Activated Clotting Time Research Articles

Post-Neutralisation Activated Clotting Time and Postoperative Transfusions in Cardiac Surgery Outcome.

To assess the impact of post-protamine neutralisation activated clotting time (ACT) values on postoperative outcomes including chest drain output, transfusion requirements, and CICU stay, in patients undergoing cardiac surgery. Observational comparative study. Place and Duration of the Study: Department of Anaesthesiology, The Aga Khan University Hospital, Karachi, Pakistan, from February to August 2023. Ethical approval was obtained to collect data from elective cardiac surgery patients' charts. A sequential sampling approach analysed the baseline and post-protamine neutralisation ACT values, categorising patients into two groups. Group A maintained ACT within 10% of baseline, while Group B deviated. The outcomes measured included transfusion needs, chest drain output, additional protamine, cardiac intensive care unit (CICU) stay, and postoperative reopening. Statistical analysis included mean, median, frequency, t-test / Mann-Whitney U test, and Chi-square test. The study comprised 101 patients (39 in Group A, 62 in Group B), with similar baseline health. No significant differences were found in tranexamic acid use, CICU stay, chest drain output, or transfusion rates between the groups (p >0.05). Maintaining ACT within 10% of baseline post-protamine neutralisation results in similar intraoperative and postoperative outcomes, suggesting potential benefits in avoiding the aggressive protamine therapy and ensuring haemostasis in cardiac surgery. Coronary Artery bypass grafting, Cardiopulmonary bypass, Activated clotting time (ACT), Heparin, Postoperative bleeding, Blood transfusions.

Post-Neutralisation Activated Clotting Time and Postoperative Transfusions in Cardiac Surgery Outcome.

To assess the impact of post-protamine neutralisation activated clotting time (ACT) values on postoperative outcomes including chest drain output, transfusion requirements, and CICU stay, in patients undergoing cardiac surgery. Observational comparative study. Place and Duration of the Study: Department of Anaesthesiology, The Aga Khan University Hospital, Karachi, Pakistan, from February to August 2023. Ethical approval was obtained to collect data from elective cardiac surgery patients' charts. A sequential sampling approach analysed the baseline and post-protamine neutralisation ACT values, categorising patients into two groups. Group A maintained ACT within 10% of baseline, while Group B deviated. The outcomes measured included transfusion needs, chest drain output, additional protamine, cardiac intensive care unit (CICU) stay, and postoperative reopening. Statistical analysis included mean, median, frequency, t-test / Mann-Whitney U test, and Chi-square test. The study comprised 101 patients (39 in Group A, 62 in Group B), with similar baseline health. No significant differences were found in tranexamic acid use, CICU stay, chest drain output, or transfusion rates between the groups (p >0.05). Maintaining ACT within 10% of baseline post-protamine neutralisation results in similar intraoperative and postoperative outcomes, suggesting potential benefits in avoiding the aggressive protamine therapy and ensuring haemostasis in cardiac surgery. Coronary Artery bypass grafting, Cardiopulmonary bypass, Activated clotting time (ACT), Heparin, Postoperative bleeding, Blood transfusions.

European practices on antithrombotic management during percutaneous mechanical circulatory support in adults: insights from an international survey

