Clot Formation Time Research Articles

Evaluation of a Point-of-Care-Viscoelastic Coagulation Device in Hispaniolan Amazon Parrots (Amazona ventralis).

Viscoelastic testing evaluates the formation and lysis of a clot over time, allowing more complete assessment of patient hemostasis in real time, whereas traditional tests, such as prothrombin time and partial thromboplastin time, only measure coagulation factor function. Patient-side viscoelastic coagulation monitors are easy to use, portable, and provide faster turnaround time than commercial laboratories. Viscoelastic testing requires only 0.2 mL of blood and is useful in diagnosing and treating hemostatic disorders. Currently, there is no standardized coagulation testing method across bird species. In this cross-sectional study, a viscoelastic coagulation device, the Entegrion Viscoelastic Coagulation Monitor-Vet (VCM-Vet), was evaluated. Blood samples were obtained from 26 Hispaniolan Amazon parrots (HAPs) (Amazona ventralis) under manual restraint. Results were recorded on the device as graphical output with quantitative viscoelastic measurements. Results were reported using standard rotational thromboelastometry terminology, including clotting time, clot formation time, alpha angle, maximum clot firmness, clot firmness amplitude at 10 and 20 minutes after clot formation, and clot lysis at 30 and 45 minutes. The median clotting time was 463 seconds (reference interval: 56-1635 seconds), the mean clot formation time was 704.7 seconds (reference interval: 172-1697 seconds), the mean alpha angle was 27.3 (reference interval: 7-60), and the mean maximum clot firmness was 15.4 (reference interval: 7-25). Statistical analysis found that all parameters were normally distributed aside from clotting time in seconds. There was no appreciable breakdown of the clot during the 60-minute device runtime, and there was no significant difference in any parameter based on sex. The VCM-Vet produced clotting times for this population of HAPs and enabled the creation of reference intervals. Based on our findings, the VCM-Vet can be used to assess clot potential in HAPs and possibly other avian species.

Comparative analysis of the hemostatic effect of systemic recombinant Factor VIIa and exogenous fibrin monomer in an experimental model of heparinization and posttraumatic blood loss

This article presents the results of a study of the systemic hemostatic action of recombinant Factor VIIa in a rabbit model of heparin-induced coagulopathy and posttraumatic bleeding, compared to the administration of exogenous fibrin monomer. The coagulopathy was induced by a single intravenous injection of unfractionated heparin at a dose of 150 IU/kg 15 minutes before injury. Recombinant Factor VIIa (270 μg/kg) or fibrin monomer (0.25 mg/kg) was used as systemic hemostatic agents. One hour after administrating the agents, a standardized liver injury was inflicted, followed by an assessment of blood loss characteristics. Using rotational thromboelastometry and coagulation tests, animal venous blood was analyzed for coagulation time, alpha angle, clot formation time, maximum clot firmness, clot density at 10 minutes, activated partial thromboplastin time, prothrombin time, thrombin time, and fibrinogen concentration. Pharmacologically induced coagulopathy resulted in shifts to a hypocoagulable profile, associated with severe blood loss (1.9 times, p = 0.028) and high animal mortality (26.1%, p = 0.022) compared to the control group. Preventive administration of fibrin monomer or recombinant Factor VIIa reduced posttraumatic blood loss (by 5.4 times, p 0.001, and by 2.1 times, p = 0.009, respectively), resulting in a decrease in mortality rates. However, the administration of these agents did not correct the hypocoagulable profile as observed in thromboelastometry and coagulation tests. These data demonstrate the hemostatic effect of both agents, with a more pronounced effect after fibrin monomer administration, and suggest potential use of low doses of fibrin monomer in trauma-related hemorrhage. The mechanism of action of fibrin monomer requires further investigation. Therefore, fibrin monomer, a fibrinogen derivative obtained from blood plasma, could be a valuable candidate for managing wound bleeding in addition to recommended systemic hemostatics.

Impact of direct oral anticoagulants on ROTEM® variables; a sample size-calculated experimental study

Direct oral anticoagulants (DOAC) are increasingly common, with bleeding events associated with elevated plasma concentrations. Rotational thromboelastometry (ROTEM), a point-of-care tool for assessing secondary hemostasis, has demonstrated a correlation with increasing concentrations of DOAC. However, previous studies have only partially explored this relationship. The primary aim in the current study was to investigate the impact of increasing rivaroxaban concentrations on clotting time (CT) in the EXTEM assay. The secondary aims were to investigate the impact of increasing rivaroxaban concentrations on clot formation time (CFT) and α-angle (AA) and to investigate the impact of increasing concentrations of dabigatran and apixaban on CT, CFT and AA. Blood from 12 healthy volunteers was spiked to anticipated concentrations of rivaroxaban, dabigatran and apixaban at 0, 50, 100, 200, 500 and 1000 µg/L each. Blood with these varying concentrations was analyzed in four different ROTEM assays and CT, CFT and AA were extracted. CT increased linearly with increasing concentrations of all three DOACs. Rivaroxaban and dabigatran spiked blood showed an increase in CT-EXTEM for the 200–1000µg/L concentrations, compared to baseline, and apixaban for the 500–1000 µg/L concentrations. CFT and AA were affected only in supratherapeutic concentrations for all tested DOACs and primarily in the INTEM assay. Among the tested DOACs, apixaban demonstrated the least impact on CT across all assays. In conclusion, ROTEM-derived CT measurements can serve as surrogate markers for DOAC concentrations.

