Which Septic Shock Patients With Non-Overt DIC Progress to DIC After Admission? Point-of-Care Thromboelastography Testing.

BACKGROUND: Disseminated intravascular coagulation (DIC) is a life-threatening complication of septic shock; however, risk factors for its development after admission are unknown. Thromboelastography (TEG) can reflect coagulation disturbances in early non-overt DIC that are not detected by standard coagulation tests. This study investigated the risk factors including TEG findings as early predictors for DIC development after admission in septic shock patients with non-overt DIC. METHODS: This retrospective observation study included 295 consecutive septic shock patients with non-overt DIC at admission between January 2016 and December 2019. DIC was defined as an International Society on Thrombosis and Hemostasis (ISTH) score ≥ 5. The primary outcome was non-overt DIC at admission that met the ISTH DIC criteria within 3 days after admission. RESULTS: Of the 295 patients with non-overt DIC, 89 (30.2%) developed DIC after admission. The DIC group showed a higher ISTH score and 28-day mortality rate than the non-DIC group (2 vs. 3, P < 0.001; 13.6% vs. 27.0%, P = 0.008, respectively). The DIC rate increased with the ISTH score (7.7%, 13.3%, 15.8%, 36.5%, and 61.4% for scores of 0, 1, 2, 3, and 4, respectively). Among TEG values, the maximum amplitude (MA) was higher in the non-DIC group (P < 0.001). On multivariate analysis, an MA < 64 mm was independently associated with DIC development (odds ratio, 2.311; 95% confidence interval, 1.298-4.115). CONCLUSIONS: DIC more often developed among those with admission ISTH scores ≥ 3 and was associated with higher mortality rates. An MA < 64 mm was independently associated with DIC development in septic shock patients.

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.

Injury Severity, Arrival Physiology, Coagulopathy, and Outcomes Among the Youngest Trauma Patients.

BACKGROUND: Although physiologic differences exist between younger and older children, pediatric trauma analyses are weighted toward older patients. Trauma-induced coagulopathy, determined by rapid thrombelastography (rTEG), is a predictor of outcome in trauma patients, but the significance of rTEG values among very young trauma patients remains unknown. Our objective was to identify the prehospital or physiologic factors, including rTEG values, that were associated with mortality in trauma patients younger than 5 y old. MATERIALS AND METHODS: Patients younger than 5 y old that met the highest-level trauma activation criteria at an academic children's hospital from 2010-2016 were included. Data regarding demographics, pre-hospital management, laboratory values, injury severity, and outcome were queried. Univariate and multivariate analyses were performed comparing survivors and non-survivors. RESULTS: A total of 356 patients were included. 60% were male, and the median age was 3 y (IQR 1-4). Overall mortality was 13% (n = 45); brain injury (91%) and hemorrhage (9%) were the causes of death. Compared to survivors, rTEG values in nonsurvivors showed longer activated clotting time and slower speed of clot formation. Clot strength was also decreased in nonsurvivors. On stepwise regression modeling, rTEG values were not significant predictors of mortality. Admission base deficit, arrival temperature, and head injury severity were identified as independent predictors of mortality. CONCLUSIONS: While rTEG identified coagulopathy in trauma patients < 5 y old, it was not an independent predictor of mortality. Our findings suggest that trauma providers should pay close attention to admission base deficit, arrival temperature, and head injury severity when managing the youngest trauma patients.

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.

Coagulopathy, Bleeding Events, and Outcome According to Rotational Thromboelastometry in Patients With Acute Liver Injury/Failure.