Abstract Background Bleeding and thrombotic complications remain a major concern in cardiogenic shock (CS) patients undergoing percutaneous mechanical circulatory support (pMCS) with veno-arterial extracorporeal membrane oxygenation (V-A ECMO) and/or microaxial flow pumps like the Impella. Antithrombotic practices strongly determine the coagulopathic risk, but standardized protocols are lacking in this context. Purpose This survey outlines European practices on antithrombotic management in adults on pMCS for CS, making an initial effort to standardize practices, inform future trials, and enhance outcomes. Methods This online cross-sectional survey was distributed through digital newsletters and social media platforms by the Association of Acute Cardiovascular Care (ACVC) of the ESC and the European branch of the Extracorporeal Life Support Organization (EuroELSO). The survey was accessible from April 17th to May 23rd, 2023. The target population were European clinicians involved in care for adults on pMCS. Results We included 105 responses from 26 European countries. In 72.4% of the European respondents’ institutions, a standardized local anticoagulation protocol is present, with unfractionated heparin (UFH) being the predominantly used anticoagulant (Impella: 97.0%; V-A ECMO: 96.1%). Similarly, the purge solution during Impella support is most frequently UFH-based (84.1%). A bicarbonate-based purge solution (BBPS) as standard purge is reported by only 1.6%. UFH titration based on the activated partial thromboplastin time (APTT) alone is the most common practice either for Impella (43.1%) and for V-A ECMO (32.9%). A minority of 16.9% and 13.2% indicate relying on activated clotting time (ACT) for UFH-titration during Impella and V-A ECMO support, respectively. UFH-titration protocols are anti-Xa based for 12.3% (Impella) and 10.5% (V-A ECMO) of the respondents. An UFH anticoagulant protocol based on APTT and anti-Xa in parallel is the preferred option for 10.8% (Impella) and 14.5% (V-A ECMO) of the respondents. Anticoagulant targets for APTT, ACT and anti-Xa varied across institutions. The majority (83.8%) does not alter their anticoagulation management in case of combined Impella plus V-A ECMO-approach (ECMELLA). Typical thresholds for transfusion or administration of blood products without acute bleeding as indication vary substantially and are frequently not predefined. Following acute coronary syndrome without percutaneous coronary intervention (PCI), 54.0% and 42.7% administered dual antiplatelet therapy during Impella and V-A ECMO support, increasing to 93.7% and 84.0% after PCI. Conclusions Our survey validated the considerable variation in antithrombotic management in adults in CS on pMCS across European centres. There is a pressing demand for a standardized approach to antithrombotic management in this context to mitigate the impact of coagulopathic complications and, consequently, enhance outcomes.Figure 1.Figure 2.

Heparin reversal for coronary artery perforation

Abstract Background/Introduction In the management of coronary artery perforation (CAP) during percutaneous coronary intervention (PCI), heparin reversal can provide hemostatic effects but raises concerns about potential coronary thrombosis if an intracoronary artery guidewire or balloon is in place. Purpose We aimed to evaluate the safety and efficacy of heparin reversal during device insertion for CAP. We also aimed to determine the optimal target activated clotting time (ACT) to maintain when performing heparin reversal. Methods We analyzed cases of CAP which occurred during PCI procedures in a single center from January 2006 to October 2023. Patients were assigned to two groups according to whether they received heparin reversal with a device in place. The safety outcome was the periprocedural myocardial infarction (creatine kinase-MB >5 times the upper normal limit), and the efficacy outcome was successful hemostasis at the end of the procedures (complete absence of CAP on angiography). Results Among the 22,368 cases, 368 (1.6%) developed CAP, consisting of main vessels 45%, distal vessels 43%, and collateral vessels 12%. Heparin reversal with a device in place was implemented in 211 (57%) cases. Of these, 16 (7.6%) experienced coronary thrombosis. After adjusting covariates by the multivariable logistic regression model, heparin reversal with a device in place was significantly associated with a higher incidence of periprocedural myocardial infarction (11% vs 4.5%; adjusted OR: 3.11; 95% CI: 1.24–7.78; P = 0.015) and a higher rate of successful hemostasis (91% vs 73%; adjusted OR: 2.78; 95% CI: 1.27–6.09; P = 0.011). In the analysis of cases where minimum ACT value was available (n = 251), this value was significantly correlated with coronary thrombosis (r = −0.16, P = 0.012). When the cutoff values of minimum ACT were set at 200, 150, and 120 seconds as a binomial variable, the correlation coefficient was r = −0.08 (P = 0.158), r = −0.16 (P = 0.009), r = −0.20 (P = 0.001), respectively. Conclusions Heparin reversal after CAP with an intracoronary artery device in place was significantly associated with a higher incidence of periprocedural MI but also a higher rate of successful hemostasis. A minimum ACT value <150 seconds was significantly correlated with coronary thrombosis. These results propose a novel algorithm for CAP management strategies.Management algorithm for CAP

Lupus anticoagulant and valvular cardiac surgery.

Despite its name, lupus anticoagulant (LAC) neither exclusively occurs in lupus nor induces anticoagulation. It is an antiphospholipid antibody found in 2%-4% of the population that promotes clot formation by targeting phospholipid-protein complexes in cell membranes. However, in vitro, LAC exhibits paradoxical effects, prolonging clotting times in phospholipid-dependent assays such as Activated Partial Thromboplastin Time (APTT). This unpredictability extends to point-of-care tests like Activated Clotting Time (ACT), which are frequently used to monitor anticoagulation during cardiac surgeries involving cardiopulmonary bypass (CPB). High doses of unfractionated heparin (UFH) are administered in these procedures, but the presence of LAC complicates ACT measurements, creating challenges for both anesthesiologists and surgeons. This case report highlights the clinical implications of LAC in perioperative management, underscoring the difficulties in ensuring adequate anticoagulation during CPB.