Comparative Investigation of Thromboelastometry and Thrombin Generation for Patients Receiving Direct Oral Anticoagulants or Vitamin K Antagonists.

Background. Alterations induced by direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs) to thromboelastometry and thrombin generation are not well defined. We performed a simultaneous investigation of thromboelastometry and thrombin generation for patients who were chronically anticoagulated with DOACs or VKAs. Methods. A total of 131 patients on DOACs [apixaban (n = 37), rivaroxaban (n = 34), dabigatran (n = 30), edoxaban (n = 30)] and 33 on VKAs were analyzed. Whole blood was analyzed for thromboelastometry and plasma was analyzed for thrombin generation. Results. While the thromboelastometry clotting time (CT) was responsive to the hypocoagulability induced by DOACs or VKAs, clot formation time and maximal clot formation were not. Cumulatively, the parameters denoting the velocity of thrombin generation (lag time, time-to-peak) were relatively less responsive to the hypocoagulability induced by VKAs than DOACs. Conversely, the parameters denoting the quantity of thrombin generation [peak-thrombin and the endogenous thrombin potential (ETP)] were more responsive to the hypocoagulability induced by VKAs than DOACs. Apixaban showed relatively small differences (peak vs. trough) in the plasma concentration and a relatively small (peak vs. trough) difference of hypocoagulability when assessed by the CT or the ETP. The CT and the ETP were strongly correlated with DOAC concentrations or with the VKA-INR. Conclusions. DOACs and VKAs altered thromboelastometry and thrombin generation to an extent that probably reflects the mode of action of these drugs and may also have practical implications for patients' management. Apixaban showed a small difference of hypocoagulability (peak vs. trough), suggesting a more stable anticoagulation over the daily course of treatment. Based on the correlations of the CT or the ETP vs. the DOAC concentrations, we estimated that critical values of the CT or the ETP would correspond to DOAC concentrations of 400 or 20 ng/mL. Whenever dedicated tests for DOAC concentrations are not available, the CT or the ETP can be used as surrogates to evaluate the level of anticoagulation induced by DOACs.

Establishing a Rabbit Blood Bank: An Assessment of Storage Lesion

Introduction: In trauma settings, hemorrhage and its related complications are one of the major causes of mortality. Blood, blood products, and fluid replacement are the mainstay of treatment in such cases. However with storage, the viability and shelf life of stored products start to decline, reducing their quality when administered. This, in turn, necessitates a validated and flexible model that can be tailored to transfusion needs without affecting product quality. In this study, we established a leporine blood banking model that meets established human requirements to support translational resuscitation studies. Crossmatching was performed to assess risk of hemolytic transfusion reaction. To assess the storage lesion, we analyzed hematology and hemostatic function out to 28 days of cold storage. Methods: Juvenile (4-8 months old) male New Zealand White rabbits from Envigo (strain Hsd:Hra NZW (SPF)) (n=11) were anesthetized with their vitals monitored to ensure adequate plane anesthesia. Whole blood and plasma-designated units were collected via direct cardiac exsanguination. Units were collected (n=11) in 100 milliliter (mL) animal blood bags containing 24% CPDA and stored at 4°C upright. Initially, samples (first n=3) were analyzed on days 0 (collection day), 3, 6, 9, 12, 16, and 21. Sampling was then adjusted to days 0, 4, 7, 10, 14, and 21 for the following n=2, and day 28 was also added for the remaining n=6. Complete blood counts (CBC), rotational thromboelastometry (ROTEM), and collagen agonist impedance aggregometry (IA) were performed to assess changes over storage duration. Before ROTEM analysis, units were recalcified with 1 M CaCl2 1:100 Vol:Vol to account for the increased citrated concentration. Statistical analysis was performed using one-way ANOVA with Dunnett's test for multiple comparisons. Results: Red blood cell count showed no significant change from baseline mean 3.905 M/uL to 4.157 M/uL over 28 days (mean difference: 0.2523 M/uL, p=0.8379). Hematocrit and hemoglobin levels, initially at mean 26.34% and mean 8.755 g/dL respectively, also remained stable (hematocrit: mean difference: 1.01%, p=0.7257; hemoglobin: mean difference: 0.267 g/dL, p=0.9172) with means of 26.34% and 8.488 g/dl on day 28. Platelet count, starting at mean of 228.2 K/μL, finalized at 161.0 M/ μL did not significantly change (mean difference: 67.2 M/μL, p=0.3402). Hemolysis, however, increased significantly from 0.2191% to 1.008% (mean difference: 0.7889, p=0.0333), though all measures remained below 2%. ROTEM INTEM clotting time (CT) and clot formation time (CFT) showed no significant changes from baselines of 188.7 sec to 201.3 sec and 68.0 sec to 179.4 sec respectively (CT: mean difference: 12.57 sec, p=0.3171; CFT: mean difference: 111.4 sec, p=0.2118). INTEM maximum clot firmness (MCF) decreased significantly from 56.86 sec to 25.60 sec (mean difference: 31.26 sec, p=0.001). ROTEM EXTEM CT and CFT exhibited no significant changes from baselines of 76.73 sec and 88.32 sec to 125.5 sec and 586.2 sec respectively (CT: mean difference: 48.77 sec, p=0.2367; CFT: mean difference: 497.9 sec, p=0.3677). EXTEM MCF, like INTEM MCF, decreased significantly from 61.05 sec to 23.10 sec (mean difference: 37.95 sec, p <0.001). IA AUC showed no significant change from baseline 15.73 to 8.99 (mean difference: 6.74, p=0.6488). Conclusion: Our study provides a successful methodology for establishing stable leporine whole blood unit manufacturing and storage. This model can be customized to different transfusion requirements and could be utilized to manufacture components. We plan on expanding our sample size with continuous monitoring for all parameters. Our group will also investigate other available blood collection methods (such as vascular access ports for more frequent unit collections) to refine our model, enhance safe and sustainable production and optimize collection strategies.

