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 500 IU/kg, between 2017 and 2021. We defined HR as the failure to achieve ACT after the initial heparin dose (Post ACT) of > 480 s.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 300 IU/kg, in 186 patients with 400 IU/kg, and in 339 patients with 500 IU/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 300 IU/kg, 400 IU/kg, and 500 IU/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.

A COVID-19 case report with low ACT(activated clotting time) and high serum D-dimer level: Antithrombin III deficiency?

The Coronavirus Disease 2019 (COVID-19), caused by the virus named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is a global public health problem in which atypical findings other than the usual fever and respiratory symptoms render early diagnosis and treatment difficult. Cases with atypical clinical and laboratory presentations continue to pose a challenge in the treatment and control of the disease. This case report aims to share our follow-up and treatment experience in a patient considered to have antithrombin III (ATIII) deficiency based on activated clotting time (ACT) levels unresponsive to heparin who was admitted to intensive care unit due to COVID-19-induced cytokine storm associated with extreme D-dimer elevation (>65,000 µg/L).

Glass bead-activated clotting time (gb-ACT) for monitoring the anticoagulation effects in elderly patients with high risk of venous thromboembolism (VTE).

BACKGROUND: To find a new bedside method to monitor the anticoagulation effects of low-molecular-weight heparins (LMWHs) in patients with a high risk of venous thromboembolism (VTE). RESEARCH DESIGN AND METHODS: A total of 32 hospitalized patients (aged ≥60 years) who were at high risk of VTE were assigned to receive subcutaneous LMWH for 5 to 14 days. Plasma anti-factor Xa (anti-Xa) activity was conducted by a chromogenic method, and the glass bead-activated whole blood clotting time (gb-ACT) value was obtained by a Sonoclot Analyzer. RESULTS: A correlation between the gb-ACT values and the anti-Xa levels was suggested (R = 0.447, p = 0.002), and it was stronger in the older group aged 80 years above (R = 0.467, p = 0.008) and in the group of patients with an eGFR of 30 ~ 60 mL/min (R = 0.565, p = 0.005). The area under the curve (AUC) for gb-ACT by receiver operating characteristic (ROC) curve evaluation was 0.725 (p = 0.011), and the gb-ACT >282.5s provided a sensitivity of 60% and specificity of 74% for anti-Xa >0.800 IU/ml. CONCLUSIONS: The gb-ACT values detected by a Sonoclot Analyzer could act as a novel bedside method in the monitoring of LMWH anticoagulation.

Activated clotting time value as an independent predictor of postoperative bleeding and transfusion.

OBJECTIVES: Activated clotting time (ACT) is commonly used to monitor anticoagulation during cardiac surgeries. Final ACT values may be essential to predict postoperative bleeding and transfusions, although ideal values remain unknown. Our aim was to evaluate the utility of ACT as a predictor of postoperative bleeding and transfusion use. METHODS: Retrospective study (722 patients) submitted to surgery between July 2018-October 2021. We compared patients with final ACT < basal ACT and final ACT ≥ basal ACT and final ACT < 140 s with ≥140 s. Continuous variables were analysed with the Wilcoxon rank-sum test; categorical variables using Chi-square or Fisher's exact test. A linear mixed regression model was used to analyse bleeding in patients with final ACT < 140 and ≥140. Independent variables were analysed with binary logistic regression models to investigate their association with bleeding and transfusion. RESULTS: Patients with final ACT ≥ 140 s presented higher postoperative bleeding than final ACT < 140 s at 12 h (P = 0.006) and 24 h (**P = 0.004). Cardiopulmonary bypass (CPB) time [odds ratio (OR) 1.009, 1.002-1.015, 95% confidence interval (CI)] and masculine sex (OR 2.842,1.721-4.821, 95% CI) were significant predictors of bleeding. Patients with final ACT ≥ 140 s had higher risk of UT (OR 1.81, 1.13-2.89, 95% CI; P = 0.0104), compared to final ACT < 140 s. CPB time (OR 1.019,1.012-1.026, 95% CI) and final ACT (OR 1.021,1.010-1.032, 95% CI) were significant predictors of transfusion. Female sex was a predictor of use of transfusion, with a probability for use of 27.23% (21.84-33.39%, 95% CI) in elective surgeries, and 60.38% (37.65-79.36%, 95% CI) in urgent surgeries, higher than in males. CONCLUSIONS: Final ACT has a good predictive value for the use of transfusion. Final ACT ≥ 140 s correlates with higher risk of transfusion and increased bleeding. The risk of bleeding and transfusion is higher with longer periods of CPB. Males have a higher risk of bleeding, but females have a higher risk of transfusion.

