Bleeding risk assessment in immune thrombocytopenia.

The bleeding risk in immune thrombocytopenia (ITP) is related not only to low platelet count but also to the presence of platelet dysfunction. However, diagnosing a concomitant platelet dysfunction is challenging as most of the available platelet function assays (PFAs) require a platelet count of greater than 100,000/µL. Sonoclot coagulation and platelet function analyzer works on the principle of viscoelastometry, and results remain unaffected by the platelet counts. To assess the platelet function in adult acute ITP patients with the help of sonoclot coagulation and platelet function analyzer and correlate it with the risk of bleeding. Newly diagnosed acute ITP patients with a platelet count less than 20,000/µL were divided into two groups based on WHO bleeding grade: ITP non-bleeder (ITP-NB) group (WHO bleeding grade ≤1) and ITP bleeder (ITP-B) group (WHO bleeding grade ≥2). Platelet function was assessed by sonoclot in both groups. The patients without significant bleeding (ITP-NB) were followed up monthly for six months with the assessment of platelet function during each contact. Eighty patients (30 ITP-B and 50 ITP-NB) were prospectively included in this study. The median age of patients in the two groups was 37 years and 30 years, respectively. The female-to-male ratio was 4:1 and 1:1 in ITP-B and ITP-NB groups. The median platelet count in ITP-B and ITP-NB was 12000/µL (range 1000-19000/µL) and 8000/µL (range 1000-19000/µL), respectively. Mean platelet functions by sonoclot in both groups were lower than the normal cut-off (>1.6). However, the mean platelet function in the ITP-B group (0.2 + 0.17) was significantly lower than the ITP-NB group (1.2 ± 0.52) (p = 0.01). During the follow-up period of 6 months, patients in ITP-NB with a normal platelet function (>1.6) on sonoclot had lesser episodes (one episode) of clinically significant bleeding than patients with a low platelet function (4 episodes). Patients with acute severe thrombocytopenia and bleeding phenotype have a greater abnormality on platelet function by sonoclot than patients with non-bleeding phenotype. This information may help in taking therapeutic decisions in patients with acute ITP.

Association of Heparin-Like Effect, Factor VII/XIII Deficiency and Fibrinolysis with Rebleeding Risk in Cirrhosis with Acute Variceal Bleeding.

BACKGROUND: Hyperfibrinolysis and coagulation dysfunction may occur in cirrhotic patients with acute variceal bleed (AVB) despite successful endotherapy. AIMS: To prospectively study the association of endogenous heparinoids and coagulation dysfunction with variceal rebleeding and outcome in cirrhosis. METHODS: Consecutive patients were assessed with conventional coagulation tests, SONOCLOT™ [(global(gb) and heparinase(h) treated] and factors VII, VIII, XIII, X, tissue plasminogen activator, and plasminogen activator inhibitor ELISA assays in a university hospital. Heparin-like-effect (HLE) was defined as ≥ 20% difference in paired gb/h-SONOCLOT™ traces for activated clotting time (ACT). RESULTS: Of 143 patients screened, 90 (46.4 ± 11.7 years, males 82.2%, ethanol-related 58.8%) were recruited, who bled from esophageal varices (81,90.0%), gastric varices (6,6.6%), or esophageal varices with portal hypertensive gastropathy (3,3.3%). Twenty (21.7%) had early rebleeding, mainly post-variceal ligation ulcer related (70%). Patients who rebled had low Factor XIII [1.6 (1.2-2.1) vs 2.4 ng/ml (2.0-2.8) P = 0.035] and Factor VII (94.1 ± 46.9 vs. 124.0 ± 50.4, P = 0.023). On receiver operating curve analysis, the gbACT > 252 s (sensitivity 86.8%, specificity 76.9%, P < 0.001), hACT > 215 s (sensitivity 71.1%, specificity 70.3%, P < 0.001), and HLE > 50% (sensitivity 69.5%, specificity 70.3%, P = 0.006) predicted rebleeding. Baseline Factor VIII (HR 1.26; 95% CI 1.17-1.34, P < 0.001), low factor VII (HR 0.89; 95% CI 0.76-0.98, P = 0.035), and lysis (HR 1.25, 95% CI 1.17-1.33, P < 0.001) predicted mortality. Endogenous heparinoids at baseline predicted sepsis (HR 1.8; 95% CI 1.4-6.5; P = 0.022), rebleeding events (HR 1.2; 95% CI 1.1-6.3; P = 0.030), and mortality (HR 1.1; 95% CI 1.0-4.6; P = 0.030). CONCLUSIONS: Hyperfibrinolysis, Factor VII/XIII deficiency, and HLE are associated with rebleeding after AVB. Trial Registration NCT04111120 available from https://clinicaltrials.gov/ct2/show/NCT04111120 .