Correlation of predelivery Rotational Thromboelastometry readings with the risk of postpartum hemorrhage during delivery: The ROTEM Study

Background Inconsistency in defining postpartum hemorrhage (PPH), and the inability of current tools and approaches to accurately predict PPH have led to the exploration of innovative methods. Rotational thromboelastometry (ROTEM) point-of-care technology provides real-time assessment of the clotting process facilitating time-efficient hemostatic interventions. Our study investigates the utility of ROTEM parameters for predicting individual risk of PPH. Methods This multi-site, prospective observational cohort study recruited 92 women who underwent scheduled cesarean delivery and normal spontaneous vaginal delivery at university-affiliated hospitals from 2018 to 2023. We included women between 18 and 50 years old at ≥34 weeks of gestation. Subjects were approached in the hospital pre-admission testing unit during their routine pre-operative blood draws, typically at least 72 h in advance of their planned cesarean delivery. Participants were also enrolled at the hospital once they arrived for admission a few hours before their procedure. ROTEM parameters EXTEM clotting time (CT), clot formation time (CFT), alpha angle, A10, A20, maximum clot formation (MCF), maximum lysis, were measured preoperative. Results We found significant effects of age, blood loss type, delivery mode, gestational age, and maximum lysis on blood loss. The reduced model predicted that every one-percent increase in maximum lysis was associated with a 44-milliliter increase in blood loss and every one-year increase in age was associated with a 19-milliliter increase in blood loss. On average, cesarean deliveries resulted in 522 more milliliters of blood loss than normal spontaneous vaginal delivery. Conclusion The ROTEM EXTEM maximum lysis parameter has a significant effect on blood loss. Larger prospective clinical trials in conjunction with a prompt definition of the ranges of reference values will strengthen these advances to provide a rapid assessment and guide early interventions to prevent severe obstetric bleeding.

Point-of-care viscoelastic coagulation monitoring device shows promise for informing resuscitation strategies in a canine hemorrhagic shock model.

To use a point-of-care viscoelastic coagulation monitoring device (VCM-Vet; Entegrion) and traditional tests to assess hemostatic changes during hemorrhagic shock in dogs. 8 healthy, purpose-bred Beagles were enrolled in a hemorrhagic shock model conducted from September through December 2021. Dogs were anesthetized, had baseline hemostatic variables measured after blood pressure was stabilized at 70 to 80 mm Hg for 10 minutes (T1), had blood withdrawn from a jugular vein to achieve a mean blood pressure of 40 ± 5 mm Hg for 10 minutes (T2), were resuscitated with 100% shed blood, and then had hemostatic variables evaluated 10 minutes later (T3). At each time point, hemostatic variables were measured with traditional tests (Hct, WBC count, platelet count, mean platelet volume, prothrombin time, activated partial thromboplastin time [aPTT], and concentrations of fibrinogen, antithrombin, and D-dimer) and the VCM-Vet device (clot time, clot formation time, α-angle, maximum clot formation, amplitude at 10 minutes [A10], amplitude at 20 minutes [A20], clot lysis index at 30 minutes [LI30], and clot lysis index at 45 minutes [LI45]). All dogs survived without complication. At T2 and T3 (vs T1), samples had significantly higher coagulability (increased median α-angle, A10, and A20) and fibrinolysis (decreased median LI30 and LI45) and significantly longer aPTT; however, all values remained within reference limits. The use of VCM-Vet helped identify complex hemostatic disturbances in dogs with hemorrhagic shock. The use of VCM-Vet shows promise in aiding veterinarians in optimizing resuscitation strategies based on real-time clotting data.