The imprecision of measuring activated clotting time (ACT) from the guiding catheter during percutaneous coronary interventions.

BACKGROUND: Finding the balance between the reduction in ischemic events and bleeding complications is crucial for the success of percutaneous coronary intervention (PCI). The activated clotting time (ACT) is used routinely worldwide to monitor and titrate anticoagulation therapy with unfractionated heparin (UFH) during the procedure. OBJECTIVES: We aimed to test the accuracy of ACT measurements from the guiding catheter compared to the arterial access sheath. METHODS: Patients undergoing PCI with UFH therapy were prospectively enrolled. Blood samples were drawn from the coronary guide catheter and the arterial access sheath. ACT values were determined in the same ACT machine, and potential interactions with clinical variables were analyzed. RESULTS: The study included 331 patients with post PCI ACT measurements. The mean ACT value of the catheter samples was statistically higher than the arterial access sample [294 ± 77 s Vs. 250 ± 60 s, p < 0.001]. The mean difference between the guiding catheter and the arterial line sheath samples was 43 ± 27 s (P < 0.001). We found that in 101/331 [30 %] patients the ACT from the guiding catheter was above 250 s, while from the access sheath it was below 250 s. Notably, in 40/331 [12 %] the ACT from the guiding catheter was above 200 s, while from the access sheath it was below 200 s. CONCLUSIONS: Large proportion of patient may be considered to have therapeutic ACT if measured from guide catheter during PCI, while the corresponding ACT from arterial sheath is subtherapeutic. This difference may have clinical and safety significance.

Activated clotting time-guided heparinization during open AAA surgery: a pilot study.

BACKGROUND: Arterial thrombo-embolic complications (TEC) are still common during and after non-cardiac arterial procedures (NCAP). While unfractionated heparin has been used during NCAP for more than 70 years to prevent TEC, there is no consensus regarding the optimal dosing strategy. The aim of this pilot study was to test the effectiveness and feasibility of an activated clotting time (ACT)-guided heparinization protocol during open abdominal aortic aneurysm (AAA) surgery, in anticipation of a randomized controlled trial (RCT) investigating if ACT-guided heparinization leads to better clinical outcomes compared to a single bolus of 5000 IU of heparin. METHODS: A prospective multicentre pilot study was performed. All patients undergoing elective open repair for an AAA (distal of the superior mesenteric artery) between March 2017 and January 2020 were included. Two heparin dosage protocols were compared: ACT-guided heparinization with an initial dose of 100 IU/kg versus a bolus of 5000 IU. The primary outcome was the effectiveness and feasibility of an ACT-guided heparinization protocol with an initial heparin dose of 100 IU/kg during open AAA surgery. Bleeding complications, TEC, and mortality were investigated for safety purposes. RESULTS: A total of 50 patients were included in the current study. Eighteen patients received a single dose of 5000 IU of heparin and 32 patients received 100 IU/kg of heparin with additional doses based on the ACT. All patients who received the 100 IU/kg dosing protocol reached the target ACT of > 200 s. In the 5000 IU group, TEC occurred in three patients (17%), versus three patients (9.4%) in the 100 IU/kg group. Bleeding complications were found in six patients (33%) in the 5000 IU group and in 9 patients (28%) in the 100 IU/kg group. No mortality occurred in either group. CONCLUSIONS: This pilot study demonstrated that ACT-guided heparinization with an initial dose of 100 IU/kg appears to be feasible and leads to adequate anticoagulation levels. Further randomized studies seem feasible and warranted to determine whether ACT-guided heparinization results in better outcomes after open AAA repair.

Mean Activated Clotting Time of Patients Receiving Intravenous Heparin and Undergoing Primary Percutaneous Coronary Intervention for ST Elevation Myocardial Infarction.

