Thromboelastography with platelet mapping: Limited predictive ability in detecting preinjury antiplatelet agent use.

BACKGROUND: Preinjury antiplatelet agent (APA) use in trauma patients can increase traumatic hemorrhage and worsen outcomes. Thromboelastography with platelet mapping (TEGPM) has characterized platelet function via arachidonic acid (AA) and adenosine diphosphate (ADP) inhibition in nontrauma settings, but limited data exist in the acute trauma population. METHODS: A prospective observational study of adult trauma patients with suspected preinjury APA use who received TEGPM testing from 2017 to 2020 was performed. Patients on anticoagulants were excluded. Patients were grouped according to preinjury APA regimen: 81 mg or 325 mg of aspirin daily, 81 mg of aspirin and 75 mg of clopidrogrel daily, 75 mg of clopidrogrel daily, or no antiplatelet. Ability of TEGPM to detect APA use was assessed using predictive statistics and area under receiver operating characteristic curves (AUROCs). RESULTS: A total of 824 patients were included with most patients taking 81 mg of aspirin (n = 558). Patients on no antiplatelet were younger and had higher baseline platelet counts, while patients on 75 mg of clopidrogrel were more likely to be admitted after ground level fall. All other baseline characteristics were balanced. Admission TEG values were similar between groups. Median AA inhibition was higher in patients on aspirin containing regimens (p < 0.0001). Median ADP inhibition was higher in patients on clopidogrel containing regimens and those taking 325 mg of aspirin (p < 0.0001). Arachidonic acid inhibition accurately detected preinjury APA use and aspirin use (AUROC, 0.89 and 0.84, respectively); however, ADP inhibition performed poorly (AUROC, 0.58). Neither AA nor ADP inhibition was able to discern specific APA regimens or rule out APA use entirely. CONCLUSION: High AA inhibition accurately detects preinjury APA use in trauma patients. High ADP inhibition after trauma is common, limiting its utility to accurately identify preinjury APA use. Further study is needed to identify assays that can reliably detect and further characterize preinjury APA use in trauma populations. LEVEL OF EVIDENCE: Diagnostic test, level II.

Rotational Thromboelastometry Findings Are Associated with Symptomatic Venous Thromboembolic Complications after Hip Fracture Surgery.

BACKGROUND: Venous thromboembolism is a common complication after hip fractures. However, there are no reliable laboratory assays to identify patients at risk for venous thromboembolic (VTE) events after major orthopaedic surgery. QUESTION/PURPOSES: (1) Are rotational thromboelastometry (ROTEM) findings associated with the presence or development of symptomatic VTE after hip fracture surgery? (2) Were any other patient factors associated with the presence or development of symptomatic VTE after hip fracture surgery? (3) Which ROTEM parameters were the most accurate in terms of detecting the association of hypercoagulability with symptomatic VTE? METHODS: This retrospective study was conducted over a 13-month period. In all, 354 patients with femoral neck and peritrochanteric fractures who underwent hip hemiarthoplasty or cephallomedullary nailing were assessed for eligibility. Of those, 99% (349 of 354) were considered eligible for the study, 1% (3 of 354) of patients were excluded due to coagulation disorders, and another 1% (2 of 354) were excluded because they died before the postoperative ROTEM analysis. An additional 4% (13 of 354) of patients were lost before the minimum study follow-up of 3 months, leaving 95% (336 of 354) for analysis. A ROTEM analysis was performed in all patients at the time of their hospital admission, within hours of the injury, and on the second postoperative day. The patients were monitored for the development of symptoms indicative of VTE, and the gold standard tests for diagnosing VTE, such as CT pulmonary angiography or vascular ultrasound, were selectively performed only in symptomatic patients and not routinely in all patients. Therefore, this study evaluates the association of ROTEM with only clinically evident VTE events and not with all VTE events. ROTEM results did not affect the clinical surveillance of the study group and the decision for further work up. To determine whether ROTEM findings were associated with the presence or development of symptomatic VTE, ROTEM parameters were compared between patients with and without symptomatic VTE. To establish whether any other patient factors were associated with the presence or development of symptomatic VTE after hip fracture surgery, clinical parameters and conventional laboratory values were also compared between patients with and without symptomatic VTE. Finally, to determine which ROTEM parameters were the most accurate in terms of detecting the association of hypercoagulability with symptomatic VTE, the area under the curve (AUC) for certain cut off values of ROTEM parameters was calculated. RESULTS: We found several abnormal ROTEM values to be associated with the presence or development of symptomatic VTE. The preoperative maximum clot firmness was higher in patients with clinically evident VTE than in patients without these complications (median [interquartile range] 70 mm [68 to 71] versus 65 mm [61 to 68]; p < 0.001). The preoperative clot formation time was lower in patients with clinically evident VTE than those without clinically evident VTE (median 61 seconds [58 to 65] versus 70 seconds [67 to 74]; p < 0.001), and also the postoperative clot formation time was lower in patients with clinically evident VTE than those without these complications (median 52 seconds [49 to 59] versus 62 seconds [57 to 68]; p < 0.001). Increased BMI was also associated with clinically evident VTE (odds ratio 1.26 [95% confidence interval 1.07 to 1.53]; p < 0.001). We found no differences between patients with and without clinically evident VTE in terms of age, sex, smoking status, comorbidities, and preoperative use of anticoagulants. Lastly, preoperative clot formation time demonstrated the best performance for detecting the association of hypercoagulability with symptomatic VTE (AUC 0.89 [95% CI 0.81 to 0.97]), with 81% (95% CI 48% to 97%) sensitivity and 86% (95% CI 81% to 89%) specificity for clot formation time ≤ 65 seconds. CONCLUSION: ROTEM's performance in this preliminary study was promising in terms of its association with symptomatic VTE. This study extended our earlier work by demonstrating that ROTEM has a high accuracy in detecting the level of hypercoagulability that is associated with symptomatic VTE. However, until its performance is validated in a study that applies a diagnostic gold standard (such as venography, duplex/Doppler, or chest CT) in all patients having ROTEM to confirm its performance, ROTEM should not be used as a regular part of clinical practice. LEVEL OF EVIDENCE: Level IV, diagnostic study.

