Viscoelastic Tests Research Articles

Point-of-Care Viscoelastic Hemostatic Assays in Cardiac Surgery Patients: Comparison of Thromboelastography 6S, Thromboelastometry Sigma, and Quantra

Viscoelastic tests allow a reduction in blood product transfusion. Three modern devices are currently available (rotational thromboelastometry [ROTEM] sigma, thromboelastography [TEG] 6S, and Quantra). No study has compared the performances of these 3 devices simultaneously. An observational, nonrandomized cohort study. A single-center of cardiac surgery in a university hospital. A total of 30 consecutive measurements from at least 10 adult patients presenting significant bleeding in the intensive care unit after cardiac surgery INTERVENTION: Viscoelastic tests using ROTEM sigma, TEG 6S, and Quantra were performed concomitantly with conventional coagulation measurements MEASUREMENTS AND MAIN RESULTS: The authors included 16 patients with 31 blood samples. After the exclusion of missing values, 27 samples were analyzed. Correlation with platelet count was as follows: ROTEM, r=0.84 [0.66-0.93], p < 0.0001; Quantra, r=0.83 [0.64-0.92], p < 0.0001; TEG 6S, r=0.64 [0.29-0.83], p=0.001. Correlation with fibrinogen (Clauss assay) was as follows: ROTEM, r=0.85 [0.68-0.93], p < 0.0001; Quantra, r=0.88 [0.74-0.95], p < 0.0001; TEG 6S, r=0.79 [0.55-0.91], p < 0.0001. No difference was observed for the detection of residual circulating heparin (anti-Xa activity >0.1), with 87% of correct identification for Quantra and 80% for both ROTEM and TEG 6S (p=0.3). Time to first results after the beginning of the test was shorter for Quantra than ROTEM and TEG 6S (136 [126-152] seconds v 205 [176-221] seconds, p=0.003 and v 450 [372-516] seconds, p < 0.0001 respectively). ROTEM sigma, TEG 6S, and Quantra performed similarly for exploring platelet count or residual circulating heparin. Thromboelastography 6S presented a weaker correlation with fibrinogen Clauss.

Point-of-care diagnosis and monitoring of fibrinolysis resistance in the critically ill: results from a feasibility study

BackgroundFibrinolysisis is essential for vascular blood flow maintenance and is triggered by endothelial and platelet release of tissue plasminogen activator (t-PA). In certain critical conditions, e.g. sepsis, acute respiratory failure (ARF) and trauma, the fibrinolytic response is reduced and may lead to widespread thrombosis and multi-organ failure. The mechanisms underpinning fibrinolysis resistance include reduced t-PA expression and/or release, reduced t-PA and/or plasmin effect due to elevated inhibitor levels, increased consumption and/or clearance. This study in critically ill patients with fibrinolysis resistance aimed to evaluate the ability of t-PA and plasminogen supplementation to restore fibrinolysis with assessment using point-of-care ClotPro viscoelastic testing (VET).MethodsIn prospective, observational studies, whole-blood ClotPro VET evaluation was carried out in 105 critically ill patients. In 32 of 58 patients identified as fibrinolysis-resistant (clot lysis time > 300 s on the TPA-test: tissue factor activated coagulation with t-PA accelerated fibrinolysis), consecutive experimental whole-blood VET was carried out with repeat TPA-tests spiked with additional t-PA and/or plasminogen and the effect on lysis time determined. In an interventional study in a patient with ARF and fibrinolysis resistance, the impact of a 24 h intravenous low-dose alteplase infusion on coagulation and fibrinolysis was prospectively monitored using standard ClotPro VET.ResultsDistinct response groups emerged in the ex vivo experimental VET, with increased fibrinolysis observed following supplementation with (i) t-PA only or (ii) plasminogen and t-PA. A baseline TPA-test lysis time of > 1000 s was associated with the latter group. In the interventional study, a gradual reduction (25%) in serial TPA-test lysis times was observed during the 24 h low-dose alteplase infusion.ConclusionsClotPro viscoelastic testing, the associated TPA-test and the novel experimental assays may be utilised to (i) investigate the potential mechanisms of fibrinolysis resistance, (ii) guide corrective treatment and (iii) monitor in real-time the treatment effect. Such a precision medicine and personalised treatment approach to the management of fibrinolysis resistance has the potential to increase treatment benefit, while minimising adverse events in critically ill patients.Trial registration: VETtiPAT-ARF, a clinical trial evaluating ClotPro-guided t-PA (alteplase) administration in fibrinolysis-resistant patients with ARF, is ongoing (ClinicalTrials.gov NCT05540834; retrospectively registered September 15th 2022).