Determination of Coagulation Parameters by Whole Blood Dynamic Viscoelastic Coagulometry in Strigiformes.

No reference values are available in Strigiformes to evaluate blood coagulation using dynamic viscoelastic coagulometry (DVC) with the Sonoclot (Sienco, Boulder, CO, USA) analyzer. The objectives of this study were 1) to assess the feasibility of DVC in Strigiformes, 2) to calculate the index of individuality of each coagulation parameter, and 3) to assess interspecies variability and establish reference intervals, if relevant, based on the index of individuality. Fresh whole blood samples were obtained from healthy Strigiformes, including 13 barred owls (Strix varia), 10 great horned owls (Bubo virginianus), 6 snowy owls (Bubo scandiacus), and 7 eastern screech owls (Megascops asio), and analyzed with DVC with glass bead (gb) and kaolin clay (k) coagulation activators. Activated clotting time (ACT), clot rate (CR), and platelet function were determined immediately after collection using fresh native whole blood. Intraindividual variability was assessed with a second fresh native whole blood sample from 5 barred owls. Interindividual variability was assessed using a Kruskall-Wallis test. For the parameters gbACT (n = 35), gbCR (n = 34), and kACT (n = 27), no significant differences were detected between species (all P ≥ 0.05). Based on low index of individuality, global Strigiformes reference intervals were determined for gbACT (32.3-852.5 seconds; n = 35), gbCR (0-20.1 units/min; n = 29), and kACT (0-1570.3 seconds; n = 27). In conclusion, DVC can be used in Strigiformes and the gb coagulation activator would be more appropriate when basal individual values are not available in a tested individual.

Comparison of the predictive value of thromboelastography and Sonoclot analysis for postoperative bleeding in children undergoing corrective surgery for cyanotic congenital heart disease.

Background: The aim of the study was to compare the predictive value of Sonoclot analysis and thromboelastography (TEG) for postoperative bleeding in children younger than 12 years coming for cardiac surgery for congenital cyanotic heart disease. Methods: This is a prospective, observational study carried out in a single tertiary care military hospital. Ninety patients of the paediatric age group undergoing bypass cardiac surgery for correction of congenital cyanotic heart defect were included in the study. Laboratory-derived values to assess coagulation status (prothrombin time, international normalisation ratio, activated partial thromboplastin time) and point-of-care Sonoclot- and TEG-derived parameters were noted at the start of surgery and postoperatively in all patients. Bleeders were predefined on the basis of chest tube drainage. Results: The incidence of bleeders was 42.2% (38/90 patients), whereas 57.8% (52/90 patients) were non-bleeders. The postoperative R value and preoperative gbPF test were predictive for postoperative bleeders on multivariate analysis. Postoperative gbPF had the highest area under the curve (0.72), with a cut-off value of 1.75, and gbPF had 82% sensitivity and 71% specificity in predicting significant postoperative bleeding in paediatric cyanotic congenital heart surgeries. Transfusion requirements and mechanical ventilation duration were higher in bleeders; however; length of intensive care unit stay, incidence of sepsis and mortality were similar in both the groups. Conclusion: Bleeding in patients undergoing corrective surgery for cyanotic congenital heart disease could be predicted by the preoperative gbPF and postoperative R value. Among these, preoperative gbPF has the maximum predictive value.