Introduction The most prevalent cause of death is acute myocardial infarction (AMI). Primary percutaneous coronary intervention (PPCI) has replaced thrombolysis as the recommended therapeutic option for individuals with ST-segment elevation myocardial infarction (STEMI). However, more effective anticoagulation regimes are required for PCI due to the limitations of unfractionated heparin. Objective This study aimed to ascertain the connection between the mean activated clotting time and the risk of bleeding and infarcts in individuals receiving intravenous heparin during PPCI for STEMI. Methods This was a one-year prospective observational study carried out at the National Institute of Cardiovascular Diseases (NICVD), Karachi, Pakistan. Results The majority (70.15%) were male, with a mean age of 56.08 ± 8.92 years. Following PPCI, the average active clotting time (ACT) was 350.56 ± 39.62 seconds (range 255 to 453), compared to the pre-PPCI mean of 504.15 ± 38.98 seconds. ACT was considerably higher in female patients, smokers, and overweight patients. The mean ACT was not significantly higher in patients with hypertension (HTN) and dyslipidemia (DLD). Conclusion The ACT range in this investigation was 255 to 453 seconds, and there was no discernible relationship between ACT readings and problems related to bleeding and ischemia. To determine who is more at risk, bleeding risk models should be used and improved further before catheterization.

Model construction and application for predicting pre-eclampsia by Sonoclot coagulation analyzer.

Maternal age has significantly increased among Chinese women, thereby posing risk of pregnancy-related complications. Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality, and coagulation analysis in conjunction with clinical signs and symptoms are generally used for its diagnosis with limited efficacy. Sonoclot coagulation analyzer is effective in assessing coagulation function used during cerebral surgery and cardiovascular surgery. However, its use has not been explored in preeclampsia. Here, we investigated the potential use of Sonoclot in diagnosing preeclampsia in obstetrics cases. Subjects meeting the screening criteria were divided either into a test group or a control group, according to whether they were preeclamptic or not. We recorded the Sonoclot-derived coagulation and the routine coagulation parameters including platelet function (PF), activated clotting time (ACT) and clot rate (CR), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB), and platelet count. Regression analysis was done on the relevant parameters to assess the feasibility of Sonoclot analyzer in preeclampsia diagnosis. In parallel, changes in preeclampsia lncRNAs was also evaluated. Significant differences were recorded in PT and ACT between the two groups. In the monovariant logistic regression, PT and ACT appeared to be reliable predictor variables. In the multinomial logistic regression, a total of five regression steps were performed with decreasing AIC values. The K-fold cross validation resulted in an accuracy rate (ACC) of 77.5%, a false positive rate of 16.4%, and a false negative rate of 33.2%. lncRNAs ANRIL and HOXD-AS1 were found deregulated. Our findings indicate that Sonoclot may be useful for diagnosis of preeclampsia in obstetrics.

Contributing factors to heparin resistance during cardiopulmonary bypass.

Since the risk factors for heparin resistance (HR) before cardiopulmonary bypass (CPB) have not been fully clarified, this study investigated the contributing factors for HR after the initial unfractionated heparin (UFH) dose of 500 IU/kg. We retrospectively analyzed the data of 371 patients who underwent CPB surgery, with the initial UFH dose of 500 IU/kg, between May 2017 and December 2021. We defined HR as the failure to achieve activated clotting time (ACT) of > 480 s after the initial UFH dose of 500 IU/kg. HR was observed in 36 patients (9.7%) (HR group), while HR was not observed in 335 patients (control group). The HR group included significantly more patients with preoperative use of UFH, with significantly higher white blood cell counts, fibrinogen, fibrinogen degradation products, D-dimer, and C-reactive protein, and lower hemoglobin and albumin. The multivariable logistic regression analysis identified albumin (OR: 3.09, 95% CI 1.3504-7.0845, p = 0.0075) and fibrinogen (OR: 0.99, 95% CI 0.9869-0.9963, p = 0.0003) as independent predictors for HR. Using the Youden index, the cutoffs of albumin and fibrinogen were calculated as 3.8 g/dL and 303 mg/dL, respectively. The receiver operating characteristic curves showed the predictive performance of albumin (area under the curve (AUC): 0.78, sensitivity: 65%, specificity: 81%) and fibrinogen (AUC: 0.77, sensitivity: 56%, specificity: 88%). The incidence of HR after the initial UFH dose of 500 IU/kg was 9.7%. The preoperative albumin < 3.8 g/dL and fibrinogen > 303 mg/dL were independent predictors for HR.