BACKGROUND AND AIMS: Patients with acute liver injury or failure (ALI/ALF) experience bleeding complications uncommonly despite an abnormal hemostatic profile. Rotational thromboelastometry (ROTEM), which assesses clot formation in whole blood, was used to determine the nature of abnormal hemostasis and whether it contributes to bleeding events, illness severity, or survival. APPROACH AND RESULTS: A total of 200 patients were recruited from sites of the ALF Study Group. Blood collected daily for up to 5 days was analyzed using ROTEM delta devices. Consistent with standard laboratory evidence of hypocoagulability (median international normalized ratio = 2.9 and platelet count = 144 × 109 /L), patients frequently exhibited ROTEM parameters outside the normal range (73% and 62% had abnormalities in clot formation from extrinsic and intrinsic clotting cascades, respectively); however, measures of clot stability were generally normal. Eighteen patients (9%) experienced bleeding events, in whom clot initiation, assembly, and firmness were more severely deranged than patients without bleeding. Abnormal ROTEM parameters were more frequently observed in patients with non-acetaminophen ALI/ALF than those with acetaminophen ALI/ALF (clot initiation [P < 0.001], assembly [P = 0.02], firmness at 10 minutes [P = 0.05], and maximal firmness [P = 0.06]). Patients with more severe systemic complications (high-grade hepatic encephalopathy and need for renal replacement therapy) also had a higher incidence of abnormal ROTEM parameters. Finally, more hypocoagulable ROTEM parameters (clot initiation (P = 0.005), stiffness at 10 minutes (P = 0.05), and maximal stiffness by fibrin assembly (P = 0.004)) were observed in patients who died or underwent liver transplantation than those who survived with their native liver. CONCLUSIONS: In patients with ALI/ALF, abnormal ROTEM parameters are frequent and proportional to disease severity. Whether the increased bleeding risk associated with abnormal ROTEM indicates hemostatic failure or is a proxy for disease severity requires additional 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.

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.

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.

Assessment of hemostatic profile in patients with mild to advanced liver cirrhosis.

BACKGROUND: Hemostasis of patients suffering from liver cirrhosis is challenging due to both, pro- and anticoagulatory disorders leading to hemostatic alterations with distinct abnormalities of coagulation. Pathological changes in conventional coagulation analysis and platelet count are common manifestations of decreased liver synthesis of coagulation factors and reduced platelet count in these patients. However, conventional coagulation analysis and platelet count do not reflect in-vivo coagulation status or platelet function. The purpose of this present observational study was therefore to assess the haemostatic profile including plasmatic coagulation using thrombelastometry and impedance aggregometry for platelet function in patients suffering from liver cirrhosis. AIM: To assess the hemostatic profile of cirrhotic patients according to model for end-stage liver disease (MELD) score. METHODS: Our study included both in- and outpatients suffering from liver cirrhosis attending the out- and inpatient care of the department of hepatology. Demographic and biochemical data as well as medical history including cause of liver cirrhosis, end stage kidney failure and medication with anticoagulants were recorded. To assess the hemostatic profile, platelet function was analyzed by multiple electrode aggregometry (MEA) using Multiplate® (ADP-, ASPI- and TRAP-test) and thrombelastometry using ROTEM® (EXTEM, INTEM, FIBTEM). Data were compared using Mann-Whitney U- or χ 2-test. Spearman correlation was performed to analyze the association between MELD Score and results of thrombelastometry and MEA. RESULTS: A total of 68 patients attending the out- and inpatient care suffering from liver cirrhosis were screened. Of these, 50 patients were included and assigned to groups according to MELD score 6 to 11 (n = 25) or ≥ 17 (n = 25). Baseline patient characteristics revealed significant differences for MELD score (8 vs 22, P < 0.0001) and underlying laboratory parameters (international normalized ratio, bilirubine, creatinine) as well as fibrinogen level (275 mg/dL vs 209 mg/dL, P = 0.006) and aPTT (30 s vs 35 s, P = 0.047). MEA showed a moderately impaired platelet function (medians: AUCADP = 43U, AUCASPI = 71U, AUCTRAP = 92U) but no significant differences between both groups. Thrombelastometry using ROTEM® (EXTEM, INTEM, FIBTEM) revealed values within normal range in both groups. No significant correlation was observed between MELD score and results of MEA/thrombelastometry. CONCLUSION: Our data demonstrate a partially impaired hemostatic profile in liver cirrhosis patients unrelated to MELD score. An individual assessment of a potential coagulopathy should therefore be considered.

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.