Utility of Sonoclot in Prediction of Postoperative Bleeding in Pediatric Patients Undergoing Cardiac Surgery for Congenital Cyanotic Heart Disease: A Prospective Observational Study.

OBJECTIVES: To assess the utility of Sonoclot in prediction of postoperative bleeding in pediatric patients undergoing cardiac surgery with cardiopulmonary bypass for congenital cyanotic heart disease. DESIGN: Prospective, observational study. SETTING: Single university hospital. PARTICIPANTS: Eighty-seven pediatric patients undergoing cardiac surgery for congenital cyanotic heart disease. INTERVENTIONS: Laboratory coagulation parameters (prothrombin time, international normalization ratio, activated partial thromboplastin time, fibrinogen, D-dimer) as well as point-of-care Sonoclot glass bead activation time, clot rate, and platelet function (gbPF) were done before induction of anesthesia and following heparin reversal after termination of cardiopulmonary bypass (CPB) in all patients. MEASUREMENTS AND MAIN RESULTS: Postoperative blood loss was monitored by the amount of chest tube drainage. The primary outcome was to define Sonoclot parameters for prediction of postoperative bleeding. Secondary outcomes studied were amount of postoperative blood loss, transfusion requirement of various blood products, incidence of surgical re-exploration, duration of postoperative mechanical ventilation, intensive care unit and hospital stay. Among studied subjects, 37.9% (33 of 87 patients) were designated as bleeders while 62.1% (54 of 87 patients) were non-bleeders. Lower age, D-dimer, and gbPF test after termination of CPB following heparin neutralization were predictive for postoperative bleeders. Among these, post-protamine gbPF had the highest area under the curve (0.725), 95% confidence interval (0.619-0.831) for prediction of postoperative bleeders. Duration of mechanical ventilation (26.41±36.44 v 8.25±6.36 h, respectively, p = 0.001), intensive care unit stay (7.36 ± 4.05 v 4.96 ± 2.49, p = 0.001), and hospital stay (11.69±4.82 v 8.63±3.48 p = 0.001) were higher in bleeders; however, incidence of re-exploration was comparable between both groups. CONCLUSION: Postoperative bleeders may be predicted independently by post-CPB gbPF, postoperative D-dimer, and lower age of patients. Among these, post-CPB gbPF has maximum predictive value.

Platelet Function Testing Using Sonoclot and TEG6s as a Platelet Transfusion Prediction Tool in Open Heart Surgery.

Introduction The point-of-care test (POCT) is useful for blood coagulation management during cardiovascular surgery. Although thromboelastography (TEG6s) has been reported to have targeted benefits for blood transfusion in cardiac surgery, Sonoclot analysis has not yet been fully validated. In this study, we evaluated the accuracy of Sonoclot, especially platelet function (PF) as a platelet concentrate (PC) transfusion parameter, compared to TEG6s in cardiovascular surgery. Methods This single-center, prospective, randomised trial was conducted at a university hospital. Forty-two adult patients who underwent elective cardiac surgery requiring cardiopulmonary bypass were included in this study between 2017 and 2021. The participants were randomly assigned to the Sonoclot (S) or Sonoclot and TEG6s (ST) groups. The amount of intraoperative PC was determined according to the POCT parameter values at the time of protamine administration. In addition, we investigated the correlation between PF parameters of POCT and platelet count at the end of surgery. Results There was no statistically significant difference in the intraoperative PC volume between the two groups. The Sonoclot PF parameter, PF, was moderately correlated with platelet count at the end of surgery (r=0.5449, p=0.009), and the TEG6s PF parameter showed a strong correlation with platelet count at the end of surgery (r=0.7744, p<0.001). Conclusion There was no statistically significant difference in platelet transfusion volume between the Sonoclot and TEG6s in this study. The correlation between the PF of the Sonoclot and platelet count was moderate. This study suggests that PF of Sonoclot may be a potentiating indicator of PF.

Viscoelastic Testing Methods.