Anticoagulation Intensity during Appendage Occlusion: Lessons from Silent Cerebral Embolism.

INTRODUCTION: Endovascular left atrial appendage occlusion (LAAO) is associated with a high incidence of peri-procedure silent cerebral embolism (SCE), while the recommended activated clotting time (ACT) level by the expert consensus is lower than that in atrial fibrillation (AF) ablation. The aim of our study was to investigate whether raising the targeted ACT level during LAAO to the same level as AF ablation could decrease the incidence of SCE. METHODS: It was a prospective observational cohort study. Consecutive AF patients receiving LAAO between January 2021 and December 2022 were included and categorized into two groups based on the time of enrollment. Patients enrolled in 2021 (group 250) maintained a target ACT level of ≥250 s during LAAO procedure, while patients enrolled in 2022 (group 300) maintained the peri-procedure ACT ≥300 s. All patients underwent cerebral magnetic resonance imaging before and after the procedure. RESULTS: A total of 81 patients were included (38 in the group 250 and 43 in the group 300). After inverse probability of treatment weighting (IPTW), patients in the group 250 showed a significantly lower incidence of SCE than group 300 (IPTW p = 0.038). Only a stable high ACT pattern could decrease the risk of SCE. No significant differences were found between other ACT change patterns on the SCE incidence. CONCLUSION: Raising the peri-procedure ACT level to a stable 300 s could decrease the risk of the SCE without increasing the major bleeding events.

Comparison of Blood Concentration and Weight-Based Heparin and Protamine Dosing Strategies for Cardiopulmonary Bypass: A Systematic Review and Meta-Analysis.

BACKGROUND:  The conventional method of heparin and protamine management during cardiopulmonary bypass (CPB) is based on total body weight which fails to account for the heterogeneous response to heparin in each patient. On the other hand, the literature is inconclusive on whether individualized anticoagulation management based on real-time blood heparin concentration improves post-CBP outcomes. METHODS:  We searched databases of Medline, Excerpta Medica dataBASE (EMBASE), PubMed, Cumulative Index to Nursing and Allied Health Literature (CINHL), and Google Scholar, recruiting randomized controlled trials (RCTs) and prospective studies comparing the outcomes of dosing heparin and/or protamine based on measured heparin concentration versus patient's total body weight for CPB. Random effects meta-analyses and meta-regression were conducted to compare the outcome profiles. Primary endpoints include postoperative blood loss and the correlation with heparin and protamine doses, the reversal protamine and loading heparin dose ratio; secondary endpoints included postoperative platelet counts, antithrombin III, fibrinogen levels, activated prothrombin time (aPTT), incidences of heparin rebound, and re-exploration of chest wound for bleeding. RESULTS:  Twenty-six studies, including 22 RCTs and four prospective cohort studies involving 3,810 patients, were included. Compared to body weight-based dosing, patients of individualized, heparin concentration-based group had significantly lower postoperative blood loss (mean difference (MD)=49.51 mL, 95% confidence interval (CI): 5.33-93.71), lower protamine-to-heparin dosing ratio (MD=-0.20, 95% CI: -0.32 ~ -0.12), and higher early postoperative platelet counts (MD=8.83, 95% CI: 2.07-15.59). The total heparin doses and protamine reversal were identified as predictors of postoperative blood loss by meta-regression. CONCLUSIONS:  There was a significant correlation between the doses of heparin and protamine with postoperative blood loss; therefore, précised dosing of both could be critical for reducing bleeding and transfusion requirements. Data from the enrolled studies indicated that compared to conventional weight-based dosing, individualized, blood concentration-based heparin and protamine dosing may have outcome benefits reducing postoperative blood loss. The dosing calculation of heparin based on the assumption of a one-compartment pharmacokinetic/pharmacodynamic (PK/PD) model and linear relationship between the calculated dose and blood heparin concentration may be inaccurate. With the recent advancement of the technologies of machine learning, individualized, precision management of anticoagulation for CPB may be possible in the near future.

Investigation of real-world heparin resistance and anticoagulation management prior to cardiopulmonary bypass: report from a nationwide survey by the Japanese Association for Thoracic Surgery heparin resistance working group.