Intraoperative Bleeding Model for Swine Gastric Endoscopic Submucosal Dissection Via Heparinization

Background: Living swine has a high degree of coagulation and aggregation, and training for managing intraoperative bleeding during endoscopic submucosal dissection (ESD) is unsatisfactory. This study aimed to identify the appropriate heparin dose in an intraoperative bleeding model and validate its applicability. Methods: First, we explored the dose of heparin required for a swine bleeding model in which the activated clotting time reached and maintained the upper limit of measurement (1500 s) after 10 min. Second, we compared intraoperative bleeding and hematoma frequency during ESD for 2 cm lesions between the heparinized bleeding model and control groups. Intraoperative bleeding was classified according to the Forrest classification. Results: The combination of a bolus (300 U/kg), continuous infusion (300 U/kg/h), and a bolus dose (150 U/kg) of heparin 10 min after the first infusion was identified as the dose of the bleeding model. Five ESDs were performed in each heparinized bleeding model and the control group. The median number of intraoperative bleeding was significantly higher in the heparinized model than in the control group (5 [interquartile range {IQR}, 4–7] vs. 3 [IQR, 0–4], p = 0.028). All intraoperative bleeding events were not spurting (Forrest Ia) but oozing (Forrest Ib). The median number of hematomas was significantly higher in the heparinized model group than in the control group (3 [IQR, 1–4] vs. 0 [IQR, 0–1], p = 0.023). Conclusion: High doses of heparin significantly increased intraoperative bleeding and hematoma during swine ESD.

Ability of Activated Clotting Time Measurements to Monitor Unfractionated Heparin Activity During NonCardiac Arterial Procedures

Activated clotting time (ACT) measurements are frequently used to monitor unfractionated heparin activity during non-cardiac arterial procedures (NCAP). Accuracy of ACT-guided heparinization is mandatory to prevent heparin under- and overdosing, thereby minimizing thrombo-embolic complications (TEC) and bleeding risk. The main objective of this study was to investigate accuracy of ACT to monitor heparin activity during NCAP using the Hemostasis Management System Plus with high-range cartridges. ACT values were compared with anti-Xa measurements, regarded as the standard test to measure active heparin. This was a single centre, prospective, observational cohort study. Perioperative blood samples of patients undergoing NCAP between December 2022 and September 2023 were used to perform bedside ACT measurements and anti-Xa assays in the clinical laboratory. Primary outcome was correlation between ACT and anti-Xa measurements. TEC, mortality and bleeding complications within 30 days postoperatively or during primary admission were also scored. 196 pairs of ACT and anti-Xa measurements were performed in 34 patients. Strong correlation was observed between anti-Xa and ACT measurements (Pearson correlation coefficient = 0.84, 95% CI = 0.79 - 0.87, p < 0.001). Apart from anti-Xa, no additional variables were associated with ACT in multivariate linear regression analyses (regression coefficient β = 36.7, 95% CI = 33.3 - 40.1, p < 0.001). Bleeding complications occurred in 29% of the patients, while both TEC and mortality were observed in one patient. strong correlation and an independent association were observed between heparin activity measured by anti-Xa and ACT using the Hemostasis Management System Plus.

Bivalirudin anticoagulation for an infant with heparin resistance on ECMO: A case report.