Trigger and Target for Fibrinogen Supplementation Using Thromboelastometry (ROTEM) in Patients Undergoing Open Thoraco-Abdominal Aortic Aneurysm Repair.

OBJECTIVE: To determine the relationship between the value of fibrinogen assessed by the FIBTEM clot amplitude at 10 minutes (A10 FIBTEM) measured on admission to the intensive care unit (ICU) and the amount of drainage output at 24 hours, to investigate whether the A10 FIBTEM predicts severe bleeding (SB), and to define A10 FIBTEM thresholds to prevent (trigger) and treat (target) severe bleeding by fibrinogen supplementation. METHODS: In a single centre, retrospective observational study, 166 patients underwent elective open thoraco-abdominal aortic aneurysm (TAAA) repair between March 2016 and January 2019. Exclusion criteria were emergency, congenital, or acquired coagulopathy, or administration of P2Y12 inhibitor antiplatelet agents in the five days before surgery. All patients were managed intra-operatively and post-operatively according to a rotational thromboelastometry driven transfusion protocol. The principal endpoint was a composite outcome, which included bleeding, large volume transfusion, and re-operation. RESULTS: FIBTEM clot amplitude after 10 minutes measured on ICU admission and post-operative bleeding at 24 hours showed an inverse linear relationship (R2 = .03; p = .026). Performance of A10 FIBTEM in predicting SB evaluated by Receiving Operating Curve analysis showed an area under the curve of 0.63 (95% CI 0.56 - 0.70; p = .026) with a best cutoff of 9 mm. An A10 FIBTEM of 3 mm was the cutoff associated with a positive predictive value of 50%, while an A10 FIBTEM of 9 mm showed a negative predictive value of 92%. On multivariable analysis, an A10 FIBTEM ≤ 3 mm remained independently associated with SB. CONCLUSION: The present investigation shows for the first time in a population undergoing open TAAA repair that an A10 FIBTEM ≤ 3mm on ICU admission is associated with post-operative severe bleeding. Trigger and target values for fibrinogen supplementation, based on A10 FIBTEM, have been provided. The transferability and reliability of these cutoff values require further study.

Thromboelastography findings in critically ill COVID-19 patients.

The rate of venous and arterial thrombotic events among patients infected with severe acute respiratory syndrome coronavirus-2 (SAR-CoV-2) is high. This may be due to a hypercoagulable state induced by the severe inflammation that results from the SAR-CoV-2 infection. We aimed to determine hypercoagulable states' incidence based on thromboelastography study and its association with thrombotic events in critically ill patients with coronavirus disease 2019 (COVID-19). Fifty-two COVID-19 patients who had thromboelastography study were retrospectively included. All patients received pharmacologic thromboprophylaxis. The hypercoagulable state was observed in 16 patients (30.8%). Among them, maximum amplitude and a-angle were elevated in 75% and 25%, respectively. Reaction time and K were low in only 12.5% for both of them. Inflammatory and coagulation markers, as well as thromboprophylaxis regimens, were not associated with a hypercoagulable state. Fourteen patients (27%) experienced a total of 16 thrombotic events, including 8 (57%) deep venous thrombosis, 6 (43%) pulmonary embolism, and 2 (14.3%) arterial thrombosis. The hypercoagulable state was not significantly associated with thrombotic events. In summary, we observed a lower rate of hypercoagulable state on thromboelastography study in critically ill COVID-19 patients. Also, the hypercoagulable state was not associated with the occurrence of thrombotic events.