Manejo intraoperatório do sangramento em cirurgias de grande porte com métodos viscoelásticos

Perioperative monitoring of blood clotting is essential to estimate the risk of bleeding, to diagnose coagulopathy, and to guide hemostatic therapies during surgical procedures. Assessment of hemostasis and the choice of blood products have traditionally been made based on conventional coagulation tests. However, these tests have limitations, as they have high turnaround times and evaluate only the beginning of the whole clot formation process. Viscoelastic tests are an adequate alternative to the use of traditional methods of hemostasis monitoring, as they allow a global assessment of blood clotting, from the beginning of thrombus generation to its dissolution, with fast point-of-care results. Rotational thromboelastometry is a viscoelastic test that has gained importance in the perioperative setting. The test shows a graphical representation of clot formation in real-time and provides a range of parameters about the structure and kinetics of clot formation. The main recommendations of use of this method include diagnosing complex coagulopathy and guiding the hemostatic therapy in the perioperative setting of major surgery, such as cardiac surgery, liver transplant, major trauma, and bleeding in critical patients. The objective of this study is to present an update on viscoelastic methods (focusing on rotational thromboelastometry) and their applicability in different clinical scenarios.

Abstract TP125: Relationships Of Female Sex With Viscoelastic Hemostatic Assay Coagulation Characteristics After Intracerebral Hemorrhage

Introduction: There are described differences in coagulation between females and males. Specifically, female sex is associated with greater platelet activation and stronger clotting characteristics. It is unclear whether there are relevant coagulation differences identifiable between female and male patients suffering from intracerebral hemorrhage (ICH). Hypothesis: Female sex will be associated with stronger clotting characteristics on whole blood viscoelastic hemostatic assay testing. Methods: Spontaneous ICH patients admitted and enrolled into a prospective observational ICH cohort study between 2009-2020 and who received baseline viscoelastic hemostatic assay testing (Rotational Thromboelastometry: ROTEM) were assessed. Patients with prior anticoagulant use, patients receiving hemorrhage control therapies prior to ROTEM, and secondary etiologies of ICH were excluded from the analysis. Female sex was assessed as the primary exposure variable. The following ROTEM clotting parameters were assessed as the outcome: Coagulation Time (CT) and Maximum Clot Firmness (MCF). We assessed relationships of female sex with these separate ROTEM parameters using multivariable linear regression analyses after adjusting for relevant covariates. Results: Of 57 ICH patients included for analyses, mean age was 65 (SD 14.1), 47% were female, and the median ICH volume was 20.6 mL (IQR 10.1-43.3). There were no baseline intergroup sex differences in demographics, age, or ICH characteristics. Female sex was associated with increased EXTEM MCF (ß 0.323, p&lt;0.05), signifying greater clotting strength, after adjusting for age, race, baseline hematoma volume, and ICH location. Female sex was not associated with other ROTEM parameters. Conclusions: We identified that female sex was associated with stronger clotting characteristics on ROTEM viscoelastic testing. Further work is required to clarify the clinical significance of these findings and their potential specific impacts on radiographic, complication, and clinical outcomes after ICH.

Preparation and properties research of a bifunctional hydrophobic associative polymer drag reduction agent for slick water

