Admission viscoelastic hemostatic assay parameters predict poor long-term intracerebral hemorrhage outcomes.

Background: Viscoelastic hemostatic assays (VHA) provide more comprehensive assessments of coagulation compared to conventional coagulation assays. While VHAs have enabled guided hemorrhage control therapies, improving clinical outcomes in life-threatening hemorrhage, the role of VHAs in intracerebral hemorrhage (ICH) is unclear. If VHAs can identify coagulation abnormalities relevant for ICH outcomes, this would support the need to investigate the role of VHAs in ICH treatment paradigms. Thus, we investigated whether VHA assessments of coagulation relate to long-term ICH outcomes. Methods: Spontaneous ICH patients enrolled into a single-center cohort study receiving admission Rotational Thromboelastometry (ROTEM) VHA testing between 2013 and 2020 were assessed. Patients with prior anticoagulant use or coagulopathy on conventional coagulation assays were excluded. Primary ROTEM exposure variables were coagulation kinetics and clot strength assessments. Poor long-term outcome was defined as modified Rankin Scale ≥ 4 at 6 months. Logistic regression analyses assessed associations of ROTEM parameters with clinical outcomes after adjusting for ICH severity and hemoglobin concentration. Results: Of 44 patients analyzed, mean age was 64, 57% were female, and the median ICH volume was 23 mL. Poor 6-month outcome was seen in 64%. In our multivariable regression models, slower, prolonged coagulation kinetics (adjusted OR for every second increase in clot formation time: 1.04, 95% CI: 1.00-1.09, p = 0.04) and weaker clot strength (adjusted OR for every millimeter increase of maximum clot firmness: 0.84, 95% CI: 0.71-0.99, p = 0.03) were separately associated with poor long-term outcomes. Conclusions: Slower, prolonged coagulation kinetics and weaker clot strength on admission VHA ROTEM testing, not attributable to anticoagulant use, were associated with poor long-term outcomes after ICH. Further work is needed to clarify the generalizability and the underlying mechanisms of these VHA findings to assess whether VHA guided treatments should be incorporated into ICH care.

Rotational Thromboelastometry as a Diagnostic Tool for Persistent Infection in Two-Stage Exchange Arthroplasty.

Background/Objectives: There is a lack of reliable biomarkers for diagnosis of infection eradication prior to second-stage reimplantation in two-stage exchange arthroplasty for periprosthetic joint infections (PJIs). The aim of this study was to assess the diagnostic accuracy of rotational thromboelastometry (ROTEM) for persistent infection in two-stage exchange arthroplasties. Methods: A pilot, retrospective analysis was performed including 70 patients who underwent a two-stage exchange arthroplasty for PJI. They were categorized as patients without (n = 64) or patients with persistent infection (n = 6) prior to reimplantation. Definition of persistent infection prior to reimplantation was based on the 2018 ICM criteria. Conventional coagulation biomarkers and ROTEM parameters were compared between groups. Results: Higher FIBTEM MCF values were associated with persistent infection (odds ratio [OR], 1.30, 95% confidence interval [CI], 1.04-1.63; p = 0.020), and FIBTEM MCF had the highest diagnostic accuracy for persistent infection prior to second-stage reimplantation (AUC, 0.907; 95% CI, 0.812-1.000). A cut-off value ≥ 18 mm for FIBTEM MCF was found to have 100.0% sensitivity and 73.4% specificity for diagnosing persistent infection prior to second-stage reimplantation. Moreover, the diagnostic accuracy of FIBTEM MCF was higher than that of fibrinogen levels (p = 0.036) and D-dimer (p = 0.006). Conclusions: Our findings indicate that ROTEM parameters have the potential to identify persistent infections before reimplantation in two-stage exchange arthroplasties for PJI. Such coagulation biomarkers could provide guidance regarding the optimal timing for reimplantation. Further studies in larger populations are warranted to validate the diagnostic accuracy of ROTEM parameters for persistent PJI.

Persistent hypofibrinolysis in severe COVID-19 associated with elevated fibrinolysis inhibitors activity.