Utility of rotational thromboelastometry in total hip replacement revision surgery (case-control study).

ABSTRACT: Total hip replacement revision surgery is accompanied by significant blood loss. Using rotational thrombelastometry (ROTEM) perioperatively to diagnose coagulopathy may help to provide rapid aimed therapy and thus decrease blood loss and the consumption of transfusion products. The aim of this case-control study was to find out whether point of care using of ROTEM may reduce blood loss and the consumption of blood transfusion products in hip replacement revision surgery.Data were prospectively collected from patients who underwent hip replacement revision surgery in the period 2017 to 2018 when the management of bleeding and coagulopathy was based on the results of ROTEM. Data were compared with a group of historical controls for the period 2015 to 2016 when bleeding and coagulopathy management was not based on ROTEM results. The consumption of blood transfusion products and perioperative blood loss were compared between the groups.The total number of analyzed patients was 90. Forty five patients were analyzed in the ROTEM group and the same number of patients were analyzed in the non-ROTEM group. Significantly decreased perioperative consumption of fresh frozen plasma and packed red blood cells was found in the ROTEM, as well as decreased perioperative blood loss comparing to non-ROTEM group. All data were statistically different with P < .05.Perioperative management of bleeding and coagulopathy based on the results of ROTEM during hip replacement revision surgery seems to help to decrease perioperative blood loss and the consumption of blood transfusion products, especially fresh frozen plasma.

Implementing thrombelastography: Experiences from a level I trauma institution.

Viscoelastic hemostatic assays such as thrombelastography (TEG) and rotational thrombelastometry have proven to be important point-of-care tools in the management of acute traumatic hemorrhage. Despite the availability of prospective studies that have confirmed the utility of TEG in reducing transfusion requirements and mortality in bleeding patients when compared to conventional coagulation tests, many institutions run into barriers implementing these viscoelastic hemostatic assays due to concerns regarding cost and benefit. At our academic Level 1 trauma institution, the Division of Trauma, Critical Care, and Acute Care Surgery advocated for the addition of TEG to the clinical armamentarium of providers caring for injured patients and thus spearheaded the clinical implementation of TEG. With the approval of the central laboratory, the Division developed an extensive and well-trained team to run and interpret TEGs as well as perform machine validation and upkeep. The Division continues to perform point-of-care testing throughout the hospital today.

Tranexamic acid administration in the field does not affect admission thromboelastography after traumatic brain injury.

BACKGROUND: No Food and Drug Administration-approved medication improves outcomes following traumatic brain injury (TBI). A forthcoming clinical trial that evaluated the effects of two prehospital tranexamic acid (TXA) dosing strategies compared with placebo demonstrated no differences in thromboelastography (TEG) values. We proposed to explore the impact of TXA on markers of coagulation and fibrinolysis in patients with moderate to severe TBI. METHODS: Data were extracted from a placebo-controlled clinical trial in which patients 15 years or older with TBI (Glasgow Coma Scale, 3-12) and systolic blood pressure of ≥90 mm Hg were randomized prehospital to receive placebo bolus/placebo infusion (placebo), 1 g of TXA bolus/1 g of TXA infusion (bolus maintenance), or 2 g of TXA bolus/placebo infusion (bolus only). Thromboelastography was performed, and coagulation measures including prothrombin time, activated partial thromboplastin time, international ratio, fibrinogen, D-dimer, plasmin-antiplasmin (PAP), thrombin antithrombin, tissue plasminogen activator, and plasminogen activator inhibitor 1 were quantified at admission and 6 hours later. RESULTS: Of 966 patients receiving study drug, 700 had laboratory tests drawn at admission and 6 hours later. There were no statistically significant differences in TEG values, including LY30, between groups (p > 0.05). No differences between prothrombin time, activated partial thromboplastin time, international ratio, fibrinogen, thrombin antithrombin, tissue plasminogen activator, and plasminogen activator inhibitor 1 were demonstrated across treatment groups. Concentrations of D-dimer in TXA treatment groups were less than placebo at 6 hours (p < 0.001). Concentrations of PAP in TXA treatment groups were less than placebo on admission (p < 0.001) and 6 hours (p = 0.02). No differences in D-dimer and PAP were observed between bolus maintenance and bolus only. CONCLUSION: While D-dimer and PAP levels reflect a lower degree of fibrinolysis following prehospital administration of TXA when compared with placebo in a large prehospital trial of patients with TBI, TEG obtained on admission and 6 hours later did not demonstrate any differences in fibrinolysis between the two TXA dosing regimens and placebo. LEVEL OF EVIDENCE: Diagnostic test, level III.

Accelerating availability of clinically-relevant parameter estimates from thromboelastogram point-of-care device.

