Creating a Standardized Process for Testing the Differences in Arterial Versus Venous Activated Coagulation Times

When arterial blood samples for activated clotting time (ACT) are difficult to obtain from the arterial sheath during coronary intervention, venous ACT serves as a substitute. Data are lacking on whether arterial and venous ACT are identical and whether one can serve as an effective substitute for the other. Forty-eight patients undergoing percutaneous transluminal coronary angioplasty (PTCA) were prospectively evaluated to answer this question. Simultaneous arterial and venous ACT samples were drawn from femoral artery and vein vascular sheaths before and during each procedure, and ACT values were determined with a Hemochron automated electronic timer. Porcine heparin dosing was guided by arterial ACT in the first 25 patients and by venous ACT in the last 23 patients. The target ACT value used for continued heparin dosing was 400 sec. At baseline and throughout the study up to 60 min, venous ACT was slightly and significantly greater than arterial ACT. Despite this statistical difference in ACT values, there was no difference in complication rate between the two groups, and the amount of heparin used during either guiding regimen was the same. Therefore, although venous ACT values are slightly higher than arterial, the more convenient venous ACT can be safely used to guide heparin dosing during PTCA when using a target ACT value of 400 sec.

When arterial blood samples for activated clotting time (ACT) are difficult to obtain from the arterial sheath during coronary intervention, venous ACT serves as a substitute. Data are lacking on whether arterial and venous ACT are identical and whether one can serve as an effective substitute for the other. Forty-eight patients undergoing percutaneous transluminal coronary angioplasty (PTCA) were prospectively evaluated to answer this question. Simultaneous arterial and venous ACT samples were drawn from femoral artery and vein vascular sheaths before and during each procedure, and ACT values were determined with a Hemochron automated electronic timer. Porcine heparin dosing was guided by arterial ACT in the first 25 patients and by venous ACT in the last 23 patients. The target ACT value used for continued heparin dosing was 400 sec. At baseline and throughout the study up to 60 min, venous ACT was slightly and significantly greater than arterial ACT. Despite this statistical difference in ACT values, there was no difference in complication rate between the two groups, and the amount of heparin used during either guiding regimen was the same. Therefore, although venous ACT values are slightly higher than arterial, the more convenient venous ACT can be safely used to guide heparin dosing during PTCA when using a target ACT value of 400 sec. © 1996 Wiley-Liss, Inc.

Background: Activated Clotting Time (ACT) guided heparinization is the gold standard for titrating unfractionated heparin (UFH) administration during atrial fibrillation (AF) ablation procedures. The current ACT target (300 s) is based on studies in patients receiving a vitamin K antagonist (VKA). Several studies have shown that in patients receiving Direct Oral Anticoagulants (DOACs), the correlation between ACT values and UFH delivered dose is weak. Objective: To assess the relationship between ACT and real heparin anticoagulant effect measured by anti-Xa activity in patients receiving different anticoagulant treatments. Methods: Patients referred for AF catheter ablation in our centre were prospectively included depending on their anticoagulant type. Results: 113 patients were included, receiving rivaroxaban (n = 30), apixaban (n = 30), dabigatran (n = 30), and VKA (n = 23). To meet target ACT, a higher UFH dose was required in DOAC than VKA patients (14,077.8 IU vs. 9565.2 IU, p < 0.001), leading to a longer time to achieve target ACT (46.5 min vs. 27.3 min, p = 0.001). The correlation of ACT and anti-Xa activity was tighter in the VKA group (Spearman correlation ρ = 0.53), compared to the DOAC group (ρ = 0.19). Despite lower ACT values in the DOAC group, this group demonstrated a higher mean anti-Xa activity compared to the VKA group (1.56 ± 0.39 vs. 1.14 ± 0.36; p = 0.002). Conclusion: Use of a conventional ACT threshold at 300 s during AF ablation procedures leads to a significant increase in UFH administration in patients treated with DOACs. This increase corresponds more likely to an overdosing than a real increase in UFH requirement.