Extracorporeal membrane oxygenation (ECMO) technology in the field of intense care for children in China has developed rapidly, and it has become a key strategy for the rescue treatment of critically ill children and an advanced extracorporeal life support system. Compared with adults and children, neonatal respiratory disease with ECMO support has the best prognosis, with an average survival rate of 74%. Bleeding and thrombotic events during ECMO are common, morbid, and potentially lethal. Therefore, how to balance the coagulation state is the key to ECMO management. A full-term male infant (2h 5min) was hospitalized for respiratory distress and cyanosis. With a history of premature rupture of membranes (>7 hours) and a birth weight of 3000 g, the patient had Apgar scores of 7, 8, and 9 at 1, 5, and 10 minutes, respectively. This infant has the indication of extracorporeal membrane lung support. After full communication, venoarterial-ECMO was performed, and intravenous infusion of heparin was used for anticoagulation management. We encountered an unreliable heparin monitoring in an infant on ECMO, which considered as heparin resistance. Subsequently, we switched the anticoagulant from heparin to bivalirudin and managed by using multiple laboratory tests including activated clotting time (ACT) and activated partial thromboplastin time. The phenomenon of inconsistent monitoring results occurred later. To help the clinic to adjust the anticoagulation dose accurately, we adopted additional tests such as thrombin-antithrombin complex (TAT) and fibrin/fibrinogen degradation products and applied comparison of thrombela stogram (TEG)-ACT with anticoagulated specimens and bedside non-anticoagulated ACT, then recommended clinicians to use activated partial thromboplastin time combined with TAT. In collaboration with other symptomatic supportive treatments, the ECMO flow was gradually reduced, the respiratory and circulatory functions were stable after reducing the flow rate, there was no bleeding tendency, and the ECMO was finally evacuated. Due to the unique physiological characteristics of newborns, the hemostatic changes differ significantly from those in adults. Precise monitoring of anticoagulation becomes a critical and challenging task. Bivalirudin can be effectively used for anticoagulation management in neonatal ECMO; however, due to its unique characteristics, precise dose adjustment poses a challenge. Selecting the optimal laboratory monitoring indicators is crucial in this regard. In some cases, bedside ACT may not be the optimal anticoagulation monitoring parameter, and when necessary, comparative analysis can be conducted using anticoagulant-sample ACTs such as thrombela stogram-ACT. Traditional markers such as D-dimer/fibrinogen degradation products and newer indicators like TAT can reflect the activation of coagulation and assist in monitoring the anticoagulation effect, especially when there is conflicting information among the monitoring parameters.

Association Between Cerebral Microbleeds and Neurological Outcomes in Patients Who Underwent Extracorporeal Membrane Oxygenation.

Cerebral microbleeds (CMBs) are common and varied in patients receiving extracorporeal membrane oxygenation (ECMO). Here, the authors describe CMB findings in patients receiving ECMO and their association with clinical factors. A total of 138 patients receiving ECMO were enrolled and categorized as venovenous and venoarterial. Blood coagulation profiles during ECMO support and Glasgow Coma Scale (GCS) scores within 7 days were recorded. Patients with CMBs exhibited prolonged activated clotting time (P<0.001), decreased fibrinogen levels (P<0.001), reduced platelet counts (P<0.001), and extended prothrombin time (P<0.001). A significant correlation (P<0.05) was observed between the presence of CMBs and most coagulation parameters among all patients. Patients with venoarterial ECMO had significantly higher activated partial thromboplastin time, activated clotting time, and prothrombin time compared with those with venovenous ECMO (all P<0.05). Patients with a less severe CMB burden exhibited higher GCS scores and better neurological injury outcomes at both 7 and 90 days. CMB burden in all patients with ECMO was significantly correlated (P<0.05) with most blood coagulation profiles and neurological injury. CMB burdens after ECMO are common, varied, and associated with a variety of clinical conditions. These findings may guide ECMO management.

Protamine Dosing for Heparin Reversal Following Cardiopulmonary Bypass: A Double-Blinded Prospective Randomized Control Trial Comparing Two Strategies.

Drug shortages are a frequent challenge in current clinical practice. Certain drugs, (e.g., protamine) lack alternatives and inadequate supplies can limit access to services. Conventional protamine dosing uses heparin ratio-based calculations for heparin reversal following CPB and may result in excess protamine utilization, and potential harm due to its intrinsic anticoagulation. We hypothesized that a fixed 250-mg protamine dose would be comparable, as measured by the activated clotting time, to a 1:1 (1 mg for every 100 U) protamine to heparin ratio-based strategy for heparin reversal and that protamine would be conserved. In a single-center, double-blinded trial, consenting elective adult cardiac surgical patients without pre-existing coagulopathy or ongoing anticoagulation, and a calculated initial heparin dose of ≥ 27500 U were randomized to receive, following CPB, protamine as a fixed dose (250 mg) or a ratio-based dose (1 mg:100 U heparin). The primary outcome was the activated clotting time following initial protamine administration, assessed by Student's t-test. Secondary outcomes included total protamine, the need for additional protamine, and the cumulative 24-h chest tube output. There were 62 and 63 patients in the fixed- and ratio-based dose groups, respectively. The mean post-protamine ACT was not different between groups (-2.0 s, 95% CI -7.2 to 3.3 s, P = 0.47). Less total protamine per case was administered in the fixed-dose group (2.1 50-mg vials, 95% CI -2.4 to -1.8, P < 0.0001). There was no difference in the cumulative 24-h chest tube output (difference = -77 ml, 95% CI 220 to 65 ml, P = 0.28). A 1: 1 heparin ratio-based protamine dosing strategy compared to a fixed 250-mg dose resulted in the administration of a larger total dose of protamine no difference in either the initial ACT or the amount postoperative chest-tube bleeding.