Hypercoagulability and reduced fibrinolysis are well-established complications associated with COVID-19. However, the timelines for the onset and resolution of these complications remain unclear. The aim of this study was to evaluate, in a cohort of COVID-19 patients, changes in coagulation and fibrinolytic activity through ROTEM assay at different time points during the initial 30 days following the onset of symptoms in both mild and severe cases. Blood samples were collected at five intervals after symptoms onset: 6-10 days, 11-15 days, 16-20 days, 21-25 days, and 26-30 days. In addition, fibrinogen, plasminogen, PAI-1, and alpha 2-antiplasmin activities were determined. Out of 85 participants, 71% had mild COVID-19. Twenty uninfected individuals were evaluated as controls. ROTEM parameters showed a hypercoagulable state among mild COVID-19 patients beginning in the second week of symptoms onset, with a trend towards reversal after the third week of symptoms. In severe COVID-19 cases, hypercoagulability was observed since the first few days of symptoms, with a tendency towards reversal after the fourth week of symptoms onset. A hypofibrinolytic state was identified in severe COVID-19 patients from early stages and persisted even after 30 days of symptoms. Elevated activity of PAI-1 and alpha 2-antiplasmin was also detected in severe COVID-19 patients. In conclusion, both mild and severe cases of COVID-19 exhibited transient hypercoagulability, reverted by the end of the first month. However, severe COVID-19 cases sustain hypofibrinolysis throughout the course of the disease, which is associated with elevated activity of fibrinolysis inhibitors. Persistent hypofibrinolysis could contribute to long COVID-19 manifestations.

Association between loss of hypercoagulable phenotype, clinical features and complement pathway consumption in COVID-19.

Background: Coronavirus disease 2019 (COVID-19) features a hypercoagulable state, but therapeutic anticoagulation effectiveness varies with disease severity. We aimed to evaluate the dynamics of the coagulation profile and its association with COVID-19 severity, outcomes, and biomarker trajectories. Methods: This multicenter, prospective, observational study included patients with COVID-19 requiring respiratory support. Rotational thromboelastometry findings were evaluated for coagulation and fibrinolysis status. Hypercoagulable status was defined as supranormal range of maximum clot elasticity in an external pathway. Longitudinal laboratory parameters were collected to characterize the coagulation phenotype. Results: Of 166 patients, 90 (54%) were severely ill at inclusion (invasive mechanical ventilation, 84; extracorporeal membrane oxygenation, 6). Higher maximum elasticity (P=0.02) and lower maximum lysis in the external pathway (P=0.03) were observed in severely ill patients compared with the corresponding values in patients on non-invasive oxygen supplementation. Hypercoagulability components correlated with platelet and fibrinogen levels. Hypercoagulable phenotype was associated with favorable outcomes in severely ill patients, while normocoagulable phenotype was not (median time to recovery, 15 days vs. 27 days, P=0.002), but no significant association was observed in moderately ill patients. In patients with severe COVID-19, lower initial C3, minimum C3, CH50, and greater changes in CH50 were associated with the normocoagulable phenotype. Changes in complement components correlated with dynamics of coagulation markers, hematocrit, and alveolar injury markers. Conclusions: While hypercoagulable states become more evident with increasing severity of respiratory disease in patients with COVID-19, normocoagulable phenotype is associated with triggered by alternative pathway activation and poor outcomes.

Higher Doses of Calcium Associated With Survival in Trauma Patients.

INTRODUCTION: Calcium is required for coagulation, cardiac output, and peripheral vascular resistance. Between 85% and 94% of trauma patients treated with massive blood transfusion develop hypocalcemia.1 The aim of this study is to evaluate the relationship between increased intravenous calcium administration during massive transfusion and improved survival of trauma patients. METHODS: We performed a retrospective analysis of trauma patients who received massive transfusion over a 2-y period. Doses of elemental calcium administered per unit of blood product transfused were calculated by calcium to blood product ratio (CBR). Chi-square test evaluated association between coagulopathy and 30-d mortality. Two-sample t-test evaluated association between CBR and coagulopathy. Bivariate regression analysis evaluated association between CBR and blood products transfused per patient. Multivariable logistic regression analysis, controlling for age, sex, coagulopathy, and Injury Severity Score evaluated the association between CBR and mortality. RESULTS: The study included 77 patients. Coagulopathy was associated with increased 30-d mortality (P < 0.05). Patients who survived had higher CBR than those who died (P < 0.05). CBR was associated with a significant reduction in total blood products transfused per patient (P < 0.05). CBR was not associated with coagulopathy (P = 0.24). Multivariable logistic regression analysis demonstrated that Injury Severity Score ≥16, coagulopathy and decreased CBR were significant predictors of mortality (P < 0.05). CBR above 50 mg was a predictor of survival (P < 0.05). CONCLUSIONS: Higher doses of calcium given per blood product transfused were associated with improved 30-d survival and decreased blood product transfusions.

