyze the effects of mild hypothermia using rotational thromboelastometry in vitro.Materials and MethodsTwelve healthy volunteers were included in this study. Standard thromboelastometric tests (EXTEM, INTEM, FIBTEM) were used to evaluate coagulation in vitro at 39, 37, 35.5, 35, and 33°C. Beyond standard thromboelastometric tests, we also evaluated the effects of mild hypothermia on the TPA-test (ClotPro, Enicor GmbH, Munich, Germany), a new test which aims to detect fibrinolytic capacity by adding tissue plasminogen activator to the sample. Data are presented as the median with 25/75th percentiles.ResultsExtrinsically activated coagulation (measured by EXTEM) showed a significant increase in clot formation time (CFT; 37°C: 90 s [81/105] vs. 35°C: 109 s [99/126]; p = 0.0002), while maximum clot firmness (MCF) was not significantly reduced. Intrinsically activated coagulation (measured by INTEM) also showed a significant increase in CFT (37°C: 80 s [72/88] vs. 35°C: 94 s [86/109]; p = 0.0002) without significant effects on MCF. Mild hypothermia significantly increased both the lysis onset time (136 s [132/151; 37°C] vs. 162 s [141/228; 35°C], p = 0.0223) and lysis time (208 s [184/297; 37°C] vs. 249 s [215/358; 35°C]; p = 0.0259).ConclusionThis demonstrates that even under mild hypothermia coagulation is significantly altered in vitro. Perioperative temperature monitoring and management are greatly important and can help to prevent mild hypothermia and its adverse effects. Further investigation and in vivo testing of coagulation under mild hypothermia is needed.     

Comparison of thromboelastometry by ROTEM® Delta and ROTEM® Sigma in women with postpartum haemorrhage

Haemostatic treatment in women experiencing postpartum haemorrhage is increasingly based on point-of-care devices such as ROTEM^® thromboelastometry. Recently, a fully automated successor of the ROTEM^® Delta device, the ROTEM^® Sigma was introduced. To determine whether these devices provide similar results, we compared ROTEM^® parameters using the ROTEM^® Delta and Sigma devices in women experiencing postpartum haemorrhage. Prospective observational cohort study of 23 women experiencing postpartum haemorrhage. ROTEM^® INTEM, EXTEM, FIBTEM and APTEM measurements handled by the ROTEM^® Delta and Sigma devices were compared. ROTEM^® FIBTEM values were also related to Clauss fibrinogen values. A correlation of Spearman’s r (r_s) varying between 0.76 and 0.95 was displayed between clot firmness measured in millimeters at 5 (A5), 10 (A10) and 20 (A20) minutes after start of clot formation measured by EXTEM, INTEM and APTEM assays executed on both devices; A5, A10 and A20 of FIBTEM correlated less well (r_S between 0.71 and 0.74), especially after five and ten minutes. Correlation between both devices regarding clotting time (CT) was poor. The observed correlation between levels of Clauss fibrinogen and FIBTEM A5 was r_s = 0.70, (95% confidence interval (CI): 0.38 to 0.87) for Delta and r_s = 0.85, (CI 0.65 to 0.94) for Sigma. A5, A10 and A20 measured in EXTEM, INTEM and APTEM obtained from ROTEM^® Delta and Sigma devices were similar. EXTEM, FIBTEM and APTEM CT values from both devices showed no correlation. Substantial variation was found between FIBTEM assays of the devices. Consequently, results of FIBTEM assays should always be interpreted in the context of device-specific reference values. Correlation with Clauss fibrinogen was better in the ROTEM^® Sigma device.     

Are thromboelastometric and thromboelastographic parameters associated with mortality in septic patients? A systematic review and meta-analysis

BackgroundThromboelastometry/elastography (ROTEM/TEG) showed promising results for diagnosis of sepsis-induced coagulopathy, but their association with the outcome is unclear. Our aim was to assess any difference in ROTEM/TEG measurements between septic survivors and non-survivors.MethodsPubmed, Web of Science, Embase and Cochrane Library databases were investigated. The research aimed to include any randomized or observational study: i) on septic adult patients admitted to Intensive Care Unit (ICU) or Emergency Department (ED); ii) including ROTEM/TEG; iii) assessing mortality.ResultsSeven prospective and four retrospective observational studies (952 patients) were included. According to the INTEM/kaolin-assay, clotting time (CT)/R (standardized mean difference(SMD) −0.29, 95% CI −0.49 to −0.09, p = 0.004) and clot formation time (CFT)/K (SMD −0.42, 95% CI −0.78 to −0.06, p = 0.02) were shorter in survivors. According to the EXTEM-assay, CT was shorter (MD −11.66 s, 95% CI −22.59 to −0.73, p = 0.04), while MCF was higher (MD 3.49 mm, 95% CI 0.43 to 6.55, p = 0.03) in survivors. A hypocoagulable profile was more frequent in non-survivors (OR 0.31, 95%CI 0.18 to 0.55, p < 0.0001). Overall, the risk of bias of the included studies was moderate and the quality of evidence low.ConclusionsHypocoagulability and lower MCF in EXTEM may be associated with higher mortality in sepsis.     