Viscoelastic testing methods examine the real-time formation of a clot in a whole blood sample, and include thromboelastography (TEG), rotational thromboelastometry (ROTEM), and several other testing platforms. They allow for concurrent assessment of multiple aspects of clotting, including plasmatic coagulation factors, platelets, fibrinogen, and the fibrinolytic pathway. This testing is rapid and may be performed at the point-of-care, allowing for prompt identification of coagulopathies to guide focused and rational administration of blood products as well as the identification of anticoagulant effect. With recent industry progression towards user-friendly, cartridge-based, portable instruments, viscoelastic testing has emerged in the 21st century as a powerful tool to guide blood transfusions in the bleeding patient, and to identify and treat both bleeding and thrombotic conditions in many operative settings, including trauma surgery, liver transplant surgery, cardiac surgery, and obstetrics. In these settings, the use of transfusion algorithms guided by viscoelastic testing data has resulted in widespread improvements in patient blood management as well as modest improvements in select patient outcomes. To address the increasingly wide adoption of viscoelastic methods and the growing number of medical and laboratory personnel tasked with implementing, performing, and interpreting these methods, this chapter provides an overview of the history, physiology, and technology behind viscoelastic testing, as well as a practical review of its clinical utility and current evidence supporting its use. Also included is a review of testing limitations and the contextual role played by viscoelastic methods among all coagulation laboratory testing.

Monitoring of Antiplatelet Therapy.

In the late 1990s, the antithrombotic antiplatelet agent, clopidogrel, a P2Y12 inhibitor, was introduced. Around the same time, there was an increase in a number of new methods to measure platelet function (e.g., PFA-100 in 1995), and this has continued. It became evident that not all patients responded to clopidogrel in the same way and that some patients had a relative "resistance" to therapy, termed "high on-treatment platelet reactivity." This then led to some publications to advocate platelet function testing being used for patients on antiplatelet therapy. Platelet function testing was also suggested for use in patients awaiting cardiac surgery after stopping their antiplatelet therapy as a way of balancing thrombotic risk pre-surgery and bleeding risk perioperatively. This chapter will discuss some of the commonly used platelet function tests used in these settings, particularly those that are sometimes referred to as point-of-care tests or that require minimal laboratory sample manipulation. The latest guidance and recommendations for platelet function testing will be discussed following several clinical trials looking at the usefulness of platelet function testing in these clinical settings.

Quantification and optimization of clot retraction in washed human platelets by Sonoclot coagulation analysis.

INTRODUCTION: Clot retraction is a pivotal process for haemostasis, where platelets develop a contractile force in fibrin meshwork and lead to the increased rigidity of clot. The pathophysiological alteration in contractile forces generated by the platelet-fibrin meshwork can lead to haemostatic disorders. Regardless of its utter significance, clot retraction remains a limited understood process owing to lack of quantification methodology. Sonoclot analysis is a point-of-care technique used in clinical laboratories for whole blood analysis that provides in vitro qualitative as well as quantitative assessment of coagulation process from initial fibrin formation to clot retraction. METHODS: Human washed platelets were isolated by differential centrifugation method and analysed via optical imaging, microscopy and Sonoclot analysis using 1-2 × 108 /mL of washed platelets, 1 U/mL of thrombin, 1 mg/mL of fibrinogen and 1 mM of calcium chloride. RESULTS: In this study, we demonstrate the novelty of this instrument in the quantitative evaluation of clot retraction in washed platelets and attempted to optimize the reference range of Sonoclot parameters including ACT - 87.3 ± 20.997, CR - 16.23 ± 3.538 and PF - 3.57 ± 0.629, (n = 10). DISCUSSION: Sonoclot analysis provides a simple and quantitative method to better understand in vitro clot retraction and its modulation by retraction components including platelet count, fibrinogen and platelet-fibrin interaction compared with existing conventional methods. Sonoclot may prove to be a valuable tool in thrombus biology research to understand fundamental basis of blood clot retraction.

Viscoelastic Coagulation Testing in Exotic Animals.