Thromboelastography versus thromboelastometry for unfractionated heparin monitoring in adult patients on extracorporeal membrane oxygenation.

Background: Monitoring the anticoagulant effect of unfractionated heparin (UFH) in extracorporeal membrane oxygenation (ECMO) patients is complex but critically important to balance the risks of treatment related bleeding and circuit thrombosis. While guidelines recommend using more than one method to monitor UFH activity, the use of thromboelastometry (ROTEM) to monitor UFH in ECMO patients has not been investigated in detail.Methods: This is an observational, single-center retrospective study looking at adult ECMO patients on UFH that had ROTEM and thromboelastography (TEG) tests obtained concurrently. A total of 20 samples were obtained from nine patients during the study period, seven of which were on veno-arterial (VA) ECMO and two of which were on veno-venous (VV) ECMO.Results: Under institutional standard operating practice, when TEG and/or activated partial thromboplastin time (aPTT) were considered therapeutic, intrinsic thromboelastometry clotting time (INTEM CT) was only 1.2 times higher than the normal range. TEG based monitoring compared to aPTT based monitoring tended to result in lower anti-Xa levels and less intensive anticoagulation. For the total cohort, bleeding events, driven by the need for blood transfusions, were more common compared to ischemic events (77% vs 11%; p = 0.02).Conclusion: INTEM CT tended to be less sensitive to lower doses of UFH with a value of 1.2 times higher than the normal range when aPTT and/or TEG were considered therapeutic. Due to the relative insensitivity of ROTEM, our institution decided to continue to use TEG instead of ROTEM. Larger, multicenter trials may be helpful to validate these findings.

Fibrinogen levels in severe trauma: A preliminary comparison of Clauss Fibrinogen, ROTEM Sigma, ROTEM Delta and TEG 6s assays from the FEISTY pilot randomised clinical trial.

OBJECTIVE: To describe the relationships between different methods of measuring functional fibrinogen levels in severely injured, bleeding trauma patients across multiple timepoints during hospitalisation. METHODS: In 100 adult trauma patients enrolled in the FEISTY pilot randomised clinical trial at four tertiary trauma centres in Australia, blood samples were collected prospectively. Consistency of agreement was calculated, comparing functional fibrinogen levels measured by four methods - ROTEM® Delta and Sigma FIBTEM A5, TEG® 6s CFF MA, and gold-standard Clauss Fibrinogen. RESULTS: Comparing the ROTEM® Delta and new-generation ROTEM® Sigma machine, consistency of agreement for FIBTEM A5, measured by calculating intraclass correlation coefficients (ICCs), was ≥0.73 across all analysed timepoints, with mean differences (Sigma minus Delta) of 0.10-3.57 mm. Corresponding values comparing the ROTEM® Sigma FIBTEM A5 and TEG® 6s CFF MA were ICC = 0.55-0.82 and ICC = 4.69-7.97 (CFF MA minus A5). Comparing ROTEM® Sigma FIBTEM A5 and Clauss Fibrinogen Analysis (CFA), among statistically significant simple linear regression models, R2 was 0.25-0.67, and comparing TEG® 6s CFF MA and CFA (CFA) 0.65-0.82, although not all differences were significant with the latter comparison. Relationships across all timepoints combined were Clauss Fibrinogen (CF) (g/L) = 0.21𝑥 + 0.004 (where 𝑥 = ROTEM® Sigma FIBTEM A5 in mm) and (g/L) = 0.16𝑥 - 0.06 (where 𝑥 = TEG® 6s CFF MA in mm). CONCLUSIONS: The present study revealed acceptable agreement between four different assays measuring functional fibrinogen, with current- and previous-generation ROTEM® machines (Sigma, Delta) performing similarly measuring functional fibrinogen via FIBTEM assay. This suggests that haemostatic resuscitation algorithms designed for the ROTEM® Delta can be applied to the ROTEM® Sigma to guide fibrinogen replacement.