AbstractIn this study, the bifunctional hydrophobic associative polymer of Acrylamide/2‐Acrylamido‐2‐Methylpropane Sulfonic Acid/Lauryl Methacrylate/N,N‐dodecyl Acrylamide (AALD12) with better salt resistance and shear resistance was synthesized by free‐radical micelle polymerization for use as a drag reduction in shale slip water fracturing. In deionized water, the critical associative concentration (CAC) of AALD12 was 0.23%. AALD12 was determined to be theoretically usable for a shale reservoir within 240°C based on its TG study. Microstructure, viscoelasticity, and shear recovery tests show that the polymer has good drag reduction potential and shear resistance. The reduction rates of the polymer AALD12 and the drag reduction agent RSH‐1 in clear water were 77% and 73% (RSH‐1 is a commonly used emulsion‐type drag reduction agent in the market). At the same salt concentration (K+ and Ca2+, 50,000 ppm) and flow rate (40 L/min), AALD12 can maintain a maximum reduction rate of about 63%. The drag reduction rate of RSH‐1 in K+ and Ca2+ solutions can only be maintained at about 52% and 28%, respectively. In the shear resistance test, AALD12 and RSH‐1 were each subjected to three times of cyclic shear in the test pipe. The drag reduction rate of the polymer AALD12 solution can still reach more than 72%. The drag reduction rate of the RSH‐1 solution is about 56%. The drag reduction agent has good salt resistance and anti‐shear bifunction.

Viscoelastic coagulation testing in Neonatal Intensive Care Units: advantages and pitfalls in clinical practice.

The expression "developmental hemostasis" indicates the age-related physiological changes occurring during the maturational process of the hemostatic system. Despite the quantitative and qualitative alterations, the neonatal hemostatic system is competent and well-balanced. Conventional coagulation tests do not provide reliable information as they only explore the procoagulants during the neonatal period. In contrast, viscoelastic coagulation tests (VCTs), such as viscoelastic coagulation monitoring (VCM), thromboelastography (TEG or ClotPro), and rotational thromboelastometry (ROTEM), are point-of-care assays that provide a quick, dynamic and global view of the hemostatic process, allowing prompt and individualized therapeutic intervention when necessary. Their use in neonatal care is on the increase and they could help monitor patients at risk of hemostatic derangement. In addition, they are crucial for anticoagulation monitoring during extracorporeal membrane oxygenation. Moreover, implementing VCT-based monitoring could optimize blood product use.

Native Whole Blood (TRUE-NATEM) and Recalcified Citrated Blood (NATEM) Reference Value Validation with ROTEM Delta.

Background: Thromboelastography is a viscoelastic test of whole blood hemostasis. Currently, no reference value exists for native whole blood and recalcified citrated blood without activators. The aim of this study was to compare the results of ROTEM® tests using fresh native blood without decalcification "TRUE-NATEM" with those using decalcified citrated blood "NATEM" and provide reference values for each. Methods: Inclusion criteria were healthy adult volunteers (18-65years). Exclusion criteria were any medical condition or medication affecting coagulation. Native whole blood testing was defined as "TRUE-NATEM-test." For recalcified citrated blood testing, the NATEM function was used on ROTEM®. Result: The reference value for TRUE-NATEM was CT: 872-1595s, A10: 14-34mm, A20: 26-48mm, CFT: 314-839s, MCF: 34-55mm, and alpha angle: 17-40°. The reference value for NATEM was CT: 757-1327s, A10: 19-43mm, A20: 33-55mm, CFT: 219-615s, MCF: 37-61mm, alpha angle: 24-51°, and ML: 0-3%. When comparing the reference value of NATEM to TRUE-NATEM, the CT and CFT values are decreased and the MCF and alpha angle are increased. The recalcification process of citrated blood in NATEM shows significant activation of coagulation. Female healthy volunteers had enhanced coagulation when activators were used. Age-related statistical difference was seen when activators were used. Ethnicity did not show any difference on the ROTEM values. Conclusion: We determined the reference value for native whole blood and recalcified whole blood using ROTEM®. A significant discrepancy in native whole blood and recalcified citrated blood coagulation was found. Our study underlines the importance of native whole blood as the gold standard reference value in coagulation.

“TEG” talks: technology worth spreading?

“TEG” talks: technology worth spreading?

The role of point of care thromboelastography (TEG) and thromboelastometry (ROTEM) in management of Primary postpartum haemorrhage: A meta-analysis and systematic review.