Viscoelastic Hemostatic Testing as a Diagnostic Tool for Hypercoagulability in Liver Transplantation: A Narrative Review.

Liver transplantation is a complex surgical procedure in which various forms of coagulation dysfunction can occur, including perioperative hypercoagulability. The hemostasis balance in liver graft recipients with end-stage liver disease can shift to thrombosis or haemorrhage, depending on the associated risk factors and clinical conditions. Hypercoagulability can result in serious complications such as thromboembolism, which can affect the vessels of the newly transplanted liver graft. Standard coagulation tests (SCTs), such as prothrombin time and activated partial thromboplastin time (aPTT), have a poor ability to diagnose and monitor an early stage of hypercoagulability. Recent studies demonstrated that viscoelastic hemostatic elastic tests (VETs), such as rotational thromboelastometry (ROTEM) and thromboelastography (TEG), are promising alternative tools for diagnosing hypercoagulability disorders. VETs measure clotting and clot formation time, clot strength (maximum clot firmness), fibrin and platelet contribution to clot firmness, and fibrinolysis, which makes them more sensitive in identifying liver graft recipients at risk for thrombosis as compared with SCTs. However, developing evidence-based guidelines for the prophylaxis and treatment of hypercoagulability based on VET results is still needed.

Synergistic effects of rivaroxaban and hypothermia or acidosis on coagulation initiation measured with ROTEM®: a prospective observational study

BackgroundHypothermia and acidosis individually inhibit haemostasis. We designed this study with the aim to investigate whether rivaroxaban combined with hypothermia or acidosis exhibit synergistic inhibitory effects on haemostasis using ROTEM®.MethodsPatients with a clinical indication to start rivaroxaban treatment were prospectively included. Blood samples were collected before initiation of treatment and the day after. All blood samples were in vitro modified with respect to temperature (incubated and analysed at 28, 33, 37 and 40 degrees Celsius (°C)) and pH (6.8, 7.0, 7.2 and 7.4). The temperature and acidosis effects on the ROTEM EXTEM variables clotting time (CT), clot formation time (CFT) and alpha-angle (AA) were measured along with the individual effect of rivaroxaban on the same variables. The additive effect was calculated. The observed (potential synergistic) effects for the temperature and pH modified rivaroxaban samples on the same ROTEM variables, were registered. Differences between the additive and observed (potential synergistic) effects were analysed using matched non-parametric hypothesis testing.ResultsIn total, 13 patients were included. Hypothermia and rivaroxaban exhibited a synergistic effect on CT at 28 °C (p = 0.0002) and at 33 °C (p = 0.0007). The same applied for acidosis at pH 6.8 (p = 0.003) and pH 7.0 (p = 0.003). There were no signs of synergistic effects of rivaroxaban and temperature or acidosis on CFT. In AA there were signs of synergism at 28 °C (p = 0,001), but not at other tested temperatures or pH levels.ConclusionsThe combination rivaroxaban together with hypothermia or acidosis demonstrated inhibitory synergistic effects on haemostasis.Trial registrationThe study was retrospectively registered 2023-03-01 at ClinTrials.gov with NCT05669313.

Features of the functional state of the endothelium and the hemocoagulation system in the formation of placental insufficiency in patients with gestational diabetes mellitus without insulin requirement