ROTEM in the setting of liver transplant surgery reduces frozen plasma transfusion

BackgroundINR is traditionally used as a marker of clinical coagulopathy, but is suboptimal in liver disease patients due to rebalanced hemostasis and its ineffectiveness to predict bleeding. Rotational thromboelastometry (ROTEM) testing evaluates whole blood hemostasis, which may provide more accurate assessments with the EXTEM CT parameter than INR. Thus, in end-stage liver disease (ESLD) patients, we hypothesized that elevated INRs are associated with normal EXTEM CT values.MethodsA retrospective study assessing adult (>18) patients with ESLD and elevated INRs undergoing liver transplantation, was performed to assess correlations between INR and EXTEM CT. This included patients post-ROTEM implementation where all had pre-operative ROTEM testing; and patients up to one year pre-ROTEM implementation to compare transfusion utilization. Data abstracted also included patient demographics, coagulation testing results, liver disease etiology, and MELD score.ResultsThe study included 138 patients in the post-ROTEM group and 59 patients in the pre-ROTEM group. Normal EXTEM CT was observed in 95.3 % and 93 % of patients with INR of 1.3–1.8 and up to 3 respectively. There was no correlation between INR of 1.3–1.8 and EXTEM CT (? = 0.239), and only moderate correlation was observed with higher INRs (? = 0.617 with INRs >1.8). ROTEM-guided transfusion in liver transplant surgeries was associated with reduced plasma transfusion (OR 0.27, 95 % CI 0.12?0.58, p = 0.001) after adjusting for red cell utilization and coagulation testing.ConclusionOur study suggests ROTEM may be advantageous for evaluating coagulopathy in patients with liver disease and ROTEM-guided transfusion reduces plasma transfusion.     

Hyperfibrinolysis is common in out-of-hospital cardiac arrest : Results from a prospective observational thromboelastometry study

Background

Cardiocirculatory arrest (CCA) activates procoagulant pathways. It has also been reported to inhibit fibrinolysis, resulting in fibrin deposition and further impairment of blood flow. Until now, no studies have used whole-blood viscoelastic tests to characterize coagulation and the impact of fibrinolysis in out-of-hospital cardiac arrest (OHCA).

Methods

Patient with established OHCA who underwent cardiopulmonary resuscitation (CPR) were enrolled. Blood samples were obtained immediately after placement of an intravenous line at the scene, for full blood cell count, standard coagulation tests and rotational thromboelastometric (ROTEM^®) analyses. Patients with return of spontaneous circulation (ROSC) were compared to non-ROSC patients.

Results

Fifty-three patients (median age 67 years, interquartile range: 56–73 years) were included in the study. ROSC was established in 25 patients. Prothrombin time index (PTI) was significantly lower and activated partial thromboplastin time (aPTT) was significantly prolonged in non-ROSC patients compared to ROSC patients. Clotting time (CT) in the extrinsically activated ROTEM test (EXTEM) was significantly longer in non-ROSC versus ROSC patients. For the remaining EXTEM parameters, there were no significant differences between ROSC and non-ROSC patients. Hyperfibrinolysis (maximum lysis > 15% according to ROTEM test results) was observed in 19 patients (35.8%). There was no difference between ROSC and non-ROSC patients in the incidence of hyperfibrinolysis.

Conclusions

PTI, aPTT and EXTEM CT revealed significant differences between ROSC and non-ROSC patients. Hyperfibrinolysis according to ROTEM test results was much more common than previously assumed. Routine use of fibrinolytic therapy in all patients with prolonged CPR cannot therefore be recommended.     

A comparison of fibrinogen measurement methods with fibrin clot elasticity assessed by thromboelastometry, before and after administration of fibrinogen concentrate in cardiac surgery patients