The utility of instantaneous evaluation of coagulation during primary postpartum haemorrhage (PPH) is paramount in the context of empirical blood product transfusion-related risk of dilutional and consumptive coagulopathy and circulatory overload. A profound screening of electronic databases till August 15, 2022 was carried out after being enlisted in PROSPERO (CRD42021275514). Randomized control studies, comparative cohort studies, and cross-sectional studies comparing point-of-care viscoelastic test guided blood product transfusion with empirical transfusion in patients with PPH were included. We retrieved five studies, with a total of 1914 parturient with PPH. Patients receiving transfusion based upon point of care viscoelastic tests had lesser risk of having emergency hysterectomy (Odds ratio (OR) = 0.55, 95% CI 0.32-0.95, I2 = 7%), transfusion-associated circulatory overload (TACO) (OR = 0.03, 95% CI 0.00-0.50), reduced transfusion of fresh frozen plasma (OR = 0.07, 95% CI 0.04-0.14, I2 = 89%), platelets (OR = 0.51, 95% CI 0.28-0.91, I2 = 89%), packed red blood cell transfusion (OR = 0.70, 95% CI 0.55-0.88, I2 = 89%), and had better cost-effective treatment [Mean difference (MD) = -357.5, 95% CI - 567.75 to -147.25, I2 = 93%] than patient received empirical transfusion. However, there was no significant difference in the requirement of ICU admissions (OR = 0.77, 95% CI = 0.46-1.29, I2 = 82%). No mortality was detected across the studies. Point of care viscoelastic assessment guided transfusion in PPH confederates with reduced morbidity. Nevertheless, more studies on the triggering values for transfusion, long-term survival, and cost-benefit in patients with PPH are warranted to establish its utility.

Rheological and tribological behavior of polyacrylamide-base solutions for artificial synovial fluid

Purpose This paper presents tribological and rheological analysis results of artificial synovial fluid base solutions. Special attention was paid to polyacrylamide preparations with different molecular weights and concentrations. Methods Tribological tests were conducted using the Al2O3– CoCrMo friction pair in the presence of investigated lubricants. Confocal microscopy was used to analyze and assess of volume, depth, and width of wear traces. Moreover, the viscosity and viscoelasticity tests of analyzed solutions were carried out. The rheological measurements were focused on the oscillatory tests, which allowed us to determine the elasticity modulus (G ') and viscosity (G''). Results Viscoelastic nature of the tested preparations depends on the strain rate. It has been shown that elastic properties dominate at higher frequencies. The molecular weight of the polymer has a particular influence on these properties. The most promising results were obtained for 6% and 8 % high molecular weight polyacrylamide compositions. Conclusions However, all tested polyacrylamide solutions show better rheological and tribological characteristics than commercial preparation based on hyaluronic acid.

Diagnostics of hemostasiological indicators of blood in patients with cervical cancer: standards, innovative models of the future (Ukraine)

This article focused on “Diagnostics of hemostasiological indicators of blood in patients with cervical cancer: standards, innovative models of the future (Ukraine)”. Aims: The aims of this study are to investigate the current standards, the innovative models, prognostic and predictive value of hemostasiological indicators of blood in patients with cervical cancer and identifications of potential gaps and opportunities in the current standards and innovative models for hemostasiological assessment. Methodology: A descriptive cross-sectional study design was evaluated. Secondary data were collected. Descriptive statistics were obtained and utilised. Results: The result showed that in 2020, Ukraine had 20.3 new cervical cancer cases per 100,000 women, regardless of age. Age-standardised cervical cancer incidence was 14.3 per 100,000 women. In 2020, Ukraine's lifetime cervical cancer risk was 1.4%. It illustrates cervical cancer risk. Prothrombin Time is 11–14 seconds, Activated Partial Thromboplastin Time is 25–35 seconds, fibrinogen is 200–400 mg/dL, and platelet counts are 150,000–450,000/L. Thromboelastography is a viscoelastic test that dynamically assesses blood clot formation, strength, and lysis. This test helps doctors assess cervical cancer patients' haemostatic profile and thrombotic risk and establish thromboprophylaxis regimens. In advanced cervical cancer patients, prothrombin time, APTT, fibrinogen, D-dimer, and platelet count predict thrombotic events and poor prognosis. These signs extend VTE risk. Potential gaps or opportunities include a lack of established practices, few complicated hemostasiological tests, little research, lack of knowledge and teaching, and difficulties with monitoring and follow-up, especially in resource-poor areas. Standardising techniques, expanding access to cutting-edge hemostasiological tests, and remote monitoring, and running education and awareness campaigns are future potentials for research and development. Scientific Novelty: cutting-edge hemostasiological tests in cervical cancer. Conclusion: In conclusion, resolving global cervical cancer mortality disparities needs healthcare, cancer prevention, screening, awareness, socioeconomic variables, and creative hemostasiological evaluation models. Better care, thromboprophylaxis, and collaboration can improve cervical cancer outcomes worldwide.