Background. There is a lot of data in the literature showing the state of the hemostatic system and endothelium separately in patients with gestational diabetes mellitus (GDM) and placental insufficiency (PI). However, with the combination of the above complications of pregnancy, there is very little research, therefore, the problem requires detailed study.Objective. To determine the contribution of the functional state of the endothelium and the hemocoagulation system to the formation of placental insufficiency in patients with gestational diabetes mellitus without insulin requirement.Materials and methods. A longitudinal cohort comparative study was conducted. The study included 120 patients in the II-III trimester of pregnancy with GDM without insulin requirement. The main group consisted of 70 women whose pregnancy was complicated by sub- and decompensated forms of PN. The comparison group included 50 pregnant women without pathology of the fetoplacental complex. The hemostasis system was studied using clotting tests and thromboelastometry. The concentrations of VEGF-A, total nitrite (NO2 total), endogenous nitrite (NO2 endogenous), nitric oxide (NO) in peripheral blood were determined by ELISA. Comparison of continuous quantitative data was carried out using the Mann-Whitney test, which was calculated using the MedCalc 15.8 application program. The null hypothesis was rejected at p<0.05.Result. The value of the integral index of coagulation, onset time and initial speed of clot formation in the main group was statistically significantly higher than in patients in the comparison group, p<0.05. The level of VEGF-A in pregnant women of the main group was statistically significantly lower than that in the comparison group, p<0.05. The indicator of total NO2 and NO in the main group was statistically significantly lower than in the comparison group, p<0.05. The endogenous NO2 indicator did not differ statistically significantly between groups.Conclusion. In patients with GDM on diet therapy and PN, endothelial dysfunction and, as a consequence, hypercoagulation occur.

A Deployable Viscoelastic Coagulation Monitor Enables Point-of-Care Assessment of Coagulopathy in Swine With Polytrauma.

Absence of pre-hospital coagulation tests challenges prompt management of hemostasis after trauma. The Viscoelastic Coagulation Monitor (VCM, Entegrion, Durham, NC) is a hand-held coagulation test for point-of-care. We evaluated VCM in a translational swine polytrauma model, hypothesizing that VCM correlates with a laboratory reference method, the TEG 5000 (Haemonetics, Boston, MA), and can identify coagulopathic phenotypes relevant to trauma. Our secondary hypothesis was that pre-warming of VCM disposable test cartridges using a heating plate versus pre-warming of cartridges by carrying the cartridge in the user's pocket does not significantly alter results. This study was conducted in tandem with a parent study involving anesthetized, mechanically ventilated swine (n = 20; 54 ± 5 kg) that encountered traumatic brain injury, pulmonary contusion and hemorrhage, or combination/polytrauma injury. Blood was collected at baseline, post-injury, post-shock, post-transfusion, and 6-, 24-, and 48 h post-injury to perform VCM at point-of-care. Within-group effect of time was assessed. Spearman correlation examined linear relations between VCM and standard laboratory-based coagulation tests; as well as lactate, ionized calcium, and body temperature. Logistic regression examined predictiveness of VCM to identify coagulopathic phenotypes, with receiver operator characteristic curves generated to assess diagnostic capability. At a subset of timepoints, necessity of pre-warming the VCM test cartridge using a heating plate versus pre-warming the cartridge by placement in the user's pocket was assessed by conducting simultaneous tests on two separate instruments, with results analyzed by paired t-test with crossover design. VCM revealed time-dependent changes in clotting time, clot formation time (CFT), alpha, maximum clot firmness (MCF), and lysis index (LI30). All VCM metrics correlated with the respective TEG 5000 metrics, with strongest correlation for VCM MCF with TEG MA (rhos = 0.77, P < .0001) and VCM LI30 with TEG LY30 (rhos = -0.76, P < .0001). VCM demonstrated good (area under the curve >0.70) to excellent (area under the curve >0.90) diagnostic accuracy in detection of low platelet count (MCF), low hematocrit (clotting time, clot formation time, alpha, and MCF), low fibrinogen (MCF), and high fibrinogen (alpha, MCF). There was no statistically or clinically relevant effect of cartridge warming method on results. In a trauma model, VCM detected significant changes in coagulation at point-of-care in a simplified portable form factor. VCM could enable informed hemostasis management in pre-hospital settings where coagulations tests are unavailable, pending further validation in clinical trials.

Prospective cohort study of rotational thromboelastometry in established biliary obstruction: dispelling the myth of auto-anticoagulation

BackgroundPatients with obstructive jaundice are conventionally described as hypocoagulable due to vitamin K malabsorption. However, associated underlying malignancy and synthetic liver dysfunction are mediators of hypercoagulability. The actual effect of biliary obstruction on the coagulation profile is not well characterised. This study aimed to define the coagulation status of patients with established biliary obstruction using rotational thromboelastometry (ROTEM). MethodsThis prospective cohort study, conducted in an Australian metropolitan hospital, included patients with a total bilirubin level of >150 umol/L and biliary obstruction on imaging. The primary outcome was the coagulation profile assessed using ROTEM. Results20 patients were included (median age 74.5 years), 15 were male and 17 had a malignant cause for biliary obstruction. The median bilirubin level was 209 umol/L (IQR: 175.0 umol/L – 255.8 umol/L). On ROTEM, all patients had normal or reduced clot formation times, and normal or increased maximum clot firmness. This confirmed all patients had a normal or hypercoagulable clotting profile, and none were auto-anticoagulated. Vitamin K administration before ROTEM did not vary the coagulation profile. DiscussionPatients with established biliary obstruction and jaundice, predominantly due to malignancy, were normo or hypercoagulable. The belief that obstructive jaundice is associated with a hypocoagulable state should be questioned.