Serial rotational thromboelastometry measurements show worsening hypocoagulability in acute-on-chronic liver failure and are associated with the severity of liver disease.

Background: Viscoelastic tests are used to better understand the complex picture of hemostasis in cirrhosis. Limited data exist regarding the clinical relevance of rotational thromboelastometry (ROTEM) in acute-on-chronic liver failure (ACLF) or acute decompensation (AD). We examined the pattern and role of sequential observations of 9 ROTEM components in both ACLF and AD groups. Method: ROTEM measurements were compared within and between groups at 3 time points: on admission (T1), at 24 h (T2) and 48 h post-admission (T3). Results: Forty-two consecutive patients (22 ACLF, 20 AD) were included. ROTEM determinants exhibited significant hypocoagulable deterioration in ACLF but not in AD over the 3 time points in clot formation time (CFT)EXTEM (P=0.01), maximum clot firmnessEXTEM (P=0.014), CFTINTEM (P<0.001), and alphaINTEM (P=0.028). The sum of hypocoagulable determinants increased from T1 to T3 in ACLF (P=0.029), but remained stable in AD. Five ROTEM variables showed significant differences towards hypocoagulability in ACLF compared to AD at T3. A "hypocoagulable" profile was associated with more severe liver disease (P<0.001 for model for end-stage liver disease [MELD] or Child-Pugh scores) and higher 30- and 90-day mortality (log-rank P=0.001 and P=0.013, respectively) but no more bleeding episodes or transfusions. Two ROTEM variables displayed strong correlations with MELD at T1 and 7 at T3 (|r coefficient|>0.5). Conclusions: ROTEM measurements indicated worsening hypocoagulability shortly post-admission compared to baseline in ACLF, but remained stable in AD. The hypocoagulable derangement was mostly correlated with the severity of liver disease and higher short-term mortality, but not more bleeding episodes.

User Perceptions of Visual Clot in a High-Fidelity Simulation Study: Mixed Qualitative-Quantitative Study.

BACKGROUND: Viscoelastic hemostatic assays, such as rotational thromboelastometry (ROTEM) or thromboelastography, enable prompt diagnosis and accelerate targeted treatment. However, the complex interpretation of the results remains challenging. Visual Clot-a situation awareness-based visualization technology-was developed to assist clinicians in interpreting viscoelastic tests. OBJECTIVE: Following a previous high-fidelity simulation study, we analyzed users' perceptions of the technology, to identify its strengths and limitations from clinicians' perspectives. METHODS: This is a mixed qualitative-quantitative study consisting of interviews and a survey. After solving coagulation scenarios using Visual Clot in high-fidelity simulations, we interviewed anesthesia personnel about the perceived advantages and disadvantages of the new tool. We used a template approach to identify dominant themes in interview responses. From these themes, we defined 5 statements, which were then rated on Likert scales in a questionnaire. RESULTS: We interviewed 77 participants and 23 completed the survey. We identified 9 frequently mentioned topics by analyzing the interview responses. The most common themes were "positive design features," "intuitive and easy to learn," and "lack of a quantitative component." In the survey, 21 respondents agreed that Visual Clot is easy to learn and 16 respondents stated that a combination of Visual Clot and ROTEM would help them manage complex hemostatic situations. CONCLUSIONS: A group of anesthesia care providers found Visual Clot well-designed, intuitive, and easy to learn. Participants highlighted its usefulness in emergencies, especially for clinicians inexperienced in coagulation management. However, the lack of quantitative information is an area for improvement.

Rotational thromboelastometry as a biomarker for mortality - The Maastricht Intensive Care COVID cohort.