CytoSorb hemoadsorption of apixaban during cardio-pulmonary bypass for heart transplantation

IntroductionHeart transplantation is an emergency surgery requiring cardio-pulmonary bypass (CPB) and its timing is unpredictable. Patients on the transplant waiting list often have multiple reasons for being anticoagulated. Direct oral anticoagulants (DOACs) such as apixaban are very popular due to their well-known advantages. Intraoperative removal of apixaban using CytoSorb® (CytoSorbents Inc., Princeton, NJ, USA), seems to be an interesting solution for patients on DOACs requiring an emergency CPB intervention. The aim of this short communication is to describe the perioperative effects of the use of the CytoSorb® hemoadsorption device during emergency CPB for a heart transplant patient Case presentationA 61-year-old male patient (75kg/173cm) wait-listed for heart transplantation was admitted to our hospital (Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France) to benefit from a heart transplantation. This patient, with many comorbidities, has an end-stage heart failure with multiple episodes of decompensation over the previous year. He was anticoagulated with a Vitamin K antagonist (VKA) due to atrial fibrillation and was switched to apixaban (5mg twice daily) 9 days before surgery based on poor clotting control. A NaCl 0.9% primed CytoSorb cartridge was inserted into the CPB circuit. Hemoadsorption was performed during the entire CPB duration. Anti-Factor Xa Activity (AFXaA) levels were taken at multiple time points before, during and after surgery in order to monitor anticoagulation. Results. Preoperatively, activated Clotting Time (ACT) was 146 seconds. The ACT reached 545 seconds after administration of 25,000IU of unfractionated heparin (UFH). Surgery consisted of an orthotopic heart transplantation with bi-caval anastomoses.CPB duration was 133 minutes with 83 minutes of aortic cross clamping. Total graft ischemic time was 249 minutes. At the time of anesthesia induction and after UFH administration, AFXaA levels were 330ng/mL and 317ng/mL, respectively. Thereafter, AFXaA decreased to 137ng/mL during CPB and to 57ng/mL after the end of CPB and 250mg (=25,000IU) of protamine administration.After surgery, AFXaA levels stabilized over 50ng/mL over the next 14 hours. Postoperative anticoagulation was performed with the use of UFH starting 6 hours after surgery.No primary graft dysfunction (PGD) was observed, and during the post-operative period of 72 hours, the patient did not have any bleeding events requiring reintervention or transfusion. ConclusionIn conclusion, we observed that CytoSorb® could be a potential solution to remove apixaban intraoperatively. If this efficacy is confirmed in larger trials, it would allow transplant candidates to be treated with DOACs without requiring a switch to VKAs.

Molecular Biomarkers for In Vitro Thrombogenicity Assessment of Medical Device Materials.

To develop standardized in vitro thrombogenicity test methods for evaluating medical device materials, three platelet activation biomarkers, beta-thromboglobulin (β-TG), platelet factor 4 (PF4), soluble p-selectin (CD62P), and a plasma coagulation marker, thrombin-antithrombin complex (TAT), were investigated. Whole blood, drawn from six healthy human volunteers into Anticoagulant Citrate Dextrose Solution A was recalcified and heparinized over a concentration range of 0.5-1.5 U/mL. The blood was incubated with test materials with different thrombogenic potentials for 60 min at 37°C, using a 6 cm2/mL material surface area to blood volume ratio. After incubation, the blood platelet count was measured before centrifuging the blood to prepare platelet-poor plasma (PPP) and platelet-free plasma (PFP) for enzyme-linked immunosorbent assay analysis of the biomarkers. The results show that all four markers effectively differentiated the materials with different thrombogenic potentials at heparin concentrations from 1.0 to 1.5 U/mL. When a donor-specific heparin concentration (determined by activated clotting time) was used, the markers were able to differentiate materials consistently for blood from all the donors. Additionally, using PFP instead of PPP further improved the test method's ability to differentiate the thrombogenic materials from the negative control for β-TG and TAT. Moreover, the platelet activation markers were able to detect reversible platelet activation induced by adenosine diphosphate (ADP). In summary, all three platelet activation markers (β-TG, PF4, and CD62P) can distinguish thrombogenic potentials of different materials and detect ADP-induced reversible platelet activation. Test consistency and sensitivity can be enhanced by using a donor-specific heparin concentration and PFP. The same test conditions are applicable to the measurement of coagulation marker TAT.