BACKGROUND: Modeling approaches offer a novel way to detect and predict coagulopathy in trauma patients. A dynamic model, built and tested on thromboelastogram (TEG) data, was used to generate a virtual library of over 160,000 simulated RapidTEGs. The patient-specific parameters are the initial platelet count, platelet activation rate, thrombus growth rate, and lysis rate (P(0), k1, k2, and k3, respectively). METHODS: Patient data from both STAAMP (n = 182 patients) and PAMPer (n = 111 patients) clinical trials were collected. A total of 873 RapidTEGs were analyzed. One hundred sixteen TEGs indicated maximum amplitude (MA) below normal and 466 TEGs indicated lysis percent above normal. Each patient's TEG response was compared against the virtual library of TEGs to determine library trajectories having the least sum-of-squared error versus the patient TEG up to each specified evaluation time ∈ (3, 4, 5, 7.5, 10, 15, 20 minutes). Using 10 nearest-neighbor trajectories, a logistic regression was performed to predict if the patient TEG indicated MA below normal (<50 mm), lysis percent 30 minutes after MA (LY30) greater than 3%, and/or blood transfusion need using the parameters from the dynamic model. RESULTS: The algorithm predicts abnormal MA values using the initial 3 minutes of RapidTEG data with a median area under the curve of 0.95, and improves with more data to 0.98 by 10 minutes. Prediction of future platelet and packed red blood cell transfusion based on parameters at 4 and 5 minutes, respectively, provides equivalent predictions to the traditional TEG parameters in significantly less time. Dynamic model parameters could not predict abnormal LY30 or future fresh-frozen plasma transfusion. CONCLUSION: This analysis could be incorporated into TEG software and workflow to quickly estimate if the MA would be below or above threshold value within the initial minutes following a TEG, along with an estimate of what blood products to have on hand. LEVEL OF EVIDENCE: Therapeutic/Care Management: Level IV.

Comparison of the Coagulation Profile of Adolescent Idiopathic Scoliosis Patients Undergoing Posterior Spinal Fusion With and Without Tranexamic Acid.

STUDY DESIGN: Prospective, observational cohort study. OBJECTIVE: To improve the understanding of coagulation and bleeding mechanisms during spinal deformity surgery. SUMMARY OF BACKGROUND DATA: Fibrinolysis is the mechanism of bleeding for adolescent idiopathic scoliosis undergoing posterior spinal fusion. Antifibrinolytics have become popular; however, literature to support their use remains mixed. The mechanism of action has not been demonstrated. METHODS: The coagulation profile of 88 adolescent idiopathic scoliosis patients undergoing posterior spinal fusion was analyzed. Standard coagulation laboratory investigations and thromboelastograms were drawn hourly through the case. Fifty-eight patients received no antifibrinolytic, whereas 30 patients received tranexamic acid by standardized protocol. The coagulation parameters, estimated blood loss, and transfusion requirements were compared in the two groups. RESULTS: The two cohorts had no differences in demographic or surgical characteristics. Mean age was 13.6 years, 83% were female, a mean of 11.1 levels were fused, and the mean duration of surgery was 209 minutes. The tranexamic acid cohort did not demonstrate a decrease in blood loss. The transfusion rate, however, dropped from 47% in the non-tranexamic acid cohort to 23% in the tranexamic acid cohort (p = .03). Standard coagulation parameters did not differ between the groups. Fibrinolysis was diminished in the tranexamic acid cohort as measured by a Fibrinolysis score (mean maximum value 2.0 without tranexamic acid vs. 0.7 with tranexamic acid, p < .0001) and the lysis percent at 30 minutes by thromboelastogram (elevated to 3.9% without tranexamic acid vs. 1.2% with tranexamic acid at the 3-hour mark, p = .05). CONCLUSIONS: This study provides confirmation of antifibrinolytic activity during posterior spinal fusion for adolescent idiopathic scoliosis. The presented data of fibrinolysis are proposed as standard measurements for future work on controlling blood loss during scoliosis surgery. LEVEL OF EVIDENCE: Level 2, prospective comparative study.

Prediction of bleeding by thromboelastography in ICU patients with haematological malignancy and severe sepsis.

: ICU patients with haematological malignancy have an increased risk of bleeding. Recently, global haemostatic methods such as thromboelastography (TEG) have gained impact in evaluating coagulation. The aim of this study was to observe whether TEG could predict bleeding in haematological ICU patients with severe sepsis. Post-hoc single-centre analysis of patients with haematological malignancy included in the Scandinavian Starch for Severe Sepsis/Septic Shock (6S) trial. Clinical characteristics, TEG measurements and details regarding bleeding complications were retrieved from the 6S database. The association between TEG and bleeding were analysed by Cox regression and receiver operating characteristic curves. A total of 202 patients with severe sepsis were admitted to the ICU of Rigshospitalet, Copenhagen and included in the 6S trial. Forty-one had haematological malignancy and were analysed in the current study. During ICU stay, 20 patients (49%) had bleeding complications and 13 (32%) patients bled within the first 5 ICU days. We observed no associations between TEG and subsequent bleeding in Cox regression models. TEG variables at baseline had low predictive value for bleeding. Baseline TEG variables did not add value in identifying patients with high risk of bleeding in ICU patients with haematological malignancy and severe sepsis.