Tocilizumab reduces hypercoagulation in COVID-19 – Perspectives from the coagulation and immunomodulation Covid assessment (Coag-ImmCovA) clinical trial

BackgroundDespite medical interventions, COVID-19 continues to persist at pandemic proportions. A hypercoagulation state was rapidly observed in the severely ill, and the incidence of thromboembolic events remains elevated. Interleukin inhibitors have demonstrated positive effects on the hyperactivation of the immune system in COVID-19, with the interleukin-6 inhibitor tocilizumab showing promising results in reducing mortality. Nevertheless, the impact of interleukin inhibitors on the coagulation system remains incompletely understood. MethodsIn this clinical trial conducted in Stockholm, Sweden, interleukin inhibitors, namely anakinra (ANA) or tocilizumab (TOCI), were randomly administered in addition to standard care (SC) to hospitalized patients with COVID-19. A control group received only SC. The primary outcome sought to measure effects on global hemostasis, as indicated by changes in functional coagulation tests, specifically Rotational Thromboelastometry (ROTEM) or Overall Hemostatic Potential (OHP), visualized through scanning electron microscopy images. Secondary outcomes included effects on conventional coagulation laboratory tests. ResultsThe study enrolled 74 patients who were randomized to receive either ANA or TOCI in addition to SC, or SC alone. In the TOCI group, ROTEM variables exhibited less hypercoagulation after 29 days compared with ANA or SC treatment groups, characterized by prolonged clot formation time and decreased clot firmness. OHP decreased, but there were no significant differences among the three treatment groups. Plasma fibrinogen levels, initially elevated, decreased significantly in TOCI recipients over time. ConclusionTocilizumab treatment demonstrated a significant reduction of hypercoagulation in hospitalized COVID-19 patients, by improvements in both global coagulation tests and conventional laboratory tests, in comparison with anakinra or SC alone. This finding underscores the significance of tocilizumab as a viable treatment option in severe COVID-19 cases, with the potential to decrease thrombosis incidence.

Changes of coagulation function and platelet parameters in preeclampsia and their correlation with pregnancy outcomes.

Preeclampsia (PE) is a severe pregnancy complication characterized by significant alterations in coagulation function. This study aims to analyze the correlation between coagulation function, platelet parameters, and pregnancy outcomes in PE patients. Clinical data, along with blood and urine samples, were collected from 168 PE patients and 128 healthy pregnant women. General demographic and laboratory testing data were recorded, and maternal and fetal outcomes were followed up. Data were analyzed using Kaplan-Meier and logistic regression analyses. In mild PE patients, thrombin time (p=.000), platelet distribution width (PDW) (p=.000), and clot formation time (p=.000) were increased, while prothrombin time (p=.000) and fibrinogen (p=.045) were reduced. With increasing PE severity, prothrombin time (p=.000), platelet count (PLT) (p=.000), mean platelet volume (MPV) (p=.000), plateletcrit (p=.000), maximum amplitude (MA) (p=.000), and coagulation index (p=.001) decreased, whereas activated partial thromboplastin time (APTT) (p=.000), thrombin time (p=.002), D-dimer (p=.026), and PDW (p=.000) increased. Lower prothrombin time (p=.048), PLT (p=.004), and coagulation index (p=.026) or higher APTT (p=.032), thrombin time (p=.044), D-dimer (p=.023), and PDW (p=.016) were associated with a higher risk of poor pregnancy outcomes. Thrombin time was identified as an independent risk factor (p=.025, OR=2.918, 95% CI: 1.145-7.436), whereas gestational age was an independent protective factor (p=.000, OR=0.244, 95% CI: 0.151-0.395). This study demonstrates that specific coagulation and platelet parameters are significantly associated with PE severity and adverse pregnancy outcomes. These findings highlight the importance of monitoring coagulation function in PE patients to improve clinical management and outcomes.

Beyond Trauma-Induced Coagulopathy: Detection of Auto-Heparinization as a Marker of Endotheliopathy Using Rotational Thromboelastometry.