Baseline parameters for rotational thromboelastometry in healthy labouring women: a prospective observational study.

OBJECTIVE: The aim of this study was to establish rotational thromboelastometry (ROTEM® ) baseline parameters in labouring women at term gestation. The secondary aim was to compare these reference ranges with those from previous studies on labouring women and from the manufacturer. DESIGN: A prospective, observational study. SETTING: Tertiary referral hospital. PARTICIPANTS: Healthy women in labour. METHODS: Ethics approval was granted for an opt-out recruitment approach. ROTEM® testing was performed in labouring women at term gestation. Women with any condition affecting coagulation were excluded. ROTEM® Delta reference ranges were derived by calculating the 2.5% and 97.5% centiles for INTEM/EXTEM/FIBTEM parameters including amplitude at 5 minutes (A5), coagulation time (CT) and maximum clot firmness (MCF). MAIN OUTCOME MEASURES: ROTEM® parameters were measured in labouring women before delivery. The following tests were performed: FIBTEM, EXTEM and INTEM. RESULTS: One hundred and twenty-one women met the inclusion criteria, with a mean (± SD) age of 29.6 ± 5.4 years and median (interquartile range) gestation of 39.4 weeks (37.4-40.4 weeks). Seventy-five (62.0%) women were nulliparous and 71 (58.7%) delivered vaginally. The median and interquartile ranges for selected ROTEM® parameters were: FIBTEM A5, 21 mm (IQR 18-23 mm); EXTEM A5, 55 mm (52-58 mm); and EXTEM CT, 52 seconds (48-56 seconds). CONCLUSIONS: The FIBTEM/EXTEM/INTEM amplitudes were higher than the manufacturer's reference ranges for non-obstetric patients. The FIBTEM MCF upper and lower limits were higher and the EXTEM/INTEM CT was shorter and narrower in range. This study provides reference ranges for ROTEM® values in healthy labouring women at term gestation with uncomplicated pregnancies. TWEETABLE ABSTRACT: This is the first study to report on ROTEM® reference ranges with over 120 healthy labouring women of normal weight at term gestation.

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.

Baseline parameters for rotational thromboelastometry (ROTEM®) in healthy women undergoing elective caesarean delivery: a prospective observational study in Australia.

BACKGROUND: Formal reference ranges for rotational thromboelastometry (ROTEM®) in pregnancy have not been obtained in the recommended minimum sample size of 120. This prospective observational study aimed to establish baseline parameters in an Australian population of women undergoing elective caesarean delivery. The secondary aim was to compare these reference ranges with those from prior studies and the manufacturer. METHODS: Women undergoing elective caesarean delivery at term were included if they were at term, of normal body mass index and had no conditions affecting coagulation. ROTEM® reference ranges were derived by calculating the 2.5 and 97.5 percentiles for INTEM/EXTEM/FIBTEM amplitude at 5 minutes (A5), amplitude at 15 minutes (A15), coagulation time (CT), maximum clot firmness (MCF), and clot formation time (CFT). RESULTS: Of 202 women screened, 132 met the inclusion criteria, having a mean age of 32.7 ±â€¯5.0 years and median body mass index of 23.8 kg/m2 (interquartile range 21.5-26.4). The reference ranges for selected ROTEM® parameters were as follows: FIBTEM A5 (13-28 mm), FIBTEM CT (40-74 s), FIBTEM MCF (16-34 mm), EXTEM A5 (39-66 mm), EXTEM CT (43-69 s), INTEM A5 (38-63 mm). CONCLUSIONS: ROTEM® reference ranges for women with uncomplicated term pregnancies were reported as per the International Federation of Clinical Chemistry. The FIBTEM MCF and FIBTEM/EXTEM/INTEM amplitudes were higher in comparison to the manufacturer's reference ranges for the non-obstetric population. The EXTEM CT was shorter than the non-obstetric reference ranges. These ranges show an increase in coagulability during normal pregnancy compared to the non-pregnant reference ranges.

An audit of the diagnostic accuracy of rotational thromboelastometry for the identification of hypofibrinogenaemia and thrombocytopenia during cardiopulmonary bypass.