Individualized Management of Coagulopathy in Patients with End-Stage Liver Disease.

Over the last decades, individualized approaches and a better understanding of coagulopathy complexity in end-stage liver disease (ESLD) patients has evolved. The risk of both thrombosis and bleeding during minimally invasive interventions or surgery is associated with a worse outcome in this patient population. Despite deranged quantitative and qualitative coagulation laboratory parameters, prophylactic coagulation management is unnecessary for patients who do not bleed. Transfusion of red blood cells (RBCs) and blood products carries independent risks for morbidity and mortality, including modulation of the immune system with increased risk for nosocomial infections. Optimal coagulation management in these complex patients should be based on the analysis of standard coagulation tests (SCTs) and viscoelastic tests (VETs). VETs represent an individualized approach to patients and can provide information about coagulation dynamics in a concise period of time. This narrative review will deliver the pathophysiology of deranged hemostasis in ESLD, explore the difficulties of evaluating the coagulopathies in liver disease patients, and examine the use of VET assays and management of coagulopathy using coagulation factors. Methods: A selective literature search with PubMed as the central database was performed with the following.

Systematic reviews on platelet transfusions: Is there unnecessary duplication of effort? A scoping review.

Platelet transfusions are used across multiple patient populations to prevent and correct bleeding. This scoping review aimed to map the currently available systematic reviews (SRs) and evidence-based guidelines in the field of platelet transfusion. A systematic literature search was conducted in seven databases for SRs on effectiveness (including dose and timing, transfusion trigger and ratio to other blood products), production modalities and decision support related to platelet transfusion. The following data were charted: methodological features of the SR, population, concept and context features, outcomes reported, study design and number of studies included. Results were synthesized in interactive evidence maps. We identified 110 SRs. The majority focused on clinical effectiveness, including prophylactic or therapeutic transfusions compared to no platelet transfusion (34 SRs), prophylactic compared to therapeutic-only transfusion (8 SRs), dose, timing (11 SRs) and threshold for platelet transfusion (15 SRs) and the ratio of platelet transfusion to other blood products in massive transfusion (14 SRs). Furthermore, we included 34 SRs on decision support, of which 26 evaluated viscoelastic testing. Finally, we identified 22 SRs on platelet production modalities, including derivation (4 SRs), pathogen inactivation (6 SRs), leucodepletion (4 SRs) and ABO/human leucocyte antigen matching (5 SRs). The SRs were mapped according to concept and clinical context. An interactive evidence map of SRs and evidence-based guidelines in the field of platelet transfusion has been developed and identified multiple reviews. This work serves as a tool for researchers looking for evidence gaps, thereby both supporting research and avoiding unnecessary duplication.

ROTEM-GUIDED TRANSFUSION MANAGEMENT FOR ACUTE TYPE A AORTIC DISSECTION: A SINGLE CENTRE EXPERIENCE

ROTEM-GUIDED TRANSFUSION MANAGEMENT FOR ACUTE TYPE A AORTIC DISSECTION: A SINGLE CENTRE EXPERIENCE

THE QUANTRA PCS, PLATELET CONTRIBUTION TO CLOT STIFFNESS, PARAMETER IS CLINICALLY USEFUL TO IDENTIFY PLATELET-DEPENDENT BLEEDING IN HIGH-RISK CARDIAC SURGERY PATIENTS