BACKGROUND: Patients with severe coronavirus disease 2019 (COVID-19) present with persisting hypercoagulability, hypofibrinolysis and prolonged clot initiation as measured with viscoelastic assays. The objective of this study was to investigate the trajectories of traditional assays of hemostasis, routine and tissue plasminogen activator (tPA) rotational thromboelastometry (ROTEM) in COVID-19 patients and to study their association with mortality. METHODS: Patients enrolled within the Maastricht Intensive Care COVID (MaastrICCht) cohort were included. Traditional assays of hemostasis (prothrombin time; PT, fibrinogen and D-dimer) were measured daily and ROTEM EXTEM, FIBTEM and tPA assays were performed weekly. Trajectories of these biomarkers were analyzed over time for survivors and non-survivors using linear mixed-effects models. Additional Fine and Gray competing risk survival analysis was performed for the first available measurement after intubation. RESULTS: Of the 138 included patients, 57 (41 %) died in the intensive care unit (ICU). Over 450, 400 and 1900 individual measurements were available for analysis of routine, tPA ROTEM and traditional assays of hemostasis, respectively, with a median [IQR] follow-up of 15 [8-24] days. Non-survivors on average had prolonged CT (clotting time) and increased fibrinogen compared to survivors. MCF (maximum clot firmness), LOT (lysis onset time), LT (lysis time) and PT measurements increased more over time in non-survivors compared to survivors. Associations persisted after adjustment for demographics and disease severity. EXTEM and FIBTEM CT at intubation were associated with increased 45-day ICU mortality. CONCLUSIONS: ROTEM measurements demonstrate a further increase of hypercoagulability and (hypo)fibrinolysis parameters in non-survivors throughout ICU admission. Furthermore, prolonged CT at intubation was associated with higher 45-day ICU mortality.

Utility of rotational thromboelastometry in the management of massive haemorrhage at a regional Australian hospital.

BACKGROUND: Rotational thromboelastometry (ROTEM) allows targeted and individualised blood product replacement. OBJECTIVES: The study aimed to determine the impact of ROTEM-guided transfusion on the clinical course of patients with acute massive haemorrhage in a regional Australian hospital. METHODS/MATERIALS: A retrospective review of all patients with acute massive haemorrhage that compared the characteristics, blood product use, and clinical outcomes of patients with massive haemorrhage before and after the introduction of ROTEM-guided transfusion. RESULTS: In per-protocol analysis, the 31/97 (32%) with ROTEM-guided transfusion used less packed red blood cells (median [interquartile range]: 6 [6-8] vs. 8 [6-12] units, p = 0.03) than patients whose transfusion was not ROTEM-guided. They were also less likely to receive fresh frozen plasma (2/31 [6%] vs. 45/66 [68%], p < 0.0001) or platelets (2/31 [6%] vs. 31/66 [47%], p < 0.0001); they were, however, more likely to receive fibrinogen products (26/31 [84%] vs. 38/66 [58%], p = 0.01). Patients receiving ROTEM-guided transfusion had lower in-hospital mortality (6/31 [19%] vs. 20/66 [30%], odds ratio 0.55 [95% confidence interval]: 0.20-1.55, p = 0.26) although this did not achieve statistical significance in this small cohort. CONCLUSION: ROTEM-guided massive transfusion of patients with acute haemorrhage in this regional Australian hospital led to a reduction in packed red blood cell, fresh frozen plasma, and platelet utilisation and may also have reduced mortality.

Contemporary tools for evaluation of hemostasis in neonates. Where are we and where are we headed?

The assessment of hemostatic disorders in neonates is crucial, but remains challenging for clinicians. Although the concept of developmental hemostasis is widely accepted among hemostasis specialists globally, it is probably under-recognized by clinicians and laboratory practitioners. In parallel with age-dependent hemostatic status maturation, comprehension of the differences between normal values is crucial for the accurate diagnosis of potential hemorrhagic and thrombotic disorders of the vulnerable neonatal population. This review outlines the basics of developmental hemostasis and the features of the available coagulation testing methods, with a focus on novel tools for evaluating the neonatal hemostatic profile. Common errors, issues, and pitfalls during the assessment of neonatal hemostasis are discussed, along with their impact on patient management. Current knowledge gaps and research areas are addressed. Further studying to improve our understanding of developmental hemostasis and its reflection on everyday clinical practice is warranted.