Whole blood viscoelastic coagulation testing (VCT) allows global assessment of hemostasis and fibrinolysis. Although not widely used in exotic animal practice, VCT has been used in exotic animal research settings. Differences in patient demographics and analytical variables can result in dramatically different results with the same analyzer. To improve the utility of VCT in exotic animal medicine, standardization of protocols is necessary to facilitate the establishment of reference intervals. Despite these challenges, the quantitative/qualitative nature of VCT has already proved its real-world value to some clinicians.

Sonoclot® predicts operation time and blood loss after cardiopulmonary bypass in children.

Background: As the circulating blood volume is relatively small in pediatric patients, blood components are quickly lost when bleeding, which make it more difficult to stop the bleeding. Particularly in pediatric cardiac surgery, loss of clotting factors associated with cardiopulmonary bypass (CPB) would likely to be prominent. As a result, bleeding is further promoted and the operation time is extended. In order to search for the relation between clotting factors and the amount of bleeding, we used a viscoelastic point of care test. Objectives: We used Sonoclot® as viscoelastic point of care test to evaluate coagulation function before CPB and before weaning from CPB in pediatric cardiac surgery. Design: Retrospective. Setting: Single-institutional. Participants: We included 55 pediatric patients (median age 13 months [IQR 5-32]) who underwent cardiac surgery under CPB from December 2015 to November 2016. Interventions: None. Measurements and main results: Sonoclot® analysis was performed after induction of anesthesia (pre-data, or baseline data) and before any heparinized saline was given, and right after modified ultrafiltration after weaning from CPB (post-data). Post-data was compared with post-CPB operation time and post-CPB blood loss by multiple regression analysis. Furthermore, effects of fresh frozen plasma (FFP) added on CPB on coagulation function and post-platelet function (describe as PFSC) was assessed. Activated coagulation time (describe as ACTSC) and clot rate (describe as CRSC) showed no significant change between baseline data and post-data. Post-PFSC was worsened by prolonged CPB time (p < 0.05) and correlated to bleeding amount and operation time after CPB (p < 0.05). Total amount of platelet concentrate (PC) transfused was higher in patients with smaller PFSC (p < 0.05). Total amount of FFP and PC transfused correlated with bleeding amount and operation time after CPB (p < 0.05). In the subgroup analysis, PFSC declined in the FFP-included group, whereas there was no significant difference in coagulation function. Addition of FFP to CPB did not significantly affect CR, whereas PFSC deteriorated as CPB time was prolonged (CPB time = 1/(0.0021∗PFSC + 0.0055)). Conclusion: Sonoclot® is useful to evaluate coagulation function in pediatric patients who undergo CPB. Preventive administration of FFP or PC in CPB circuit could reduce bleeding after CPB.

Clinical application of viscoelastic point-of-care tests of coagulation-shifting paradigms.

Bleeding during cardiac surgery, liver transplant, trauma and post partum hemorrhage are often multifactorial and these factors are dynamic as new factors crop up during the course of management. Conventional tests of coagulation offer information of a part of the coagulation system and also is time consuming. Viscoelastic point of care tests (VE POCTs) like rotational thromboelastometry, thromboelastogram and Sonoclot, are based on analysis of the viscoelastic properties of clotting blood and provide information for the entire coagulation pathway. In this comprehensive review being presented here, we have examined the pros and cons of VE POCTs including clinical, cost and survival benefits. The recommendations of the various guidelines regarding use of VE POCTs in various scenarios have been discussed. The review also tried to offer suggestions as to their optimal role in management of bleeding during cardiac surgeries, extracorporeal membrane oxygenation, left ventricular assist devices, liver transplant and briefly in trauma and postpartum hemorrhage.

Principles, Interpretation, and Evidence-Based Role of Viscoelastic Point-of-Care Coagulation Assays in Cirrhosis and Liver Failure.