<h3>Objective</h3> Postoperative use of platelet function testing in order to rule out microvascular bleeding due to platelet dysfunction after cardiac surgery still lacks strong reference data and reliable cut-off values. We investigated the performance of two different point-of-care viscoelastic devices and platelet aggregometry in expressing surgery-dependent platelet dysfunction and anticipating postoperative major bleeding in a cohort of high-risk patients. <h3>Design and Method</h3> This is a prospective cohort study on 50 adult patients who underwent cardiac surgery with cardiopulmonary bypass (CPB) being on antiplatelet drugs discontinued for no more than 7 days (clopidogrel, prasugrel) or 5 days (ticagrelor). Coagulation and platelet function testing, including QUANTRA, ROTEM and Multiplate were assessed preoperatively and postoperatively. Chest drain blood loss was measured in the first 12 postoperative hours. Perioperative bleeding was assessed using the Universal Definition of Perioperative Bleeding (UDPB) in cardiac surgery, modified to not consider anemia-correcting packed red cells transfusions in absence of bleeding > 600 ml/12 h. Major bleeding was identified as UDPB class II or higher. <h3>Results</h3> The QUANTRA Platelet contribution to Clot Stiffness (PCS) was significantly (P=0.001) reduced after CPB. Multiplate ADPtest was significantly (P=0.001) reduced, as well, whereas TRAPtest was not. The platelet component (PC) as extrapolated by ROTEM data (EXTEM MCF – FIBTEM MCF) was unchanged after CPB, while the A10 PC (PC at 10 minutes) significantly (P=0.001) decreased. At regression analysis of the preoperative and postoperative platelet function parameters, there was a significant linear correlation (P=0.001) for the PCS, A10 PC and ADPtest. At the ROC analysis for the predictive ability of the post-CPB platelet function testing, the best discrimination was obtained by the QUANTRA PCS, with an AUC of 0.788, followed by the ROTEM A10 PC (AUC 0.765) and PC (AUC 0.758). The Multiplate tests did not achieve an AUC > 0.70. The cut off values identified for the QUANTRA PCS (10.5 hPa), the ROTEM A10 PC (38 mm) and for the ROTEM PC (47 mm) yielded a combination of a negative predictive value > 80% and a positive predictive value > 67%. <h3>Conclusions</h3> QUANTRA PCS, ROTEM A10 PC, and Multiplate ADPtest reflect the post-CPB platelet dysfunction, whereas ROTEM PC and Multiplate TRAPtest do not. Major bleeding was predicted with a moderate degree of discrimination by the post-CPB viscoelastic tests (PCS, PC, A10 PC) but not by the Multiplate tests.

Viscoelastic versus conventional coagulation tests to reduce blood product transfusion in patients undergoing liver transplantation: A systematic review and meta-analysis.

Recent literature suggests viscoelastic test (VET)-guided transfusion management could be associated with reduced blood product administration in patients undergoing liver transplantation. To assess the effectiveness of coagulation management guided by VETs compared with conventional coagulation tests (CCTs) in reducing blood product transfusion in patients undergoing liver transplantation. Systematic review and meta-analysis of randomised (RCTs) and nonrandomised clinical trials performed according to PRISMA guidelines. The protocol was previously published (PROSPERO: CRD42021230213). The Cochrane Central Library, PubMed/MEDLINE, Embase and the Transfusion Evidence Library were searched up to 30 th January 2022. Setting: operating room. Patients: liver transplantation recipients. Intervention: use of VETs versus CCTs. Main outcome measures: the primary outcome was the mean number of transfused units for each blood product including red blood cells (RBCs), fresh frozen plasma (FFP), platelets (PLTs) and cryoprecipitate. Secondary outcomes included mortality rate, intensive care unit (ICU) and hospital length of stay (LOS). Seventeen studies ( n = 5345 patients), 15 observational and two RCTs, were included in this review. There was a mean difference reduction in RBCs [mean difference: -1.40, 95% confidence interval (95% CI), -1.87 to -0.92; P < 0.001, I2 = 61%) and FFP units (mean difference: -2.98, 95% CI, -4.61 to -1.35; P = < 0.001; I2 = 98%) transfused in the VETs group compared with the CCTs one. A greater amount of cryoprecipitate was administered in the VETs group (mean difference: 2.71, 95% CI, 0.84 to 4.58; P = 0.005; I2 = 91%). There was no significant difference in the mean number of PLT units, mortality, hospital and ICU-LOS. Our meta-analysis demonstrated that VETs implementation was associated with reduced RBC and FFP consumption in liver transplantation patients without effects on mortality and hospital and ICU-LOS. The certainty of evidence ranged from moderate to very low. Further well conducted RCTs are needed to improve the certainty of evidence.