BACKGROUND: Fibrinogen concentrate administration can be guided by measuring fibrinogen concentration or quality of the fibrin‐based clot. This study compared different fibrinogen concentration measurement methods with maximum clot firmness (MCF) of the fibrin clot, assessed by thromboelastometry (FIBTEM), in 33 cardiovascular surgery patients receiving fibrinogen concentrate for hemostatic therapy. STUDY DESIGN AND METHODS: Blood samples were collected after cardiopulmonary bypass (CPB) and after fibrinogen concentrate administration. FIBTEM MCF was measured using a rotational thromboelastometry device (ROTEM, Tem International). Fibrinogen concentration was measured using photo‐optical (CA‐7000, Siemens Healthcare Diagnostics), mechanical (KC‐10 steel ball, Schnitger and Gross hook, Amelung GmbH), and electromechanical (STA‐R, Diagnostica Stago) coagulometers. Assessments included agreement between fibrinogen concentration measurements and correlations between fibrinogen concentration and FIBTEM MCF. RESULTS: After CPB, correlations were significant (p < 0.001) between FIBTEM MCF and fibrinogen concentration determined by steel ball (r = 0.71), hook (r = 0.73), STA‐R (r = 0.81), and CA‐7000 (r = 0.82) coagulometers. After fibrinogen concentrate administration, agreement between fibrinogen measurement methods was severely impaired, and correlations with FIBTEM MCF were 0.39 (steel ball), 0.33 (hook), 0.59 (STA‐R), and 0.33 (CA‐7000). CONCLUSION: Agreement between fibrinogen concentration measurement methods decreased considerably after fibrinogen concentrate administration. All methods correlated acceptably with FIBTEM MCF at the end of CPB, but not after hemostatic therapy. Further investigation is needed to explain these findings.     

Complete clinical course of envenomation by Protobothrops mangshanensis: delayed coagulopathy and response to Trimeresurus albolabris antivenom

Introduction: Protobothrops mangshanensis, the Mangshan pit viper, is a rare pit viper native to the area surrounding Mount Mang in China’s Hunan province. Toxicity from envenomation is not well characterized. Case details: A 33-year-old male presented to an emergency department (ED) after being bitten on the forearm by his P. mangshanensis. He complained of mild swelling and pain at the bite site. He was admitted for observation and toxicology consultation. Following initially normal coagulation studies including platelets, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and D-dimer, fibrinogen decreased to 121?mg/dL and D-dimer concurrently rose to 377?ng/mL over 24?h. On hospital day 2 fibrinogen stabilized at 109?mg/dL and he was discharged with outpatient laboratory monitoring. Three days later, he returned with bruising to the contralateral arm. Fibrinogen was undetectable (<40?mg/dL) and PT was 14.6?s. He declined admission but returned 2 d later with bruising to the nose. Bloodwork revealed immeasurably prolonged PT, aPTT, and thrombin time, but he eloped. Late that evening he returned and was treated with three vials of Green pit viper (Trimeresurus albolabris) antivenom. Within 24 h coagulopathy improved markedly; at five days, coagulation abnormalities resolved. Discussion: Mangshan pit viper envenomations may cause isolated hemotoxicity, despite molecular studies suggesting additional neurotoxicity and myotoxicity. T. albolabris antivenom appears effective in treating the resultant coagulopathy. Conclusion: We report the natural history of envenomation by the Mangshan pit viper. A delayed coagulopathy, apparently fibrinolytic in nature, is unaccompanied by local tissue destruction and responsive to Green pit viper antivenom.     

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?p??1 (SD 0.002?g L^?1) vs. 0.002?g L^?1 (SD 0.002?g L^?1; p?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.     

Reference intervals for coagulation tests in adults with different ABO blood types

IntroductionCoagulation tests are affected by many factors, such as age, race, and gestation. Although coagulation test results vary by ABO blood type, reference intervals of different ABO blood groups remain to be determined. This study aims to investigate the reference ranges of coagulation tests for different ABO blood groups in the Han population in South China.MethodsA retrospective study was conducted in the First Affiliated Hospital of Shantou University Medical College. In all, 9600 individuals aged between 20 and 79 years were included. Coagulation tests, including prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), thrombin time, and fibrinogen, were performed.ResultsThere was a significant difference in PT, INR, and aPTT among ABO blood groups. PT and INR varied slightly between ABO blood groups. There was a higher aPTT value in individuals in the O blood group than in those in non‐O blood groups, in both males and females across the included age range. No differences were found in thrombin time and fibrinogen between the ABO blood groups.ConclusionThe study provides reference data on coagulation tests from ABO blood groups in South China. The established reference intervals specific to ABO blood type, sex, and age may improve clinical decisions based on coagulation tests.     

Validation of rotation thrombelastography in a model of systemic activation of fibrinolysis and coagulation in humans