Uninterrupted use of oral anticoagulants before atrial fibrillation (AF) ablation can reduce the incidence of perioperative thromboembolic events. However, the effect of new oral anticoagulants on activated clotting time (ACT) in response to heparin during AF ablation in Chinese populations remains unknown. The aim of the present retrospective study was to investigate the value of ACTs in response to intraoperative heparin administration in patients using dabigatran or rivaroxaban. From January 2018 to December 2021, a total of 173 patients undergoing AF ablation were included in the study, in which 101 patients were treated with dabigatran, 72 patients were treated with rivaroxaban. The intraoperative ACT values were examined in both groups. The incidence of periprocedural complications was evaluated. Initial heparin dosage (88 ± 19 U/kg vs. 78 ± 27 U/kg, P < 0.05), total heparin dosage (137 ± 41 U/kg vs. 106 ± 52 U/kg, P < 0.05) during the ablation procedure were higher in the dabigatran group than those in the rivaroxaban group. Mean ACT (280 ± 36 s vs. 265 ± 30 s, P < 0.05), and the percentage of ACTs within the therapeutic range (250-350 s) (74% ± 26% vs. 60% ± 29%, P < 0.05) were significantly lower in the dabigatran group than those in the rivaroxaban group, particularly in male patients. Furthermore, the average time of achieving the target ACT (250-350 s) was also found longer in the dabigatran group (P < 0.05) as compared with the rivaroxaban group. No significant difference was found in the incidence of periprocedural complications between the two groups. The anticoagulant effect of uninterrupted rivaroxaban therapy appears to be more stable and efficient than dabigatran administration during catheter ablation in patients with AF.

Objective: Differences in the activated coagulation time (ACT) during ablation and adequate heparin dosing were observed among atrial fibrillation (AF) patients undergoing AF catheter ablation receiving different anticoagulation therapies and the suitable heparin dosing during ablation among patients treated with different anticoagulation therapies was explored. Methods: Patients who received warfarin (n=100), low-molecular-weight heparin (n=100), dabigatran etexilate (n=98, 110 mg, Bid) and rivaroxaban (n=48, 20 mg, Qd) were included. All of them underwent the first AF ablation during January 2016 to December 2017 and patients with hepatic and renal dysfunction were excluded. Initial bolus heparin (100 U/kg, intravenous) was applied to all patients. Additional heparin dosage was added according to the ACT, which was measured in 15-minute interval to maintain the ACT within 250-350 seconds until the end of ablation. Patient characteristics, ACT and complications were compared among various groups. Results: The baseline general characteristics among patients were similar. The baseline ACTs in the dabigatran groups were significantly longer than those in the rivaroxaban group ((133±36) seconds vs. (113±22) seconds, P<0.05). The 15 min ACT in the warfarin group was longer than in the dabigatran group ((259±56) seconds vs. (243±43) seconds, P<0.05). The 15-minute ACTs were significantly longer in the warfarin ((259±56) seconds) and dabigatran ((243±43) seconds) groups compare with low-molecular-weight heparin group ((224±40) seconds) and rivaroxaban group ((226±32) seconds) (all P<0.05). The same trend was also observed in the rate of reaching ACT goal after initial-standard-dosage of heparin (warfarin (53%, 53/100), dabigatran (45%,44/98), low-molecular-weight heparin (28%,28/100), rivaroxaban (23%,11/48), P<0.05). The 1 hour ACT in the warfarin group ((254±49) seconds) was significantly longer than the other three groups (dabigatran (233±33) seconds, low-molecular-weight heparin (226±34) seconds, rivaroxaban (231±30) seconds, all P<0.01). The rate of reaching ACT goal at 1 hour were significantly higher in the warfarin group (66%,35/53) than in the dabigatran group (41%,18/44), and rivaroxaban group (27%,3/11) (all P<0.05). The total heparin required was significantly higher in rivaroxaban group than in the dabigatran and warfarin groups (all P<0.05). During the perioperative period, no patient exhibited any thromboembolic complications, and only a few minor bleeding complications was observed among patients, which was similar between the four groups (P>0.05). Conclusion: Higher dosage of heparin is required during AF ablation to achieve the satisfactory anticoagulant intensity for AF patients under dabigatran etexilate (110 mg, Bid), low-molecular-weight heparin and rivaroxaban (20 mg, Qd) anticoagulation therapy before AF ablation.