Microfluidics contrasted to thrombelastography: perplexities in defining hypercoagulability.

BACKGROUND: Elevated clot strength (maximum amplitude [MA]) measured by thrombelastography (TEG) is associated with thrombotic complications. However, it remains unclear how MA translates to thrombotic risks, as this measurement is independent of time, blood flow, and clot degradation. We hypothesize that under flow conditions, increased clot strength correlates to time-dependent measurements of coagulation and resistance to fibrinolysis. MATERIALS AND METHODS: Surgical patients at high risk of thrombotic complications were analyzed with TEG and total thrombus-formation analysis system (T-TAS). TEG hypercoagulability was defined as an r <10.2 min, angle >59, MA >66 or LY30 <0.2% (based off of healthy control data, n = 141). The T-TAS AR and PL chips were used to measure clotting at arterial shear rates. T-TAS measurements include occlusion start time, occlusion time (OT), occlusion speed (OSp), and total clot generation (area under the curve). These measurements were correlated to TEG indices (R time, angle, MA, and LY30). Both T-TAS and TEG assays were challenged with tissue plasminogen activator (t-PA) to assess clot resistance to fibrinolysis. RESULTS: Thirty subjects were analyzed, including five controls. TEG-defined hypercoagulability by MA was detected in 52% of the inflammatory bowel disease/cancer patients; 0% was detected in the controls. There were no TEG measurements that significantly correlated with T-TAS AR and PL chip. However, in the presence of t-PA, T-TAS AR determined OSp to have an inverse relationship with TEG angle (-0.477, P = 0.012) and LY30 (-0.449, P = 0.019), and a positive correlation with R time (0.441 P = 0.021). In hypercoagulability determined by TEG MA, T-TAS PL had a significantly reduced OT (4:07 versus 6:27 min, P = 0.043). In hypercoagulability defined by TEG LY30, T-TAS PL had discordant findings, with a significantly prolonged OT (6:36 versus 4:30 min, P = 0.044) and a slower OSp (10.5 versus 19.0 kPa/min, P = 0.030). CONCLUSIONS: Microfluidic coagulation assessment with T-TAS has an overall poor correlation with most TEG measurements in a predominantly hypercoagulable patient population, except in the presence of t-PA. The one anticipated finding was an elevated MA having a shorter time to platelet-mediated microfluidic occlusion, supporting the role of platelets and hypercoagulability. However, hypercoagulability defined by LY30 had opposing results in which a low LY30 was associated with a longer PL time to occlusion and slower OSp. These discordant findings warrant ongoing investigation into the relationship between clot strength and fibrinolysis under different flow conditions.

Prediction of Postoperative Blood Loss Using Thromboelastometry in Adult Cardiac Surgery: Cohort Study and Systematic Review.

OBJECTIVE: The aim was to evaluate the predictive value of thromboelastometry for postoperative blood loss in adult cardiac surgery with cardiopulmonary bypass. DESIGN: Retrospective cohort study and systematic review of the literature. SETTING: A tertiary university hospital. PARTICIPANTS: 202 patients undergoing elective cardiac surgery. INTERVENTIONS: Thromboelastometry was performed before cardiopulmonary bypass and 3 minutes after protamine administration. MEASUREMENTS AND MAIN RESULTS: The cohort study showed that the preoperative and postoperative thromboelastometric positive predicting value was poor (0%-22%); however, the negative predicting value was high (89%-94%). The systematic review of the literature to evaluate the predictive value of thromboelastometry for major postoperative bleeding in cardiac surgery resulted in 1,311 articles, 11 of which were eligible (n = 1,765; PubMed and Embase, until June 2016). Two studies found a good predictive value, whereas the other 9 studies showed a poor predictability for major postoperative bleeding after cardiac surgery. The overall negative predicting value was high. CONCLUSIONS: Thromboelastometry does not predict which patients are at risk for major postoperative bleeding.

Tranexamic acid leads to paradoxical coagulation changes during cardiac surgery: a pilot rotational thromboelastometry study.