Systematic review of clinical guidelines and consensus statements concerning heparin and protamine dosing and monitoring of anticoagulation levels for non-cardiac arterial procedures.

This systematic review was performed to examine all published practice Guidelines and Consensus Statements (together: GCS) on heparin dosing and monitoring during non-cardiac arterial procedures (NCAP). The objective was to scrutinize the recommendations and advice outlined within these GCS documents and to evaluate the supporting evidence for these recommendations. Additionally, the use of the activated clotting time (ACT) and target ACT values were explored. This systematic review was performed in accordance with the PRISMA Guidelines. Medline and Embase databases were searched to identify all GCSs in the English language on NCAP. The final literature search was performed in January 2023. This search was supplemented by searching websites of relevant professional vascular surgical organizations for GCSs. Titles and abstracts were assessed by two independent reviewers. Of 9716 titles identified, 27 GCSs met the predefined inclusion criteria: six GCSs regarding carotid intervention, seven regarding procedures for aneurysmal disease of the abdominal aorta and iliac arteries, 12 regarding interventions for acute and chronic peripheral arterial occlusive disease and two regarding open and endovascular interventions of thoraco-abdominal aortic aneurysms. Administration of heparin is advised for al NCAP. There was high variability concerning heparin dose: both standard dose as weight based dosing (30-150 IU/kg) was advised. Recommendations on repeated doses, ACT monitoring and heparin reversal using protamine also varied widely. In none of the GCSs, the type of the ACT measuring device or used cartridges were specified. Large variability was found between the included GCSs with regard to the recommendations on heparin dose and target ACT values during NCAP. Advice and recommendations in GCSs were based on low-quality studies or without providing any reference at all. The described variability in recommendations emphasizes the need for large prospective (randomized) studies or the incorporation of data on heparin and the use of ACT monitoring into verified vascular surgery registries, to develop evidence-based, practical and uniform applicable recommendations.

Anticoagulation management for cardiopulmonary bypass using TEG® 6 s in a patient receiving both heparin and dabigatran

BackgroundIt is difficult to evaluate adequate dose of heparin for cardiopulmonary bypass (CPB) by activated clotting time (ACT) in a patient receiving both heparin and dabigatran because dabigatran can also prolong ACT. We evaluated the effect of dabigatran by thromboelastography (TEG) to determine adequate heparin dose for CPB.Case presentationAn 81-year-old woman receiving both heparin and dabigatran was scheduled for an emergency surgical repair of iatrogenic atrial septal perforation. Although ACT was prolonged to 419 s, we performed TEG to distinguish anticoagulation by dabigatran from heparin comparing R in CK and CHK. As the results of TEG indicated residual effect of dabigatran, we reversed dabigatran by idarucizumab and then dosed 200 U/kg of heparin to achieve adequate anticoagulation for CPB by heparin.ConclusionsTEG could help physicians to determine need for idarucizumab and also an adequate dose of heparin to establish appropriate anticoagulation for CPB.

Peak Procedural ACT Is Associated With All-Cause Mortality After Femoral Access PCI