OBJECTIVE: Heparin resistance is often encountered during cardiopulmonary bypass. Heparin dose and activated clotting time target values for the initiation of cardiopulmonary bypass are not yet universally standardized; further no consensus exists on the management of heparin resistance. This study aimed to investigate the current real-world practice on heparin management and anticoagulant treatment for heparin resistance in Japan. METHODS: A questionnaire survey was conducted at medical institutions nationwide with which The Japanese Society of Extra-Corporeal Technology in Medicine members are affiliated, targeting surgical cases with cardiopulmonary bypass performed from January 2019 through December 2019. RESULTS: Among 69% (230/332) of the participating institutions, the criterion for heparin resistance was defined as "the target activated clotting time value not reached even with an additional dose of heparin administration". Cases of heparin resistance were reported in 89.8% (202/225) of the responded institutions. Of note, 75% (106/141) of the responded institutions reported heparin resistance associated with antithrombin activity ≥ 80%. Antithrombin concentrate was used in 38.4% (238/619 responses) or third dose of heparin in 37.8% (234/619 responses) for advanced heparin resistance treatment. Antithrombin concentrate was found to be effective in resolving heparin resistance in patients having normal, as well as lower antithrombin activity. CONCLUSION: Heparin resistance has occurred in many cardiovascular centers, even among patients with normal antithrombin activities. Interestingly, the administration of antithrombin concentrate resolved heparin resistance, regardless of the baseline antithrombin activity value.

Comparison of Rapid-, Kaolin-, and Native-TEG Parameters in Burn Patient Cohorts With Acute Burn-induced Coagulopathy and Abnormal Fibrinolytic Function.

Although use of thromboelastography (TEG) to diagnose coagulopathy and guide clinical decision-making is increasing, relative performance of different TEG methods has not been well-defined. Rapid-TEG (rTEG), kaolin-TEG (kTEG), and native-TEG (nTEG) were performed on blood samples from burn patients presenting to a regional center from admission to 21 days. Patients were categorized by burn severity, mortality, and fibrinolytic phenotypes (Shutdown [SD], Physiologic [PHYS], and Hyperfibrinolytic [HF]). Manufacturer ranges and published TEG cutoffs were examined. Concordance correlations (Rc) of TEG parameters (R, α-angle, maximum amplitude [MA], LY30) measured agreement and Cohen's Kappa (κ) determined interclass reliability. Patients (n = 121) were mostly male (n = 84; 69.4%), with median age 40 years, median TBSA burn 13%, and mortality 17% (n = 21). Severe burns (≥40% TBSA) were associated with lower admission α-angle for rTEG (P = .03) and lower MA for rTEG (P = .02) and kTEG (P = .01). MA was lower in patients who died (nTEG, P = .04; kTEG, P = .02; rTEG, P = .003). Admission HF was associated with increased mortality (OR, 10.45; 95% CI, 2.54-43.31, P = .001) on rTEG only. Delayed SD was associated with mortality using rTEG and nTEG (OR 9.46; 95% CI, 1.96-45.73; P = .005 and OR, 6.91; 95% CI, 1.35-35.48; P = .02). Admission TEGs showed poor agreement on R-time (Rc, 0.00-0.56) and α-angle (0.40 to 0.55), and moderate agreement on MA (0.67-0.81) and LY30 (0.72-0.93). Interclass reliability was lowest for R-time (κ, -0.07 to 0.01) and α-angle (-0.06 to 0.17) and highest for MA (0.22-0.51) and LY30 (0.29-0.49). Choice of TEG method may impact clinical decision-making. rTEG appeared most sensitive in parameter-specific associations with injury severity, abnormal fibrinolysis, and mortality.

Evaluation of the use of a heparin dose-response test in dogs to determine the optimal heparin dose during intravascular procedures and assessment of the in vitro heparin response in healthy dogs.