Basic Principles of Rotational Thromboelastometry (ROTEM®) and the Role of ROTEM-Guided Fibrinogen Replacement Therapy in the Management of Coagulopathies.

Rotational thromboelastometry (ROTEM) is a viscoelastic method, which provides a graphical and numerical representation of induced hemostasis in whole blood samples. Its ability to quickly assess the state of hemostasis is used in the management of bleeding from a variety of causes. The separate activation of particular parts of hemocoagulation in INTEM, EXTEM, and FIBTEM tests allows for a more comprehensive and faster evaluation of the missing component of hemostasis followed by targeted therapy. One of the most common cause of coagulopathy is trauma-induced coagulopathy. Fibrinogen replacement therapy by ROTEM allows for the use of a standard dosage of fibrinogen, which has been shown to be successful in preventing dilutional coagulopathy following colloid and crystalloid replacement and excessive amount of allogeneic blood transfusions. The best reflection of fibrinogen activity is observed in the FIBTEM assay, where fibrinogen replacement therapy is recommended at an MCF (maximum clot firmness) of FIBTEM < 10 mm and FIBTEM A10 < 7 mm. ROTEM also plays an important role in the diagnostic and management of inherited fibrinogen disorders. These can be manifested by bleeding complications, where changes in the MCF parameter are the most useful tool for assessing the effectiveness of fibrinogen replacement therapy. ROTEM-guided bleeding management algorithms effectively reduce the number of transfusions, healthcare costs, and complications, leading to the improvement of patient safety and overall health.

Sepsis Induced Coagulopathy: Bringing Science to the Bedside.

How to cite this article: Samavedam S, Sepsis Induced Coagulopathy: Bringing Science to the Bedside. Indian J Crit Care Med 2023;27(9): 611-612.

Neutralization, by a polyspecific antivenom, of the coagulopathy induced by the venom of Bothrops asper: Assessment by standard coagulation tests and rotational thromboelastometry in a murine model.

Venom-induced consumption coagulopathy and thrombocytopenia are common and potentially severe manifestations of viperid snakebite envenoming since they contribute to local and systemic hemorrhage. Therefore, the assessment of the efficacy of antivenoms to neutralize coagulopathic and thrombocytopenic toxins should be part of the preclinical evaluation of these drugs. To evaluate the efficacy of the polyvalent (Crotalinae) antivenom produced in Costa Rica, in this study we have used a mouse model of coagulopathy and thrombocytopenia induced by the venom of Bothrops asper, based on the bolus intravenous (i.v.) injection of venom. When venom and antivenom were incubated before injection, or when antivenom was administered i.v. immediately after venom injection, venom-induced hemostatic alterations were largely abrogated. We also studied the recovery rate of clotting parameters in conditions where antivenom was administered when mice were coagulopathic. Some parameters recovered more rapidly in antivenom-treated mice than in control envenomed animals, but others showed a spontaneous recovery without antivenom. This is due to a rapid clearance of plasma venom levels in these experimental conditions. This implies that models based on the bolus i.v. injection of venom have limitations for assessing the effect of antivenom in the recovery of clotting alterations once coagulopathy has developed. It is suggested that alternative models should be developed based on a slower systemic absorption of venom. Overall, our findings provide a protocol for the preclinical evaluation of antivenoms and demonstrate that the polyvalent antivenom is effective in neutralizing the toxins of B. asper venom responsible for coagulopathy and thrombocytopenia.

Baseline rotational thromboelastometry (ROTEM) values in a healthy, diverse obstetric population and parameter changes by pregnancy-induced comorbidities.