BackgroundA minimum threshold activated clotting time (ACT) to guide heparin dosing during percutaneous coronary intervention (PCI) is associated with lower ischemic complications. However, data are variable regarding the risk of high ACT levels. The aim of this study was to assess the impact of peak procedural ACT on complications and mortality for transfemoral and transradial access PCI. MethodsThe UC San Diego Health National Cardiovascular Data Registry CathPCI Registry was used to obtain data on patients who underwent native vessel PCI from January 2007 to September 2022. Coronary artery bypass graft patients and those who received bivalirudin were excluded. Complications and all-cause mortality at 30 days and 1-year post-PCI were assessed by ACT tertile. ResultsA total of 2473 patients (age 65 ± 12 years; 74% male) undergoing PCI with 53% femoral and 47% radial access were included. The majority (82%) had 1-vessel coronary artery disease with heterogeneous clinical presentations (21.8% ST-elevation myocardial infarction, 25.4% non–ST-elevation myocardial infarction, 4.9% unstable angina, 33.8% stable angina, 3.4% atypical chest pain, 10.7% other indication for PCI). With femoral access, patients in the third tertile (ACT ≥ 275) had significantly higher all-cause mortality at 30 days (5.3% vs 2.7% vs 0.9%; P < .001), 6 months (6.3% vs 4.0% vs 2.0%; P = .007), and 1 year (9.0% vs 6.0% vs 2.7%; P < .001) compared to the second (ACT 228-275) and first tertile (ACT ≤ 228), respectively. A 30-day landmark analysis revealed that there was no difference in all-cause mortality beyond 30 days (3.9% vs 3.4% vs 1.8%; P = .176). There were increased bleeding complications in the highest tertile (12.8% vs 9.8% vs 7.5%; P = .034) and a higher need for blood products (10.4% vs 6.7% vs 5.4%; P = .014). There was no difference in ischemic major adverse cardiovascular events specifically periprocedural myocardial infarction or stroke between tertiles. There was no difference in clinical outcomes by peak ACT for patients who had radial access. ConclusionsHigher ACT with transfemoral access PCI was associated with increased 30-day mortality, bleeding complications, and need for blood products post-PCI.

Association of ACT-guided anticoagulation with complications during ECMO support: A systematic review and meta-analysis: ACT monitoring and haemostatic complications during ECMO

ObjectiveExtracorporeal membrane oxygenation (ECMO) requires systemic anticoagulation to reduce the risk of thromboembolic events. Despite its historic role, activated clotting time (ACT) remains a widely used heparin monitoring method. Systematic evidence on the association of ACT-guided monitoring with hemorrhagic or thromboembolic complications does not exist. DesignSystematic literature review and meta-analysis (Scopus and PubMed, July 2023) SettingAll cohort studies ParticipantsPatients receiving ECMO support InterventionAnticoagulation monitoring with ACT Measurements and maim resultsWe identified 3177 publications, with eight studies reporting the average ACT values for patients with and without bleeding. Meta-analysis revealed no significant difference in the compared groups (SMD = 0.69; 95% CI: −0.05; 1.43, p = 0.069; I2 = 87.4%). Three studies (n = 117 patients) reported on the average ACT values for patients with thrombosis, without significant differences in ACT values between patients with and without thrombosis (SMD = 0.47; 95% CI: −0.50; 1.44, p = 0.342; I2 = 81.1%). ConclusionsEven though ACT is a widely used heparin monitoring tool, the evidence on its association with hemorrhagic or thromboembolic events is still controversial and limited. Further studies are essential to elucidate the role of ACT in anticoagulation monitoring during ECMO support.

Handheld point-of-care devices for snakebite coagulopathy: a scoping review.

Venom induced consumption coagulopathy (VICC) is a common complication of snakebite that is associated with hypofibrinogenaemia, bleeding, disability, and death. In remote tropical settings, where most snakebites occur, the 20-minute whole blood clotting test is used to diagnose VICC. Point-of-care (POC) coagulation devices could provide an accessible means of detecting VICC that is better standardised, quantifiable, and more accurate. In this scoping review, the mechanistic reasons that previously studied POC devices have failed in VICC are considered, and evidence-based recommendations are made to prioritise certain devices for clinical validation studies. Four small studies have evaluated a POC international normalised ratio (INR) device in patients with Australian Elapid, Daboia russelii and Echis carinatus envenoming. All of these studies used POC INR devices that rely on a thrombin substrate endpoint, which, unlike laboratory-based INR measurement, is known to underestimate INR in patients with hypofibrinogenaemia. Seventeen commercially available POC devices for measuring INR, activated clotting time (ACT), activated partial thromboplastin time (aPTT), fibrinogen, D-dimer, and fibrin(ogen) degradation products (FDP) have been reviewed. POC INR devices that detect fibrin clot formation, as well as a novel POC device that quantifies fibrinogen were identified, that show promise for use in patients with VICC. These devices could support more accurate allocation of antivenom, reduce the time to antivenom administration, and provide improved clinical trial outcome measurement instruments. There is an urgent need for these promising POC coagulation devices to be validated in prospective clinical snakebite studies.

Relation between antithrombin-III activity and activated clotting time for cardiopulmonary bypass.