BACKGROUND: Thrombelastography (TEG) is a whole blood assay to evaluate the viscoelastic properties during blood clot formation and clot lysis. Rotation thrombelastography (e.g. ROTEM) has overcome some of the limitations of classical TEG and is used as a point-of-care device in several clinical settings of coagulation disorders. Endotoxemia leads to systemic activation of the coagulation system and fibrinolysis in humans. OBJECTIVES: We validated whether ROTEM is sensitive to endotoxin induced, tissue factor-triggered coagulation and fibrinolysis and if its measures correlate with biohumoral markers of coagulation and fibrinolysis. PATIENTS AND METHODS: Twenty healthy male volunteers participated in this randomized placebo-controlled trial. Volunteers received either 2 ng kg(-1) National Reference Endotoxin or saline. RESULTS: Endotoxemia significantly shortened ROTEM clotting time (CT) by 36% (CI 0.26-0.46; P < 0.05) with a strong inverse correlation with the peak plasma levels of prothrombin fragments (F(1 + 2)) (r = -0.83, P < 0.05). Additionally, endotoxin infusion enhanced maximal lysis (ML) 3.9-fold (CI: 2.5-5.2) compared with placebo or baseline after 2 h (P < 0.05). Peak ML and peak tissue plasminogen activator (t-PA) values correlated excellently (r = 0.82, P < 0.05). ROTEM parameters clot formation time and maximal clot firmness were not affected by LPS infusion, whereas platelet function analyzer (PFA-100) closure times decreased. CONCLUSIONS: Rotation thrombelastography (ROTEM) detects systemic changes of in vivo coagulation activation, and importantly it is a point of care device, which is sensitive to changes in fibrinolysis in humans. The ex vivo measures CT and ML correlate very well with established in vivo markers of coagulation activation (F(1 + 2)) and fibrinolysis (t-PA), respectively.     

Baseline haemoglobin and thromboelastometry are predictive of red blood cell requirements and one-year mortality in liver transplantation

BackgroundTo determine the predictive capacity of baseline haemoglobin and maxim clot firmness (MCF) EXTEM thromboelastometry for intraoperative red blood cell (RBC) requirements and its influence on mortality.Methods591 adult liver transplant (LT) recipients from ten Spanish centres were reviewed. The main outcomes were the percentage of patients who received RBC and massive transfusion (≥ 6 RBC units), RBC units transfused, and mortality.Results76 % received a donor after brain death graft and 24 % a controlled donor after circulatory death graft. Median (interquartile ranges) RBC transfusion was 2 (0–4) units, and 63 % of patients were transfused. Comparing transfused and non-transfused patients, mean (standard deviation) for baseline haemoglobin was 10.4 (2.1) vs. 13.0 (1.9) g/dl (p = 0.001), EXTEM MCF was 51(11) vs. 55(9) mm (p = 0.001). Haemoglobin and EXTEM MCF were inversely associated with the need of transfusion odds ratio (OR) of 0.558 (95 % CI 0.497–0.627, p < 0.001) and OR 0.966 (95 % CI0.945–0.987, p = 0.002), respectively. Pre-operative baseline haemoglobin ≤ 10 g/dL predicted RBC transfusion, sensitivity of 93 % and specificity of 47 %. Massive transfusion (MT) was received by 19 % of patients. Haemoglobin ≤10 g/dL predicted MT with sensitivity 73 % and specificity of 52 %. One-year patient and graft survival were significantly lower in patients who required MT (78 % and 76 %, respectively) vs. those who did not (94 % and 93 %, respectively).Discussionwhereas EXTEM MCF is less dreterminant predicting RBC requirements, efforts are required to improve preoperative haemoglobin up to 10 g/dl in patients awaiting LT.     

An assessment of thromboelastometry to monitor blood coagulation and guide transfusion support in liver transplantation

BACKGROUND: Rotation thromboelastometry (TEM) has been proposed as a convenient alternative to standard coagulation tests in guiding the treatment of coagulopathy during orthotopic liver transplantation (OLT). This study was aimed at assessing the value of TEM in monitoring blood coagulation and guide transfusion support in OLT. STUDY DESIGN AND METHODS: Standard coagulation and TEM (EXTEM and FIBTEM) tests were performed at four preestablished intraoperative time points in 236 OLTs and prospectively recorded in a dedicated database together with the main operative and transfusion data. Transfusion thresholds were based on standard coagulation tests. Spearman's rank correlation (ρ), linear regression, and receiver operating characteristic curves were used when appropriate. RESULTS: EXTEM maximum clot firmness (MCF_EXTEM) was the TEM variable that best correlated with the platelet (PLT) and fibrinogen levels (ρ = 0.62 and ρ = 0.69, respectively). MCF_FIBTEM correlated with fibrinogen level (ρ = 0.70). EXTEM clot amplitude at 10 minutes (A10_EXTEM) was a good linear predictor of MCF_EXTEM (R² = 0.93). The cutoff values that best predicted the transfusion threshold for PLTs and fibrinogen were A10_EXTEM = 35 mm and A10_FIBTEM = 8 mm. At these values, the negative and positive predictive accuracies of TEM to predict the transfusion thresholds were 95 and 27%, respectively. CONCLUSION: A10_EXTEM is an adequate TEM variable to guide therapeutic decisions during OLT. Patients with A10_EXTEM of greater than 35 mm are unlikely to bleed because of coagulation deficiencies, but using A10_EXTEM of not more than 35 mm as the sole transfusion criterion can lead to unnecessary utilization of PLTs and fibrinogen‐rich products.