We audited the diagnostic accuracy of ROTEM® (TEM Innovations, GmbH, Munich, Germany) measurements of hypofibrinogenaemia (fibrinogen <1.5 g/l) and thrombocytopenia (platelet count <100 x 109/l) in 200 adult non-transplant patients during cardiopulmonary bypass (CPB). Blood samples were obtained for FIBTEM (assay for the fibrin part of the clot), PLTEM (calculated platelet-specific component), and laboratory measurements simultaneously. Our thresholds for FIBTEM and PLTEM were A10 (clot firmness 10 minutes after clotting time) ≤8 mm, and <35 mm respectively. We also calculated the accuracy of smaller thresholds and earlier indices. We found that FIBTEM A10 ≤8 mm had low sensitivity (0.62) for hypofibrinogenaemia. With the 13% hypofibrinogenaemia prevalence in our sample, the positive predictive value (PPV) was 0.47. In contrast, FIBTEM A10 ≤8 mm had higher specificity (0.90) (negative predictive value [NPV] 0.94). Of the other FIBTEM values analysed, only A5 ≤6 mm had similar or superior accuracy. The PLTEM results were less encouraging (sensitivity 0.81, specificity 0.62). With our prevalence of thrombocytopenia (also 13%), the PPV was only 0.24. However, the NPV was high (0.96). Of the other PLTEM values analysed, only A5 <25 mm had similar or superior accuracy. These findings indicate that during CPB FIBTEM A10 ≤8 mm and PLTEM A10 <35 mm have greater accuracy in identifying the absence of hypofibrinogenaemia and thrombocytopenia respectively than their presence. On the basis of these results we would be reassured by FIBTEM A10 values >8 mm and PLTEM A10 values ≥35 mm, but would continue to use laboratory measurements for confirmation. We would not use FIBTEM A10 ≤8 mm or PLTEM A10 <35 mm values alone to guide replacement therapy unless clinical conditions warranted an immediate decision before laboratory measurements were available.

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.

Use of Thromboelastography to Predict Thrombotic Complications in Pediatric and Neonatal Extracorporeal Membranous Oxygenation.

The objectives of this study were to investigate the correlation between thromboelastography (TEG) and conventional measures of anticoagulation, and to determine optimum values for citrated kaolin TEG R time (TEG RCK) and anti-Xa activity that would minimize both bleeding and thrombotic complications in pediatric and neonatal patients requiring extracorporeal membranous oxygenation (ECMO). A retrospective chart review of patients requiring veno-venous (VV) and venoarterial (VA) ECMO was performed. Combined medical and cardiac ICU within a single-center, tertiary care, freestanding, children's hospital. Non-pregnant patients <18 years and >2 kilograms requiring VV or VA ECMO from July 2013 through July 2015. Anti-Xa (OR = 0.62, 95% CI 0.53-0.72, p < .001) and TEG RCK (OR = 1.19, 95% CI 1.07-1.34, p = .003) were the only independent predictors for a significant thrombotic event. Receiver operating characteristic curves and traditional epidemiological data (sensitivity, specificity, PPV, NPV) were used to determine optimal target Anti-Xa and TEG RCK values. No independent predictors for significant bleeding events were identified in this cohort. A anti-Xa activity of .25 IU/mL (sensitivity = 81%, specificity = 67%, PPV = 81%, NPV = 58%) and TEG RCK time of 17.85 minutes (sensitivity = 84%, specificity = 68%, PPV = 82%, NPV = 59%) were established as the optimal thresholds for preventing thrombotic events. Anti-Xa and TEG RCK were independent predictors of thrombosis in this cohort of pediatric and neonatal ECMO patients. Targeting an anti-Xa activity greater than .25 IU/mL and a TEG RCK greater than 17.85 minutes may minimize the risk of thrombosis in pediatric and neonatal ECMO patients. Future investigation should evaluate targets for anti-Xa and TEG RCK, which additionally minimize the risk of significant bleeding in this patient population.

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.