The efficacy of low molecular weight heparin is reduced in COVID-19.

A significant degree of mortality and morbidity in COVID-19 is through thromboembolic complications, only partially mitigated by anticoagulant therapy. Reliable markers of infection severity are not fully established. This study investigated whether visco-elastic biomarkers predict disease severity on presentation to the Emergency Department (ED) and how they measure response to anticoagulationMETHODS:Patients testing positive for COVID-19 at a large University Teaching Hospital ED were recruited at presentation. Multiple blood samples were taken throughout hospital admission to monitor disease progression with end outcome recorded. Visco-elastic markers, fractal dimension (df) and Time to Gel Point (TGP) which measure the properties of the incipient clot were compared in patients with and without anticoagulation by Low Molecular Weight Heparin (LMWH). TGP and df did not predict severity of infection with COVID-19. Although LMWH prolonged TGP, there was no change in df indicating LMWH did not change clot microstructure. Therapeutic efficacy of LMWH appears blunted in COVID-19 infection. This may be due to the inflammatory state creating a resistance to LMWH activity, which may explain why LMWH appears less effective in COVID-19 compared to other disease states. COVID-19 was not predicted by visco-elastic testing at the time of ED presentation.

Identification of Receptors and Signaling Pathways Mediating the Platelet Contribution to Clotting Parameters in Thromboelastography (TEG)

Viscoelastic testing is used for real-time determination of hemostatic status in patients with acute risk of bleeding. Clot formation and contraction in thromboelastography (TEG) are assumed to be driven by thrombin through its two main actions, the conversion of fibrinogen to fibrin and activation of platelets through protease activated receptors (PARs). Platelet stimulation leads to inside-out activation of αIIbβ3 integrin, a process regulated by the small GTPase Rap1, and fibrin binding to activated αIIbβ3 triggers outside-in signaling and platelet contraction. However, studies have shown no impact of PAR inhibitors on viscoelastic clotting parameters, and the impact of defects in Rap1 signaling on TEG have not been determined. Furthermore, the role of novel ligand-receptor interactions such as fibrin-GPVI on TEG parameters have not been studied. Here we investigated the specific receptors and signaling pathways required for platelet function in standard (kaolin-triggered) TEG using genetic or pharmacological inhibition of platelet proteins in murine and human blood samples. We confirmed the requirement of platelets and αIIbβ3 integrin for mouse whole blood clot formation/contraction in TEG. Loss of the integrin adaptor Talin1 in mouse platelets impaired clotting parameters, but to a lesser extent than αIIbβ3 blockade. We observed no changes in clotting parameters using blood from mice lacking Rap1b, or with combined deficiency of CalDAG-GEFI and P2Y12, the two main pathways mediating Rap1 activation. Deficiency of PAR4, which fully mediates the platelet response to thrombin in mice, only partially reduced the speed of clot formation (α-angle) with no impact on maximal clot strength (maximal amplitude, MA). However, TEG parameters similar to samples lacking platelets were observed for blood from PAR4-deficient mice treated with inhibitors of the GPVI receptor or a key downstream signaling protein Syk. These results were reproduced in human blood samples, where inhibition of both PAR1 and PAR4 combined with Syk inhibition robustly reduced α-angle and MA. In summary, our results suggest that global hemostasis assays such as TEG, which are driven by high concentrations of thrombin, are not sensitive to platelet signaling pathways critical for integrin inside-out activation. Furthermore, we provide evidence that platelet-mediated clot contraction in TEG is dependent on both the thrombin-PAR interaction and GPVI, likely interacting with fibrin. Our findings suggest that current interpretation of platelet function in TEG may not reflect platelet function in vivo, and that novel interactions need to be integrated into clinical assays.