BACKGROUND: No guidelines for administering and monitoring anticoagulants intraprocedurally are currently available in dogs, despite the prevalence of procedures necessitating systemic anticoagulation with heparin. OBJECTIVES: To evaluate an activated clotting time (ACT)-based heparin dose-response (HDR) test to predict the individual required heparin dose in dogs during intravascular procedures, and to investigate both the in vitro heparin - ACT and in vitro heparin - factor anti-Xa activity (anti-Xa) relationships in dogs. METHODS: Blood was collected from eight healthy beagles undergoing a cardiac procedure and utilised to establish baseline ACT and for in vitro evaluation. Subsequently, 100 IU/kg heparin was administered intravenously (IV) and ACT was remeasured (HDR test). The required heparin dose for an ACT target response ≥300 s was calculated for each individual and ACT was remeasured after administration of this dose. For in vitro testing, a serial heparin blood dilution (0-0.5-1-2-4 international unit (IU)/mL) was prepared and ACT and anti-Xa were determined using whole blood and frozen plasma, respectively. RESULTS: The HDR test overestimated the required heparin dose in 3/7 dogs. In vitro, ACT and anti-Xa increased significantly with increasing blood heparin concentration. Heparin - ACT was nonlinear in 4/8 dogs at heparin concentrations >2 IU/mL, whereas heparin - anti-Xa remained linear throughout the tested range. CONCLUSIONS: The HDR test poorly estimated the required heparin dose in dogs. This is most likely attributed to a nonlinear heparin - ACT relationship, as observed in vitro. Anti-Xa is a promising alternative for ACT; however, unavailability as a point-of-care test and lack of in vivo target values restrict its current use.

Use of a New Standardized Unfractionated Heparin Protocol for Left-Sided Ablation Procedures Improves Time in the Therapeutic ACT Range.

OBJECTIVES: This study evaluated whether a novel standardized heparin dosing protocol used during atrial fibrillation catheter ablation resulted in a higher percentage of therapeutic activated clotting time (ACT) values compared to historic nonstandardized procedures. DESIGN: A retrospective cohort study SETTING: This study was conducted at Ochsner Medical Center, the largest tertiary-care teaching hospital in New Orleans, LA PARTICIPANTS: Patients undergoing catheter-based atrial fibrillation ablation INTERVENTIONS: The authors implemented a standardized heparin protocol, and enrolled 202 patients between November 2020 and March 2021. The historic controls consisted of 173 patients who underwent atrial fibrillation ablation between April 2020 and September 2020. Heparin administration in the control group was based on physician preference and was nonstandardized. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was the percentage of intraprocedural ACTs in therapeutic range (≥300 to <450 s). Secondary endpoints included first measured ACT at ≥300 s and percent of measured ACTs in the supratherapeutic range (>450 s). Comparisons were performed using chi-squared tests or Fisher exact tests. Patients in the intervention group had a higher mean percentage of ACTs in the therapeutic range compared to the control group (84.9% vs. 75.8%, p<0.001). More patients in the intervention group reached therapeutic ACT on the first measurement compared to the control group (70.3% vs. 31.2%, p<0.001). CONCLUSION: During catheter-based cardiac ablation procedures, a novel standardized unfractionated heparin dosing protocol resulted in a higher percentage of ACTs in the target range, and a higher proportion of initial ACTs in the therapeutic range compared with baseline nonstandardized heparin dosing.

Activated clotting time and outcomes of chronic total occlusion percutaneous coronary intervention: insights from the PROGRESS-CTO Registry.

BACKGROUND: The optimal range of activated clotting time (ACT) in chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study. METHODS: We examined the association between ACT and in-hospital ischemic and bleeding outcomes in patients who underwent CTO PCI in the Prospective Global Registry for the Study of CTO Intervention. RESULTS: ACT values were available for 4377 patients who underwent CTO PCI between 2012 and 2023 at 29 centers. The mean ACT distribution was less than 250 seconds (19%), 250 to 349 seconds (50%), and greater than or equal to 350 seconds (31%). The incidence of ischemic events, bleeding events, and net adverse cardiovascular events (NACE) was 0.8%, 3.0%, and 3.8%, respectively. In multiple logistic regression analysis, increasing nadir ACT was associated with decreasing ischemic events (adjusted odds ratio [aOR] per 50-second increments: 0.69 [95% confidence interval (CI), 0.50-0.94; P=.017]; and increasing peak ACT was associated with increasing bleeding events (aOR per 50-second increments: 1.17 [95% CI ,1.01-1.36; P=.032]). A U-shaped association was seen between mean ACT and NACE, where restricted cubic spline analysis demonstrated that patients with a low ( less than 200 seconds) or high ( greater than 400 seconds) ACT had increasing NACE risk compared with an ACT of 200 to 400 seconds (aOR 2.06, 95% CI 1.18-3.62; P=.012). CONCLUSIONS: Among patients who underwent CTO PCI, mean ACT had a U-shaped relationship with NACE, where patients with a low ( less than 200 seconds) ACT (driven by ischemic events) or high ( greater than 400 seconds) ACT (driven by bleeding) had higher NACE compared with an ACT of 200 to 400 seconds.