BACKGROUND: Tranexamic acid (TXA) is increasingly used during major surgery with the goal to reduce excessive bleeding, transfusion requirements, and reexploration. Our aim was to examine the effect of TXA on coagulation at different times during cardiac surgery using rotational thromboelastometry. MATERIALS AND METHODS: Nineteen adult males (EuroSCORE 4-5) were recruited consecutively for first-time cardiopulmonary bypass (CPB) surgery. Ten patients received TXA at anesthesia and nine received no TXA. Rotational thromboelastometry analysis occurred before anesthesia (baseline), after sternotomy, after CPB-heparinization and surgery, and after protamine administration-sternal closure. RESULTS: A median sternotomy had no effect on clot time (CT), formation, amplitude, or lysis in non-TXA patients. In contrast, TXA patients had twofold prolonged clotting time (all-tests) and ∼30% reduced FIBTEM (A5-30) and maximum clot firmness, indicating reduced thrombin generation and lower clot fibrinogen. After CPB, CTs in both groups were prolonged, possibly linked to overheparinization. In addition, TXA patients had significantly decreased EXTEM (A5-30), suggesting lower clot strength. After protamine-sternal closure, clotting time remained prolonged in both groups, and TXA patients had a persistently 25%-33% lower FIBTEM (A5-30) and maximum clot firmness. TXA patients also had significantly reduced platelet numbers (37% from baseline), which continued Days 1 and 2. Maximum clot lysis was <10% indicating little or no hyperfibrinolysis during cardiac surgery. CONCLUSIONS: In this nonrandomized, nonblinded, observational trial, patients in the TXA group displayed prolonged CTs and clot fibrinogen (FIBTEM A5-30) after sternotomy, decreased clot strength (EXTEM) after CPB/surgery, and acute thrombocytopenia after protamine-sternal closure. There was no significant decrease in clot lysis, questioning the need for TXA in this medium-risk group.

A pilot study on the applicability of thromboelastometry in detecting brain tumour-induced hypercoagulation.

Patients with intracranial tumours have an increased risk of venous thromboembolism, particularly during the first month after neurosurgery. A proposed explanation for this increased risk, are procoagulant tumour-derived substances, such as tissue factor, usually measured in peripheral blood. The aim of the present study is to investigate whether a rotational thromboelastometry (ROTEM) can measure the procoagulative activity of tumour tissue. The study included 21 patients who were undergoing a craniotomy and complete tumour resection after written consent and ethical approval were obtained. Tumour tissue was biopsied during surgery and used for in vitro spiking of patients own citrated whole blood. Blood samples with or without spiking were analyzed with ROTEM using different activating reagents. ROTEM clotting time significantly decreased (p < .001), indicating a hypercoagulative response on clot initiation that was strongest for glioma tumours. However, ROTEM clot formation time was significantly prolonged (p < .001), which was an opposite response that indicated poor initial clot propagation. ROTEM maximum lysis was increased in the tumour tissue-spiked samples (p < .001), indicating a strong fibrinolytic activity in brain tumour tissue. Tissue extracts from intracranial tumours have both procoagulant and fibrinolytic effects that are detectable with ROTEM. Glioma tumours had the strongest hypercoagulative response in our in vitro model. Larger studies are necessary to test the clinical relevance and accuracy of tumour extract spiked viscoelastic tests to predict the individual patient risk for developing a thrombotic complication.

Kaolin-activated thromboelastography and standard coagulation assays in cyanotic and acyanotic infants undergoing complex cardiac surgery: a prospective cohort study.

BACKGROUND AND AIMS: Several studies report the use of thromboelatography (TEG) to monitor coagulation in pediatric cardiac surgery. The aim of this study was to compare baseline and intraoperative TEG, TEG-functional fibrinogen, and standard coagulation assays in children with cyanotic and acyanotic congenital heart disease (CHD) undergoing cardiac surgery. METHODS: This is a prospective observational study of 63 children aged <24 months undergoing cardiac surgery with cardiopulmonary bypass (CPB). Exclusion criteria included preoperative anticoagulant therapy and hepatic failure. We collected blood at anesthesia induction (T1), at lowest temperature after CPB start (T2), and after heparin neutralization (T3). Coagulation was evaluated by TEG (reaction time [R]), k, alpha-angle, maximum amplitude (MA), MA-fibrinogen (MA-fib), and by standard coagulation assays (prothrombin time, activated partial thromboplastin time, fibrinogen level, platelet [PLT] count). RESULTS: Sixty-three patients were enrolled (38 cyanotic and 25 acyanotic). Median age was 4 [IQR 2-6] months and median weight was 5 [IQR 3.7-6.5] kg. Most common surgeries were: ventricular septal defect repair (n = 13), Fallot correction (n = 11), and arterial switch operation (n = 10). Cyanotic and acyanotic children were well matched: R, k, MA, and MA-fib at T1, T2, and T3 were not significantly different between cyanotic and acyanotic children. At T2, significant correlations were showed between MA and PLT count (r = 0.4; P = 0.0008) and k and plasma fibrinogen level (r = -0.54; P < 0.0001). At T3, significant correlations were showed between MA and PLT count (r = 0.5; P < 0.0001), G and PLT count (r = 0.6; P < 0.0001), and MA-fib and plasma fibrinogen level (r = 0.5; P = 0.002). CONCLUSIONS: According to our findings, cyanosis does not affect TEG parameters in children with CHD. PLT count and plasma fibrinogen significantly correlated (are significantly associated) with MA and MA-fib respectively, suggesting that use of TEG after protamine administration may be prompted for improved hemostatic monitoring in the perioperative phase.