Background and Aims: Standard coagulation tests such as prothrombin time, activated partial thromboplastin time, and international normalized ratio are determined by liver-synthesized coagulation factors. Despite an increased international normalized ratio, patients with cirrhosis are in a "rebalanced" state of hemostasis as the concomitant effect of reduced protein C, protein S, and thrombomodulin is not evaluated in standard coagulation tests. The cell-based model of hemostasis indicates additional mechanisms such as systemic inflammation, sepsis, and organ failures tip the delicate coagulation balance to an anticoagulant type in acute-on-chronic liver failure. In acute liver failure, thrombin generation and platelet function remain intact despite a marked prolongation in prothrombin time. We aimed to explain the principles, application, and utility of viscoelastic tests such as thromboelastography, rotational thromboelastometry, and Sonoclot. Methods: We reviewed the available literature from MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trial with the search terms 'coagulation', 'cirrhosis', 'acute-on-chronic liver failure', 'thromboelastography', 'thromboelastometry' and 'sonoclot' for cross sectional studies, cohort studies and randomized trials. Results: The point-of-care viscoelastic tests provide actionable targets for correcting the coagulation defect in a patient with bleeding and provide evidence-based algorithms for use in liver disease. A limitation of these tests is the inability to assess vessel injury and endothelial elements. Conclusion: Global coagulation tests provide a comprehensive estimate of coagulation in vitro; however, their use has only been validated in the setting of liver transplantation. Newer guidelines for hemostatic resuscitation are now accepting these POC tests, but additional data are required to validate their use as standard of care.

Clinical Validation of Global Coagulation Tests to Guide Blood Component Transfusions in Cirrhosis and ACLF.

BACKGROUND AND AIMS: Patients with cirrhosis and acute-on-chronic liver failure (ACLF) may have bleeding complications and need for invasive procedures. Point-of-care (POC) coagulation tests like thromboelastography (TEG) and Sonoclot may be better for guiding patient management than the standard coagulation tests (SCTs), like prothrombin time, platelet count and international normalized ratio. METHODS: We prospectively compared and validated the POC tests and SCTs in 70 persons with ACLF and 72 persons with decompensated cirrhosis who had clinical bleeding and checked for episodes of re-bleeding and transfusion requirements. We assessed pre-procedure requirement of blood components when correction was done based on an SCT or POC strategy. RESULTS: Episodes of bleeding were seen in 45% and 28% of ACLF and cirrhosis patient, respectively (p=0.036), with the major site of bleeding being gastrointestinal (31% and 16%, respectively). Platelet counts correlated with TEG-maximum amplitude in cirrhosis (p=0.045) and prothrombin time correlated positively with TEG-reaction (R) time (p=0.032), TEG-Clot kinetics (K) time (p=0.042), Son-activated clotting time (p=0.038) and negatively with clot rate (p=0.043) in ACLF, making these correctable target variables in POC transfusion algorithms. Of 223 procedures, transfusion of fresh frozen plasma and platelet concentrate was reduced by 25% (p=0.035) and 20.8% (p=0.045) by using a POC strategy in 76 patients. Correction of deranged Son-activated clotting time and TEG-reaction time was noted in 68% and 72% after 24 h of fresh frozen plasma transfusion in ACLF and 85% and 80% in cirrhosis, respectively. CONCLUSIONS: Our study clinically validates that POC tests can better detect coagulation defects and transfusion thresholds in ACLF and cirrhosis, whereas use of conventional tests appear to be less suitable in patients with clinical bleeding. TRIAL REGISTRATION: NCT04332484.

Intravenous Tranexamic Acid Improves the Intraoperative Visualization of Endoscopic Sinus Surgery for High-Grade Chronic Rhinosinusitis: A Randomized, Controlled, Double-Blinded Prospective Trial.