Feasibility and safety values of activated clotting time-guided systemic heparinization in coil embolization for unruptured intracranial aneurysms.

OBJECTIVE: This study aimed to evaluate the feasibility and safety values of activated clotting time (ACT)-guided systemic heparinization in reducing periprocedural thrombosis and bleeding complications during coil embolization of unruptured intracranial aneurysms. METHODS: A total of 228 procedures performed on 213 patients between 2016 and 2021 were included in the retrospective analysis. The target ACT was set at 250 s. Logistic regression was performed to assess predictors for the occurrence of thrombosis and bleeding. Receiver operating characteristic (ROC) analyses were employed to determine the optimal cut-off values for ACT, heparinization, and procedure time. RESULTS: Most (85.1%) of procedures were stent-assisted embolization. The mean baseline ACT was 128.8 ± 45.7 s. The mean ACT at 20 min after the initial intravenous heparin loading of 78.2 ± 18.8 IU/kg was 185 ± 46.4 s. The mean peak ACT was 255.6 ± 63.8 s with 51.3% (117 cases) achieving the target ACT level. Peak ACT was associated with symptomatic thrombosis (OR per second, 1.008; 95% CI, 1.000-1.016; P = 0.035) (cut-off value, 275 s; area under ROC (AUROC), 0.7624). Total administered heparin dose per body weight was negatively associated with symptomatic thrombosis (OR per IU/kg, 0.972; 95% CI, 0.949-0995; P = 0.018) (cut-off value, 294 IU/kg; AUROC, 0.7426) but positively associated with significant bleeding (OR, 1.008 per IU/kg; 95% CI, 1.005-1.012; P <0 .001) (cut-off value, 242 IU/kg; AUROC, 0.7391). Procedure time was significantly associated with symptomatic thrombosis (OR per minute, 1.05; 95% CI, 1.017-1.084; P value = 0.002) (cut-off value, 158 min; area under ROC, 0.8338). CONCLUSION: This study demonstrated that ACT-guided systemic heparinization was feasible to achieve the target ACT value and proposes probable safety thresholds to prevent periprocedural complications through reducing procedure time during coil embolization of unruptured intracranial aneurysms in the stent era.

Variability in Contemporary Heparin Prescription and Activated Clotting Time Monitoring During Percutaneous Coronary Intervention: Call for Up-To-Date Evidence-Based Guidelines.

BACKGROUND: Unfractionated heparin (UFH) is the preferred anticoagulant agent in percutaneous coronary intervention (PCI) procedures for minimising the risk of thrombotic complications. Because of the narrow therapeutic range of UFH, some society guidelines have advocated the use of the activated clotting time (ACT) test to monitor anticoagulation intensity during PCI to reduce thrombotic and bleeding complications. We aimed to assess the current practice of UFH prescription and its monitoring in Australia and New Zealand (ANZ). METHOD: We conducted an anonymous voluntary cross-sectional survey of interventional cardiologists (ICs) who were members of the Cardiac Society of Australia and New Zealand in 2022. The survey included 10 questions pertaining to the current practice of anticoagulation during PCI. RESULTS: Of 430 ICs surveyed, 148 responded (response rate, 34.4%). Most ICs (84.4%) prescribed 70-100 IU/kg of UFH for PCI. Over half of ICs (58.7%) routinely measured ACT during PCI, whereas only 22.2% routinely measured ACT after PCI to guide additional UFH prescription. Among ICs who prescribed additional UFH, approximately half (48%) aimed for ACT ≥250 seconds. Factors that influenced post-PCI UFH prescription included vascular access site and concomitant antiplatelet or anticoagulant therapy. CONCLUSIONS: The contemporary practice of UFH prescription during PCI and ACT monitoring in ANZ is variable and based on outdated evidence preceding current drug-eluting stents, antiplatelet therapies, and radial-first practice. Current society guideline recommendations lack clarity and agreement, reflecting the quality of the available evidence. Up-to-date clinical trials evaluating UFH prescription and ACT monitoring are needed to optimise clinical outcomes in contemporary PCI procedures.