Background: Point-of-care testing provides a representation of the patient's coagulability status during effective postpartum hemorrhage management. Baseline values of rotational thromboelastometry (ROTEM) have not yet been reported in a heterogeneous obstetric population. This study aimed to establish a baseline for a diverse population representative of the United States. The secondary aim was to evaluate the association of these hematologic parameters with comorbidities, race, and socioeconomic factors. Methods: The study was a retrospective review of collected ROTEM values of women undergoing vaginal or cesarean delivery with a history of or at risk for postpartum hemorrhage. Patients were divided into healthy and comorbid groups. Exclusion criteria for both groups included active or recent bleeding, receipt of blood products or clot-enhancing factors, and liver disease. Mean values of ROTEM by race and comorbidities were included. Median values were reported for intrinsic pathway thromboelastometry (INTEM), extrinsic pathway thromboelastometry (EXTEM), and fibrin polymerization thromboelastometry (FIBTEM) amplitude at 10 minutes (A10) and 20 minutes (A20), coagulation time, clot formation time, and maximum clot firmness. Results: A total of 681 records were reviewed; 485 met inclusion criteria, and 267 met healthy criteria. The mean (standard deviation) demographics for maternal age (years), body mass index (kg/m2), and gestational age (weeks) were 32.2 (5.7), 34 (7.3), and 35.4 (5), respectively. The median INTEM, EXTEM, and FIBTEM A10 were 63, 65, and 23 mm. The mean for INTEM, EXTEM, and FIBTEM A10 was increased for those who were Black or obese, whereas a decreased FIBTEM and EXTEM A10 was noted in those who were Asian or those who had the hemolysis, elevated liver enzymes, low platelet syndrome. Conclusions: Our heterogeneous population presents ROTEM values within the interquartile range of those previously reported in European studies. Black race, obesity, and preeclampsia were associated with hypercoagulable profiles.

Rotational ThromboElastometry-guided blood component administration versus standard of care in patients with Cirrhosis and coagulopathy undergoing Invasive ProcEdures (RECIPE): study protocol for a randomised controlled trial.

BACKGROUND: Patients with cirrhosis often undergo invasive procedures both for management of complications of their advanced liver disease, including treatment for hepatocellular carcinoma, as well as underlying comorbidities. Despite a current understanding that most patients with cirrhosis are in a rebalanced haemostatic state (despite abnormalities in conventional coagulation tests, namely INR and platelet count), patients with cirrhosis are still often given prophylactic blood components based on these conventional parameters, in an effort to reduce procedure-related bleeding. Viscoelastic tests such as Rotational Thromboelastometry (ROTEM) provide a global measurement of haemostasis and have been shown to predict bleeding risk more accurately than conventional coagulation tests, and better guide blood product transfusion in a number of surgical and trauma-related settings. The aim of this study is to assess the utility of a ROTEM-based algorithm to guide prophylactic blood component delivery in patients with cirrhosis undergoing invasive procedures. We hypothesise that ROTEM-based decision-making will lead to a reduction in pre-procedural blood component usage, particularly fresh frozen plasma (FFP), compared with standard of care, whilst maintaining optimal clinical outcomes. METHODS: This is a multi-centre randomised controlled trial comparing ROTEM-guided prophylactic blood component administration to standard of care in patients with cirrhosis and coagulopathy undergoing invasive procedures. The primary efficacy outcome of the trial is the proportion of procedures requiring prophylactic transfusion, with the primary safety outcome being procedure-related bleeding complications. Secondary outcomes include the amount of blood products (FFP, platelets, cryoprecipitate) transfused, transfusion-related side effects, procedure-related complications other than bleeding, hospital length of stay and survival. DISCUSSION: We anticipate that this project will lead to improved prognostication of patients with cirrhosis, in terms of their peri-procedural bleeding risk. We hope to show that a significant proportion of cirrhotic patients, deemed coagulopathic on the basis of standard coagulation tests such as INR and platelet count, are actually in a haemostatic balance and thus do not require prophylactic blood product, leading to decreased and more efficient blood component use. TRIAL REGISTRATION: RECIPE has been prospectively registered with the Australia and New Zealand Clinical Trials Registry on the 30th April 2019 ( ACTRN12619000644167 ).

Establishing Pediatric Reference Ranges for Rotational Thromboelastometry.