Background/Objectives: The complexity of trauma-induced coagulopathy (TIC) is a result of the unique interactions between the patient, trauma, and resuscitation-related causes. The main objective of trauma resuscitation is to create the optimal milieu for both the development of immediate reparatory mechanisms and the prevention of further secondary injuries. Endotheliopathy represents one of the hallmarks of trauma-induced coagulopathy, and comprises endothelial dysfunction, abnormal coagulation, and inflammation, all of which arise after severe trauma and hemorrhagic shock. Methods: We retrospectively and descriptively evaluated 217 patients admitted to the Bucharest Clinical Emergency Hospital who met the Berlin criteria for the diagnosis of multiple trauma. Patients with high suspicion of auto-heparinization were identified according to the dynamic clinical and para-clinical evolution and subsequently tested using rotational thromboelastometry (ROTEM). The ratio between the clot formation time (CT) was used, obtained on the two channels of interest (INTEM/HEPTEM). Results: Among the 217 patients with a mean age of 43.43 ± 15.45 years and a mean injury severity score (ISS) of 36.98 ± 1.875, 42 patients had a reasonable clinical and para-clinical suspicion of auto-heparinization, which was later confirmed by the INTEM/HEPTEM clotting time ratio in 28 cases (12.9% from the entire study population). A multiple linear regression analysis highlighted that serum lactate (estimated 0.02, p = 0.0098) and noradrenaline requirement (estimated 0.03, p = 0.0053) influenced the CT (INTEM/HEPTEM) ratio. Conclusions: There is a subset of multiple trauma patients in which the CT (INTEM/HEPTEM) ratio was influenced only by serum lactate levels and patients' need for vasopressor use, reinforcing the relationship between shock, hypoperfusion, and clotting derangements. This emphasizes the unique response that each patient has to trauma.

Trauma-induced dysfibrinogenemia: the von Clauss assay does not accurately measure fibrinogen levels after injury

AbstractTrauma patients who sustain severe tissue injury and hemorrhage often receive fibrinogen repletion to avert coagulopathy and achieve hemostasis. However, fibrinogen supplementation has not shown a benefit in trauma patients with coagulopathy. The von Clauss functional fibrinogen assay is the primary indication for fibrinogen transfusion. This assay, however, infers fibrinogen levels optically via in vitro clot formation time and does not directly measure the quantity or quality of plasma fibrinogen. We hypothesized that the Clauss fibrinogen activity assay does not accurately reflect true fibrinogen levels in severely injured patients. Here, we demonstrate normal baseline plasma fibrinogen levels as measured by mass spectrometry despite coagulopathic Clauss values in severely injured patients. This discrepancy is most significant in patients with coagulopathy (international normalized ratio of >1.3) or with high shock, and persists even after fibrinogen repletion. These data highlight the need to reevaluate clinical testing of fibrinogen activity and transfusion criteria for the critically injured, and indicate that correcting shock and the oxidative, inflammatory milieu of trauma may be more effective at improving fibrinogen activity. This trial was registered at www.ClinicalTrials.gov as #NCT01838863.

Platelet transfusion prior to major surgery in a thrombocytopenic dog

AbstractFresh platelet concentrate (FPC) is described as the product of choice for the control of bleeding due to severe thrombocytopenia and has recently become commercially available in the UK. We report a successful, prophylactic FPC transfusion when given in combination with tranexamic acid prior to fracture repair in a 4‐year‐old Whippet. The patient presented with right radial and ulnar fractures and severe thrombocytopenia (platelet count 23 × 109/L). Viscoelastic coagulation monitoring (VCM) revealed coagulopathy, with prolonged clot formation times, but other coagulation parameters were within normal limits. One unit (65 mL) of FPC was given pre‐operatively. The dog underwent surgery without excessive bleeding and experienced no complications. Post‐transfusion VCM showed improved clot formation and clot strength. Transfusion of FPC in combination with tranexamic acid increased this dog's ability to clot, suggesting that it is an effective perioperative therapy for severely thrombocytopenic patients requiring urgent surgery.

P-275 Advanced hemostasis assessment in endometriosis: strengthening confidence in the safety of hormonal treatments