Objective: Intraoperative bleeding during endoscopic sinus surgery (ESS) for high-grade rhinosinusitis can be serious and can further obscure the surgical field. This study was designed to evaluate the effect of tranexamic acid (TXA) on the surgical visualization of ESS for high-grade rhinosinusitis. Methods: In total, 60 patients with high-grade chronic rhinosinusitis (Lund-Mackay score 12 or greater) treated by ESS were randomized into two groups: the control group (Group C) or the TXA group (Group T). Each group included 30 patients. Patients in Group T received intravenous TXA, and those in Group C received normal saline. The Boezaart grading scale (BS) score was assessed as the primary outcome. Total blood loss (TBL), whole blood coagulation, and fibrinolysis were assessed by Sonoclot analysis, and complications were recorded and compared between the groups. Result: A significant difference was found in the BS score between Group T and Group C [2.02 (1.88-2.05) vs. 2.27 (2.13-2.41), P = 0.011]. Increases in platelet function (PF) and fibrin degradation time (FDT) were assessed during the operation and showed significant differences between Group T and Group C (P = 0.040 for PF; P = 0.010 for FDT). No difference in complications was found between the two groups. Conclusion: A 15 mg/kg bolus of intravenous TXA before surgery can improve the surgical visualization of ESS for high-grade chronic rhinosinusitis without causing significant adverse effects. Intravenous TXA may be beneficial in ESS for high-grade chronic rhinosinusitis. Clinical Trial Registration: https://www.chictr.org.cn/edit.aspx?pid=121653&htm=4.

Viscoelastic test-based bleeding risk score reliably predicts coagulopathic bleeding in decompensated cirrhosis and ACLF patients.

BACKGROUND AND AIMS: Coagulopathic bleeding risk prediction is challenging in decompensated cirrhosis (DC) by conventional assays. Viscoelastic tests (VETs) are likely to be more useful for assessing coagulation status in these patients. We investigated whether the VET (Sonoclot) parameters with fibrinogen could predict coagulopathic bleeding in these patients. PATIENTS AND METHODS: Coagulation parameters studied in 874 patients [124 compensated cirrhosis (CC), 521 DC, and 229 acute-on-chronic liver failure (ACLF)] and 190 controls. DC patients were enrolled in derivation (n = 266) and validation (n = 255) cohorts. Sonoclot variables [activated clotting time (ACT), clot rate (CR), platelet function (PF), time to peak (TP) and peak amplitude (PA)] and fibrinogen levels were measured. Coagulopathic bleeding was recorded along with 1-year survival. RESULTS: DC patients had prolonged ACT (p < 0.001), depressed CR (p = 0.059), reduced PF (p = 0.09), longer TP (p < 0.001) and smaller PA (p < 0.001), compared to CC and controls (p < 0.001 each). In derivation cohort, 32.3% patients had coagulopathic bleeding. Cox regression analysis of derivation cohort revealed; ACT > 190 s, PF < 1.25 and fibrinogen < 1.2 g/l could predict coagulopathic bleeding and were used to develop a bleeding risk score. In validation cohort; this score was comparable, correlated to real events, and had similar bleed free events with time. The score was also useful in predicting bleed in ACLF patients. In DC patients, 1-year mortality was higher those who bled and received transfusions. CONCLUSION: Viscoelasticity-based bleeding risk score using ACT, PF and fibrinogen, predicts coagulopathic bleeding in DC patients and should be useful in rationalizing transfusion of blood products. We designed a viscoelastic test-based bleeding risk score which is useful in advanced liver disease to predict the coagulation-related bleeding. This figure shows the lower bleeding-free events in advanced cirrhosis with each incremental bleeding risk score.

The neutralization efficacy of expired polyvalent antivenoms: An alternative option.

The expense of production and distribution of snakebite antivenom, as well as its relatively infrequent use, has caused antivenom to be increasingly difficult to obtain and ultimately producing an alarming global shortage. Unused, expired antivenom may represent a significant, untapped resource to ameliorate this crisis. This study examines the efficacy of expired antivenom over time using in vitro, whole blood clotting, and platelet function statistics. Representatives from three years for four different global brands of polyvalent antivenom were chosen and tested against their corresponding venoms as well as other venoms that could display cross-reactivity. These antivenoms include Wyeth Polyvalent (U.S.; exp. 1997, 2001, 2003), Antivipmyn® (Mexico; exp. 2005, 2013, 2017), Biotecfars Polyvalent (Venezuela; exp. 2010, 2014, 2016), and SAIMR (South Africa; exp. 1997, 2005, 2017). Venoms of species tested were Crotalus atrox against Wyeth; C. atrox and Crotalus vegrandis against Antivipmyn®; C. atrox, C. vegrandis and Bothrops colombiensis against Biotecfar; and Bitis gabonica and Echis carinatus against South African Institute for Medical Research (SAIMR). Parameters recorded were activated clotting time (ACT), clotting rate (CR), and platelet function (PF). Preliminary results are encouraging as the antivenoms maintained significant efficacy even 20 y after their expiration date. We anticipate these results will motivate further studies and provide hope in the cases of snakebite emergencies when preferable treatments are unavailable.