Practical Use of Thromboelastometry in the Management of Perioperative Coagulopathy and Bleeding.

Achieving hemostasis after complex cardiovascular and transplant surgical procedures is one of the greatest challenges anesthesiologists face. Preoperative coagulation disturbances due to underlying disease or antithrombotic therapy are common, and they are worsened by intraoperative blood loss and fluid replacement. The coagulation reactions in vivo are incredibly complex interactions among blood cells, proteins, and vasculature, standing in sharp contrast to rather simple treatment options including transfusion of platelets, plasma, and cryoprecipitate. The long turnaround time of laboratory coagulation testing, and intraoperative heparin use also make timely coagulation assessment difficult during cardiopulmonary bypass, and thus, hemostatic components are often empirically ordered and administered without knowing their actual need or efficacy. However, increasing clinical experience with viscoelastic coagulation testing in cardiac and transplant anesthesia has introduced a paradigm shift, enabling clinicians to obtain clinically relevant coagulation data in a timely fashion and to treat a specific element of coagulation that is dysfunctional. Viscoelastic coagulation testing may facilitate an optimal use of blood components and other hemostatic agents, but its application is often practice specific (ie, type of surgery), and there are technical limitations and learning curves. The aims of this review are thus to summarize recent clinical data on viscoelastic coagulation testing and to provide practical examples of its use in complex cardiac surgical and transplant cases.

Equiosmolar Solutions of Hypertonic Saline and Mannitol Do Not Impair Blood Coagulation During Elective Intracranial Surgery.

BACKGROUND: The authors investigated the effect of equiosmolar, equivolemic solutions of 3% hypertonic saline (HS) and 20% mannitol on blood coagulation assessed by rotational thromboelastometry (ROTEM) and standard coagulation tests during elective craniotomy. METHODS: In a prospective, randomized, double-blind trial, 40 patients undergoing elective craniotomy were randomized to receive 5 mL/kg of either 20% mannitol or 3% HS for intraoperative brain relaxation. Fibrinogen, activated partial thromboplastin time, prothrombin time, hemoglobin, hematocrit, and platelet count were simultaneously measured intraoperatively with ROTEM for EXTEM, INTEM, and FIBTEM analysis. ROTEM parameters were: clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), and α-angle. RESULTS: No significant differences between groups were found in ROTEM variables CT, CFT, MCF, α-angle (EXTEM and INTEM), and MCF (FIBTEM) nor standard coagulation tests. ROTEM parameters did not show changes after administration of hyperosmolar solutions relating to basal values, except for an increase of CFT EXTEM (118±28 vs. 128±26 s) and decrease of CT INTEM (160±18 vs. 148±15 s) with values within normal range. Significant decreases from baseline levels were observed for hematocrit (-7%), platelet count (-10%), and fibrinogen (-13%) after HS infusion, and hematocrit (-9%), platelet count (-13%), and fibrinogen (-9%) after mannitol infusion, but remaining normal. CONCLUSIONS: The use of 5 mL/kg of equiosmolar solutions of 3% HS and 20% mannitol applied to reach a brain relaxation during elective craniotomy does not induce coagulation impairment as evidenced by ROTEM and standard coagulation tests.

Predictive Value of Intraoperative Thromboelastometry for the Risk of Perioperative Excessive Blood Loss in Infants and Children Undergoing Congenital Cardiac Surgery: A Retrospective Analysis.

OBJECTIVE: Laboratory hemostatic variables and parameters of rotational thromboelastometry (ROTEM) were evaluated for their ability to predict perioperative excessive blood loss (PEBL) after congenital cardiac surgery. DESIGN: Retrospective and observational. SETTING: Single, large university hospital. PARTICIPANTS: The study comprised 119 children younger than 10 years old undergoing congenital cardiac surgery with cardiopulmonary bypass (CPB). MEASUREMENTS AND MAIN RESULTS: Intraoperative excessive blood loss was defined as estimated blood loss≥50% of estimated blood volume (EBV). Postoperative excessive blood loss was defined as measured postoperative chest tube and Jackson-Pratt drainage≥30% of EBV over 12 hours or≥50% of EBV over 24 hours in the intensive care unit. PEBL was defined as either intraoperative or postoperative excessive blood loss. External temogram (EXTEM) and fibrinogen temogram (FIBTEM) were analyzed before and after CPB with ROTEM and laboratory hemostatic variables. Multivariate logistic regression was performed. Incidence of PEBL was 19.3% (n = 23). Independent risk factors for PEBL were CPB time>120 minutes, post-CPB FIBTEM alpha-angle, clot firmness after 10 minutes<5 mm, post-CPB EXTEM alpha-angle, clot firmness after 10 minutes<30 mm, and post-CPB EXTEM maximal lysis>20%. Laboratory hemostatic variables were not significant in multivariate analysis. The risk prediction model was developed from the results of multivariate analysis. The area under the receiver operating characteristic curve was 0.94 (95% confidence interval: 0.90-0.99). CONCLUSIONS: Post-CPB ROTEM may be useful for predicting both intraoperative and postoperative excessive blood loss in congenital cardiac surgery. This study provided an accurate prediction model for PEBL and supported intraoperative transfusion guidance using post-CPB FIBTEM-A10 and EXTEM-A10.