Abstract Study question Are women with endometriosis in a state of systemic imbalance between pro- and anti-coagulants? Summary answer Women with endometriosis do not seem to exhibit a coagulation imbalance, at least at a systemic level. What is known already A state of platelet hyperactivation potentially leading to a hypercoagulation status has been described in women with endometriosis. This phenomenon could induce an altered local environment, promoting platelet-mediated paracrine changes in endometrial tissue and also increasing cardiovascular risk, which could be worsened by the use of estrogen dependent hormonal treatments. However, despite a slight difference in some coagulation parameters has been observed between women affected and controls, their levels remain, generally, within the normal reference range. Study design, size, duration This prospective case-control study including 101 women seeking infertility consultation at the Infertility Unit of Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano between January and July 2023 aimed to assess hemostasis function beyond traditional coagulation parameters. Participants/materials, setting, methods Blood of women with endometriosis (n = 51) or tubal or male factor infertility (controls; n = 50) was obtained before any ART treatment, and a complete panel of coagulation tests were performed, including basic parameters (aPTT, PT, FVIII, FII, PC, AT, FIV-C, DD, vWF, ADMT) as well as more sophisticated ones, such as Thrombin Generation Assay and Thromboelastometry, providing data on endogenous thrombin potential (ETP), clot formation time (CFT) and maximal clot firmness (MCF). Main results and the role of chance There were no significant differences between cases and controls in terms of age (37 [34-39] vs 36 [33-39]; p = 0.53, respectively) and smoking habits (14% vs 28%; p = 0.14, respectively). Women affected had a lower BMI compared to controls (22.7 [20.9-24.9] vs 21.4 [19.6-23.8]; p = 0.03), as it is usually expected. Results from TGA were expressed as ETP ratio (with-/without- thrombomodulin), and high ones were indicative of thrombomodulin resistance, taken as indexes of procoagulant imbalance; however, it was not different between women with and without the disease (0.75 [0.65-0.82] vs 0.75 [0.66-0.82]; p = 0.82, respectively). Other markers of procoagulant imbalance evaluated by thromboelastometry were also similar between cases and controls, including CFT (66 sec [58-78] vs 65 sec [59-79]; p = 0.69, respectively) and MCF (65 mm [62-68] vs 66mm [63-68]; p = 0.95, respectively). Considering the vWF/ADAMTS13 ratio, recently proposed to be altered in endometriosis, no difference was seen between affected and no-affected women (0.95 [0.76-1.14] vs 0.91 [0.68-1.15]; p = 0.41, respectively). Finally, all the basic coagulation parameters were also similar between groups. Limitations, reasons for caution Our sample size does not allow us to perform sub-analyses regarding the type of endometriosis, although we cannot exclude differences according to the various manifestations of the disease. Also, not having a systemic haemostasis imbalance does not exclude the possibility of local coagulation imbalances. Wider implications of the findings An altered systemic haemostasis could be worsened by the use of hormonal treatments. Our result indicating that there is no coagulation imbalance at a systemic level reassures about the absence of further contraindications to hormonal drugs as a treatment for endometriosis. Trial registration number not applicable

Admission Viscoelastic Hemostatic Assay Parameters Predict Poor Long-Term Intracerebral Hemorrhage Outcomes.

Viscoelastic hemostatic assays (VHAs) provide more comprehensive assessments of coagulation compared with conventional coagulation assays. Although 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. Patients with spontaneous ICH enrolled into a single-center cohort study receiving admission Rotational Thromboelastometry (ROTEM) VHA testing between 2013 and 2020 were assessed. Patients with previous 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 6months. Logistic regression analyses assessed associations of ROTEM parameters with clinical outcomes after adjusting for ICH severity and hemoglobin concentration. Of 44 patients analyzed, the mean age was 64years, 57% were female, and the median ICH volume was 23mL. Poor 6-month outcome was seen in 64% of patients. In our multivariable regression models, slower, prolonged coagulation kinetics (adjusted odds ratio for every second increase in clot formation time 1.04, 95% confidence interval 1.00-1.09, p = 0.04) and weaker clot strength (adjusted odds ratio for every millimeter increase of maximum clot firmness 0.84, 95% confidence interval 0.71-0.99, p = 0.03) were separately associated with poor long-term outcomes. 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.

Hemostatic Status of Neonates with Perinatal Hypoxia, Studied via NATEM in Cord Blood Samples.

Perinatal hypoxia may result in coagulation dysfunction. Diminished blood flow or oxygen to the fetus/neonate during the perinatal period can cause bone marrow and liver function impairment, leading to thrombocytopenia, impaired synthesis of clotting and fibrinolytic factors, and increased destruction of platelets in the small blood vessels. The goal of the present study was to evaluate the hemostatic status of newborns with perinatal hypoxia via the non-activated thromboelastometry (NATEM) assay in cord blood samples. 134 hypoxic neonates born in our maternity unit over a 1.5-year period were enrolled in this observational cohort study, and 189 healthy neonates served as the control group. Participation in the study was voluntary and parents signed informed consent prior to recruitment. Demographic and clinical data were recorded on admission, and the NATEM method was performed on cord blood samples. The following NATEM values were evaluated: clotting time (CT), alpha angle (α-angle), clot formation time (CFT), clot amplitude at 5 and 10 min. (A5, A10), maximum clot firmness (MCF), clot lysis index at 60 min. after CT (LI60), and maximum clot elasticity (MCE). Statistical analysis was conducted utilizing the SAS for Windows 9.4 software platform. Neonates with perinatal hypoxia exhibited decreased fibrinolytic potential in comparison to healthy neonates, as indicated by increased LI60, and this difference was statistically significant (LΙ60: 94 (92-96) Vs 93 (91-95), p value = 0.0001). There were no statistically significant differences noted among the remaining NATEM variables. Our findings indicate decreased fibrinolytic potential in hypoxic neonates in comparison to healthy neonates, suggesting that NATEM could serve as an effective tool for promptly identifying hemostasis dysfunction in this group of neonates.