OBJECTIVES: The aim of our investigation was to establish normal pediatric reference intervals (PRIs) for rotational thromboelastometry (ROTEM) Delta assays in a representative group of healthy children, 0 to 18 years of age, at our institution. METHODS: This was a prospective study of healthy pediatric patients undergoing elective minor surgery requiring placement of an intravenous cannula. The sample size for patients was 20 per age group of either sex from 5 different age groups based on coagulation system maturity: 0 to 6 or fewer months, more than 6 to 12 or fewer months, more than 1 year to 5 or fewer years, more than 5 to 11 or fewer years, and more than 11 to 18 or fewer years. ROTEM Delta assays assessed include the EXTEM, INTEM, and FIBTEM. RESULTS: We defined 2 sets of ROTEM PRIs for our patient population: one for patients 11 years or younger and one for children more than 11 years of age. For those 11 years or younger, the PRIs were derived from the 2.5th and 97.5th percentiles from the 0 to 11 age groups. For those older than 11 years, previously published adult reference intervals validated internally with adult normal samples were used. CONCLUSIONS: The 2 sets of PRIs were embedded into our electronic medical record, allowing clinicians to easily interpret their patient's ROTEM results against age-verified reference ranges, enabling them to make informed transfusion decisions.

Rotational Thromboelastometry (ROTEM®) in Relation to Inflammatory Biomarkers and Clinical Outcome in COVID-19 Patients.

Background: The pathogenesis of hypercoagulability in COVID-19 patients is complex and not fully understood. Rotational thromboelastometry (ROTEM®) is a viscoelastic method that allows the definition of a patient's hemostatic profile. This study aimed to assess the relationship between ROTEM® parameters, the profile of inflammatory cytokines, and clinical outcomes in COVID-19 patients. Methods: A total of 63 participants (n = 29 symptomatic non-ICU COVID-19 patients, and n = 34 healthy controls) were prospectively included in the study. We assessed the relationship between the parameters of three ROTEM® tests (NATEM®, EXTEM®, and FIBTEM®) and levels of CRP, interleukin-8, interleukin-1ß, interleukin-6, interleukin-10, tumor necrosis factor, interleukin 12p70, and clinical outcomes. Results: ROTEM® indicated hypercoagulability in COVID-19 patients in all the tests performed. The levels of all inflammatory cytokines were significantly higher in COVID-19 patients. NATEM more frequently detected hypercoagulability in COVID-19 patients compared to EXTEM. The strongest correlations with inflammatory biomarkers and CT severity score were with FIBTEM parameters. The elevated maximum clot elasticity (MCE) in FIBTEM was the strongest predictor of poor outcomes. Conclusions: Increased FIBTEM MCE may be associated with greater severity of COVID-19. Non-activated ROTEM (NATEM test) seems to be more valuable for detecting hypercoagulability in COVID-19 patients compared to the tissue factor activated test (EXTEM).

Clinical Use of Canine Thawed Refrigerated Plasma: A Historical Case Series.

Thawed plasma (TP) refers to defrosted fresh frozen plasma stored refrigerated. TP is used in human medicine for the rapid provision of coagulation factors and resuscitation of haemorrhagic shock, but its use in dogs is poorly described. The objectives of this historical case series were to describe the reasons for TP transfusion, treatment outcomes, and adverse events associated with canine TP transfusions in a veterinary teaching hospital. We hypothesised that TP would be used most commonly for the treatment of haemorrhage secondary to anticoagulant rodenticide intoxication and trauma. Blood bank plasma transfusion logs were searched to identify dogs that received at least one unit of TP between December 2015 and June 2021. Briefly, 166 dogs received a total of 262 units of TP. Anticoagulant rodenticide intoxication (37/166, 22.3%) was the most common reason for transfusion, followed by traumatic haemorrhage (23, 13.9%) and spontaneous haemoperitoneum (22, 13.2%). The majority of dogs received one unit of TP (111/166, 67.1%) and pRBCs were commonly simultaneously transfused with TP (65, 39.2%). Severe prolongations of prothrombin time and activated partial thromboplastin time were reduced following TP transfusions. Allergic reactions were the most common transfusion reaction (19/166, 11.4%). Most dogs survived to discharge (101/166, 60.8%).