Method Comparison Analysis of Quantra Relative to Rotational Thromboelastometry and Conventional Coagulation Testing in Cardiac Surgery

Background: Perioperative utilization of viscoelastic testing to guide the hemostatic management of patients undergoing cardiac surgery is recommended. Historically thromboelastography (TEG) and rotational thromboelastometry (ROTEM) have been used in this setting. The Quantra platform is a new cartridge-based, point-of-care, viscoelastic testing device that utilizes ultrasound to characterize dynamic changes in the viscoelastic properties of blood during clot formation. At present, limited studies addressing the interchangeability of viscoelastic testing parameters exist. Consequently, we conducted a method comparison of Quantra relative to rotational thromboelastometry (ROTEM) and conventional coagulation testing (CCT) in patients undergoing surgery requiring cardiopulmonary bypass (CPB). Aims: This study aimed to assess the correlation and agreement between Quantra, ROTEM, and CCT results using blood samples from cardiac surgery patients. Methods: Blood samples were collected during cardiopulmonary bypass from 127 adult patients undergoing cardiac surgery requiring CPB (after rewarming to 36°C) and before protamine administration. Samples were evaluated in parallel using Quantra, ROTEM, and CCT. Quantra parameters using the QPlus Cartridge included clot time (CT), heparinase clot time (CTH), clot time ratio (CTR), clot stiffness (CS), fibrinogen (FCS), and platelet (PCS) contributions to CS. ROTEM measurements assessed included CT, clot firmness at 20 minutes (A20) and maximum clot firmness (MCF). CCTs included PT, PTT, fibrinogen concentration, and platelet count. Method comparison analyses were performed using Deming Regression to assess the correlation between comparable parameters of Quantra, ROTEM, and CCT. To compare CS and A20/MCF parameters, ROTEM clot amplitudes were transformed from millimeter to Pascals using a conversion formula [((500*mm)/(100-mm))/100]. Individual test results were evaluated for agreement of clinical classifications (low, hemostatic function decreased; normal, hemostatic function within established reference range; high, hemostatic function elevated) relative to reference intervals using a clinical composite index (CCI). Results: Deming regression analysis demonstrated a moderate to very strong correlation between Quantra and ROTEM parameters, with rs values between 0.56 to 0.91 (Table 1). A strong correlation was observed between FCS and fibrinogen concentration and PCS and platelet count (rs=0.77 and rs=0.70, respectively). Despite showing acceptable correlation, Deming regression showed significant constant and proportional biases when comparing comparable parameters. As assessed by the CCI, the overall percent agreement between the Quantra and ROTEM parameters and Quantra and CCT were 64% to 82% (Table 2) and 50% to 72%, respectively. Analysis of agreement between each modality using Cohen's weighted kappa indicated fair to a substantial agreement between Quantra and ROTEM parameters and slight to moderate agreement between Quantra and CCTs parameters. Conclusion: Findings from this method comparison demonstrate that Quantra parameters correlated strongly with corresponding parameters from ROTEM and CCT. However, observed biases following Deming regression analysis indicate that these viscoelastic platforms are not interchangeable; local reference ranges should be established before adopting and clinical use of alternative platforms. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Blood utilization in liver transplantation (BUILT): A multidisciplinary survey of transfusion practices.

The purpose of this study was to survey liver transplant centers in the United States to assess baseline practices in blood utilization and identify opportunities for standardization to optimize blood use in these complex cases. Two surveys, one for transfusion medicine physicians and the other for anesthesiologists, were distributed to high-volume liver transplant centers. The response rate was 52% for both surveys. The majority of respondents (90%) indicated they issue a standardized number of blood products to start surgeries. The most common number of products issued before the start of cases were 10 red blood cells (RBC) and 10 plasma units with no platelets or cryoprecipitate. On average, fewer RBC (7.5) and plasma (7) units were transfused than issued. Decisions to transfuse RhD+ RBCs to RhD- patients and use antigen untested units in alloimmunized patients were mainly handled on a case-by-case basis. Many centers reported utilizing viscoelastic testing (97%) and cell salvage (97%). Most centers reported standardized, laboratory-based intraoperative transfusion goals for RBCs (65%) and fibrinogen replacement (52%) but lacked a standardized approach for plasma (55%) and platelets (58%). More blood products are issued during surgery than are transfused. Responses from anesthesiology providers suggest a broad consensus on practice. Almost all respondents use viscoelastic testing in the management of intraoperative coagulopathy, either alone or in combination with classical coagulation tests. The majority of programs do not transfuse clotting factor concentrates, including fibrinogen concentrate, prothrombin complex concentrates, and recombinant activated FVII, and do not use antifibrinolytics prophylactically.