Systemic anticoagulation in ECMO.

While unfractionated heparin (UFH) remains the mainstay of anticoagulation during pediatric extracorporeal life support, direct thrombin inhibitors (DTIs) are increasingly used. In this article, we will review most recent evidence regarding utilization of both UFH and DTIs and compare their known advantages and disadvantages. We will present anticoagulation monitoring strategies during ECMO and outline the most recent Extracorporeal Life Support Organization's anticoagulation guidelines, however with the caveat that there are no true consensus recommendations for anticoagulation management in pediatric ECMO. With these updates, we will serve as the bedside clinician's refresher on common practices for anticoagulation during "routine" ECMO. We will additionally highlight special circumstances, including high risk surgical procedures during ECMO, in which adjustments in anticoagulation and/or addition of antifibrinolytic therapy might mitigate risk.

The Additional Value of Activated Clotting Time-Guided Heparinization During Interventions for Peripheral Arterial Disease.

PURPOSE: Unfractionated heparin is widely used to lower the risk of arterial thromboembolic complications (ATECs) during interventions for peripheral arterial disease (PAD), but it is still unknown which heparin dose is the safest in terms of preventing ATECs and bleeding complications. This study aims to evaluate the incidence of complications during interventions for PAD and the relation between this incidence and different heparinization protocols. MATERIALS AND METHODS: A retrospective analysis of a prospective multicenter cohort study was performed. Between June 2015 and September 2022, 355 patients who underwent peripheral interventions for PAD were included. All patients who were included before July 2018 received 5000 international units (IU) of heparin (group 1). Starting from July 2018, all included patients received an initial dose of 100 IU/kg, with potential additional heparin doses based on activated clotting time (ACT) values (group 2). Data on ACT values and complications within 30 days post-procedurally were collected. RESULTS: In total, 24 ATECs and 48 bleeding complications occurred. In group 1, 8.7% (n=11) of patients suffered from ATEC, compared with 5.7% (n=13) in group 2. Thirteen percent of patients (n=17) in group 1 had a bleeding complication, compared with 14% (n=31) in group 2. Arterial thromboembolic complications were more often found in patients with peak ACT values of <200 seconds, compared with ACT values between 200 and 250 seconds, 15% (n=6) versus 5.9% (n=9), respectively, p=0.048. Patients with peak ACT values >250 seconds had a higher incidence of bleeding complications compared with an ACT between 200 and 250 seconds, 24% (n=21) versus 9.8% (n=15), respectively, p=0.003. Forty-four percent of patients (n=23) in group 1 reached a peak ACT of >200 seconds, compared with 95% (n=218) of patients in group 2 (p=0.001). CONCLUSION: ATEC was found in 6.8% (n=24) and bleeding complications in 14% (n=48) of patients who underwent a procedure for PAD. There was a significantly higher incidence of ATECs in patients with a peak ACT value <200 seconds, and a higher incidence of bleeding complications in patients with a peak ACT value >250 seconds. The findings obtained from this study may serve as a basis for conducting future research on heparinization during procedures for PAD, with a larger sample size. CLINICAL IMPACT: Heparin is administered during arterial interventions for peripheral arterial disease (PAD) to decrease the risk of arterial (thrombo)embolic complications (ATEC) during or shortly following surgery. The effect of heparin is unpredictable in the individual patient, and the optimal dosage of this anticoagulant has not yet been established. Using the activated clotting time (ACT), the anticoagulatory effect of heparin can be monitored periprocedurally. Previous research on the incidence of both ATEC and bleeding complications, or on the optimal dosage of heparin administration, is scarce. This study aims to investigate the incidence of ATEC and bleeding complications between 2 different dosage protocols of heparin-a standard bolus of 5000 IU or ACT-guided heparinization-and thereby provide clarity on the optimal dose of heparin during peripheral arterial interventions for PAD.