Heparin resistance (HR) is observed before cardiopulmonary bypass (CPB), despite with normal antithrombin III (AT-III) levels. The relationships between preoperative AT-III activity and activated clotting time (ACT) after the first heparin dose should be clarified. We retrospectively analyzed the data of 818 patients who underwent CPB surgery, with the initial heparin of 300, 400, and 500IU/kg, between 2017 and 2021. We defined HR as the failure to achieve ACT after the initial heparin dose (Post ACT) of > 480s.There were no significant correlations between the AT-III activity and Post ACT in all patients, including 143 patients with AT-III activity < 80% and 675 patients with AT-III activity of ≥ 80%. Also, there were no significant correlations between the AT-III activity and Post ACT in 74 patients who received heparin of 300IU/kg, in 186 patients with 400IU/kg, and in 339 patients with 500IU/kg. After identifying smoking, HR, activated partial thromboplastin time, fibrinogen degradation products (FDP), and ACT as influencing factors, multiple comparisons using the Steel-Dwass test showed significant difference in FDP and HR among the patients who received heparin of 300IU/kg, 400IU/kg, and 500IU/kg. There is no association between preoperative AT-III activity and ACT after the first heparin administration for CPB, even in different dose of heparin. Rather, the higher the initial UFH dose is, the higher ACT may be, regardless of the AT-III activity.

Anticoagulation Monitoring Using Activated Clotting Time in Patients Receiving Extracorporeal Membrane Oxygenation: A Meta-Analysis of Correlation Coefficients

ObjectiveExtracorporeal membrane oxygenation (ECMO) requires systemic anticoagulation to maintain the circuit patency. However, the use of anticoagulation carries a risk of severe haemorrhage, necessitating rigorous monitoring. Activated clotting time (ACT) is a widely used monitoring tool, however the evidence on its correlation with unfractionated heparin (UFH) infusion dose is limited. Therefore, we aimed to analyse the correlation between ACT and UFH infusion during ECMO. DesignSystematic literature review and meta-analysis of correlation coefficients (Scopus and PubMed, up to July 13, 2024). PROSPERO: CRD42023448888 SettingAll retrospective and prospective studies ParticipantsPatients receiving ECMO support InterventionAnticoagulation monitoring during ECMO support Measurements and maim resultsNineteen studies were included in the analysis, and the meta-analysis encompassed 16. The vast majority of authors (n = 16) found a weak correlation, and none reported a strong correlation between ACT and UFH infusion dose. The meta-analysis (n = 12625 samples) identified a weak correlation, with the pooled estimate of correlation coefficients being 0.132 (95% CI 0.03; 0.23). Lastly, the most common adverse events were haemorrhage (pooled 45%) and thrombosis (30%), and 47% of patients died during the hospital stay. ConclusionsDespite ACT being a widely used UFH monitoring tool in ECMO patients, our meta-analysis found a weak correlation between ACT and UFH infusion dose. New trials are required to investigate the role of emerging tools and to clarify the most appropriate monitoring strategy for patients receiving ECMO support.

Intracardiac ultrasound-guided transseptal puncture in horses: Outcome, follow-up, and perioperative anticoagulant treatment.

Cardiac catheterizations in horses are mainly performed in the right heart, as access to the left heart traditionally requires an arterial approach. Transseptal puncture (TSP) has been adapted for horses but data on follow-up and closure of the iatrogenic atrial septal defect (iASD) are lacking. To perform TSP and assess postoperative complications and iASD closure over a minimum of 4 weeks. Eleven healthy adult horses. Transseptal puncture was performed under general anesthesia. Serum cardiac troponin I concentrations were measured before and after puncture. Weekly, iASD closure was monitored using transthoracic and intracardiac echocardiography. Relationship between activated clotting time and anti-factor Xa activity during postoperative enoxaparin treatment was assessed in vitro and in vivo. Transseptal puncture was successfully achieved in all horses within a median duration of 22 (range, 10-104) minutes. Balloon dilatation of the puncture site for sheath advancement was needed in 4 horses. Atrial arrhythmias occurred in 9/11 horses, including atrial premature depolarizations (N = 1), atrial tachycardia (N = 5), and fibrillation (N = 3). Serum cardiac troponin I concentrations increased after TSP, but remained under the reference value in 10/11 horses. Median time to iASD closure was 14 (1-35) days. Activated clotting time correlated with anti-factor Xa activity in vitro but not in vivo. Transseptal puncture was successfully performed in all horses. The technique was safe and spontaneous iASD closure occurred in all horses. Clinical application of TSP will allow characterization and treatment of left-sided arrhythmias in horses.