Perioperative coagulation assessment of patients undergoing major elective orthopedic surgery.

Traditional coagulative parameters are of limited use in identifying perioperative coagulopathy occurring in patients undergoing major elective orthopedic surgery (MEOS). The aim of our study was to evaluate the coagulation changes in patients undergoing MEOS and to facilitate an early detection of perioperative coagulopathy in patients experiencing major intraoperative bleeding. We enrolled 40 consecutive patients (M/F 10/30, age range 34-90 years) who underwent MEOS at the Orthopedic Unit of the Padua University Hospital, Italy, between January 2014 and January 2015. Blood samples were obtained at the following time points: T0-pre: 30 min before surgery; T0-post: 30 min after the end of the procedure; T1: morning of the first postoperative day; T2: 7 ± 2 days after surgery. Patients who experienced an intraoperative blood loss ≥250 mL/h were considered as cases. Routine coagulative parameters, thromboelastometry and thrombin generation (TG) profiles were evaluated. At baseline, a significantly lower platelet count and FIBTEM MCF/AUC were observed in patents with excessive bleeding (p < 0.05 and 0.02/0.01, respectively). At T0-post and T1 intervals, cases showed hypocoagulation characterized by a significantly low platelet count (p = 0.001), prolonged CFT INTEM/EXTEM, reduction of alpha-angle and MaxV INTEM/EXTEM, MCF and AUC INTEM/EXTEM/FIBTEM (p < 0.05 in all comparisons). The only TG parameter standing out between study groups was time to peak at T0-pre. A low platelet count and fibrinogen activity were associated with significant intraoperative bleeding in patients undergoing MEOS. Thromboelastometry performed by ROTEM(®) identifies patients with coagulopathy.

Thromboelastometry versus free-oscillation rheometry and enoxaparin versus tinzaparin: an in-vitro study comparing two viscoelastic haemostatic tests' dose-responses to two low molecular weight heparins at the time of withdrawing epidural catheters from ten patients after major surgery.

BACKGROUND: Monitoring low molecular weight heparins (LMWH's) in the perioperative period is prudent in patients at high risk of coagulative complications, especially when the patient has an epidural catheter requiring withdrawal, which is associated with the risk of spinal haematoma. The aim of this study was to evaluate the in vitro dose-responses of two different LMWH's on two different viscoelastic haemostatic tests, using blood sampled from patients with normal routine coagulation parameters, on the day after major surgery when their epidural catheters were due to be withdrawn. METHODS: Enoxaparin or tinzaparin were added in vitro to blood from ten patients who had undergone oesophageal resection, to obtain plasma concentrations of approximately 0, 0.5, 1.0 and 1.5 IU/mL. Coagulation was monitored using thromboelastometry (ROTEM®) using the InTEM® activating reagent; and free oscillation rheometry (FOR: ReoRox®), activated using thromboplastin. Clot initiation was measured using ROTEM-CT, ReoRox-COT1 and ReoRox-COT2. Clot propagation was measured using ROTEM-CFT, ROTEM-Alpha Angle and ReoRox-Slope. Clot stability was measured using ROTEM-MCF and ReoRox-G'max, and clot lysis was measured using ROTEM-ML and ReoRox-ClotSR. RESULTS: Clot initiation time assessed by thromboelastometry and FOR was prolonged by increasing concentrations of both LMWH's (P < 0.01). Equivalent doses of tinzaparin in international units (anti-FXa units) per millilitre prolonged clot initiation more than enoxaparin (P < 0.05). There was significant inter-individual variation - the ranges of CT and COT1 at LMWH-concentrations of 0 and 1.5 IU/mL overlapped. None of the tests reflecting clot formation rate or stability showed a dose-response to either LMWH but clot lysis showed a tentative negative dose-response to the LMWH's. CONCLUSIONS: Clot initiation time's dose-dependent prolongation by LMWH's in this study agrees with previous research, as does tinzaparin's stronger anti-coagulative effect than enoxaparin at equivalent levels of anti-FXa activity. This casts doubt on the validity of using anti-FXa assays alone to guide dosage of LMWH's. The significant inter-individual variation in dose-response suggests that the relationship between dose and effect in the postoperative period is complicated. While both ROTEM and FOR may have some role in postoperative monitoring, more research is needed before any conclusion can be made about their clinical usefulness.