Comparison on Anticoagulation and Antiplatelet Aggregation Effects of Puerarin with Heparin Sodium and Tirofiban Hydrochloride: An In Vitro Study.

OBJECTIVE: To detect the anticoagulation and antiplatelet effects of different concentrations of puerarin, heparin sodium and tirofiban hydrochloride on the blood samples of healthy volunteers by Sonoclot coagulation and platelet function analyzer. METHODS: Peripheral blood samples were extracted from 20 healthy volunteers, followed by adding different concentrations of puerarin, heparin sodium and tirofiban hydrochloride. Samples were detected for activated clotting time (ACT), clot rate (CR) and platelet function (PF) by Sonoclot coagulation and platelet function analyzer instrument. RESULTS: For puerarin and heparin sodium, the values of ACT gradually increased, and the values of CR and PF gradually decreased with increasing in drug concentration. There was a linear (or log linear) relationship between ACT, CR, PF value and drug concentration (P<0.01). Corresponding to each value, a regression equation was obtained. For tirofiban hydrochloride, the values of ACT and CR had no significant changes, while PF values gradually decreased with concentration increasing. There was also a linear relationship between PF values and concentrations of tirofiban hydrochloride (P<0.01). Under the same ACT values, the puerarin corresponding CR values (CR = e-0.0062ACT+4.31, P<2.2e-16) were always higher than the corresponding values (CR = e-0.0028ACT+2.79, P-value<2.2e-16) of heparin sodium. For high concentrations of puerarin (e.g. 3.8 mg/600 µL) and tirofiban hydrochloride (e.g. 0.8 µg/600 µL), PF values had no significant difference. However, PF values for high puerarin concentration had a larger variance. CONCLUSIONS: Puerarin has similar anticoagulant and antiplatelet effects with the heparin sodium, and may have a lower hemorrhage risk than heparin sodium when obtained the same anticoagulation effect in the concentration range of this experiment. In addition, for high concentration, puerarin had the same antiplatelet function as tirofiban hydrochloride but with a larger individual variability.

Comparison of citrated and fresh whole blood for viscoelastic coagulation testing during elective neurosurgery.

BACKGROUND: Previous viscoelastic haemostatic tests studies have often indicated a hypercoagulative test signal with citrated blood, which could influence clinical decision makings. PURPOSE: The aim of this study was to compare fresh and citrated whole blood using two non-automated viscoelastic ROTEM and Sonoclot tests. Our hypothesis was that citrated blood would demonstrate a hypercoagulative response in this setting, not tested before. METHODS: Perioperative viscoelastic coagulation changes were evaluated with a ROTEM and Sonoclot in 38 patients undergoing elective brain tumor surgery. The citrated samples were recalcified with CaCl2. Wilcoxon nonparametric-paired tests and Bland-Altman plots were performed to compare the fresh and citrated blood analyses. RESULTS: The citrated blood showed a hypercoagulative response in ROTEM NATEM-clot formation time and α-angle, Sonoclot-clot rate and platelet function, as compared to fresh blood (p<0.0001). CONCLUSIONS: Fresh whole blood may theoretically reflect in vivo haemostasis more closely than citrated analyses, which indicated a hypercoagulative response as compared to the fresh whole blood analyses Bland-Altman plots also indicated that ROTEM reference ranges in patients undergoing brain surgery should be redefined. Future studies must establish the correlation between viscoelastic test results using fresh or citrate anticoagulated blood and clinical outcomes, such as bleeding, transfusion or reoperation for postoperative haematoma.