Impact of dabigatran, rivaroxaban, apixaban and edoxaban on activated clotting time: an in vitro study

The correct monitoring of heparin therapy and its reversal determines the successful conduct of cardiovascular surgery with extracorporeal circulation (ECC). The activated coagulation time (ACT) and the heparin management test (HMT) are the most frequently used tests in the operating room. Three compact monitors for ACT or HMT are here evaluated. Forty samples were obtained, at 10-min intervals, from eight patients during ECC. The ACT or HMT was immediately performed using: Hemochron juniors ACT, CoaguCeck Pro (ACT) and Rapid Point Coag (HMT). Data were compared between them and with the heparin levels, measured as anti-Xa. The simple least squares linear regression among, respectively, Hemochron Junior ACT, CoaguCeck Pro ACT, Rapid Point Coag HMT and anti-Xa activity were i=452.3, s=15.2, Sy/x=37.5, r=0.18; i=411.9, s=22.1, Sy/x=48.7, r=0.21 and i=479.4, s=9.0, Sy/x=9.3; r=0.41. CoaguCeck Pro ACT results were above the upper detection limit (500 s) in 37 of 40 determinations. The comparison between ACT Hemocron and HMT Rapid Point Coag shows i=35.7, s=0.9, Sy/x=35.4, r=0.68, with a bias of 29.0 s (CI: 17.9-40.1), 95% of agreement between -41.5 s (CI: -60.7 to -22.3) and 99.5 s (CI: 80.4-118.7). Taking a concentration of 2.0 U/ml of heparin to discriminate between high- and low-risk conditions, receiver-operator characteristic (ROC) curve was used to rank the performance of the methods. Areas under the ROC curve+/-SE for Hemochron Junior ACT and Rapid Point Coag HMT were 0.629+/-0.097 and 0.543+/-0.096. The results obtained by HMT appear similar to those obtained by the ACT for monitoring high-dose heparin therapy in patients undergoing ECC. HMT appeared to perform better than ACT in measuring the heparin effect, while the ROC analysis gives a little more accuracy for ACT. Neither of the two methods is able to achieve enough evidence of diagnostic accuracy. Since these tests are widely used, and there are no laboratory alternatives, a real comparison with the outcome of the patients should be helpful for an evidence-based evaluation of these point-of-care tests.

Effect of abciximab versus tirofiban on activated clotting time during percutaneous intervention and its relation to clinical outcomes—observations from the TARGET trial

Although warfarin has traditionally been used for reducing risk of stroke in patients with atrial fibrillation, over the past year, the direct thrombin inhibitor dabigatran has become an accepted alternative. No study has conclusively investigated bleeding risks of patients treated with dabigatran immediately following radiofrequency catheter ablation (RFCA) procedures. We evaluated 156 consecutive patients referred for RFCA of atrial arrhythmias: 31 patients were on dabigatran and 125 patients were on warfarin. The incidence of bleeding complications during the first 48 h and the first week following ablation were recorded and comparisons made using Fisher's exact test. Major complications were defined as hemorrhage requiring blood products or the need for vascular intervention. Minor complications were defined as prolonged bleeding from the catheter insertion site, hematoma formation, or development of ecchymosis. Our study also took into account the intraprocedure activated clotting time (ACT) levels in an effort to describe any differences between both patient groups. There were no differences in age, gender, procedure type, or level of intraprocedural anticoagulation between the warfarin and dabigatran groups. No major bleeding complications were observed in either patient group at either 48 h or 1 week postprocedure. Six of the 31 dabigatran patients and 21 of the 125 warfarin patients had minor bleeding complications. There was no statistically significant difference between the incidence of minor bleeding complications between the two groups (p = 0.7384), although rebleeding was more commonly observed in patients on dabigatran. In regard to the intraprocedure ACT levels, there was more variability in the dabigatran patient group, and it was more difficult to achieve the goal ACT level, yet these results did not affect overall bleeding complications. In our cohort, bleeding-related complications 48 h and 1 week post-ablation were similar for warfarin and dabigatran. Dabigatran is associated with more intraprocedural variability in ACT than warfarin.

For selected patients with atrial fibrillation (AF), catheter ablation is an important treatment alternative and has about a 70 % success rate in carefully selected patients. Patients undergoing this procedure are at an increased risk of thromboembolic events during and following the ablation procedure. Bridging of anticoagulation, insertion of sheaths and catheters, left atrial endothelial damage, and atrial stunning may all lead to this increased thromboembolic risk. In order to minimize these thromboembolic events, anticoagulation, initiated as part of the procedure, increases bleeding complications including pericardial tamponade and vascular complications. Controlled data are not available to guide anticoagulation management of such patients during the peri-ablation period. Several years ago, we used to discontinue warfarin for several days before the procedure and the anticoagulation bridged with subcutaneous low molecular weight heparin (LMWH). The main limitation of this approach is that patients require LMWH after the procedure until the international normalized ratio (INR) becomes therapeutic. Excessive anticoagulation with LMWH and periods of subtherapeutic INR on warfarin post-procedure, have resulted in bleeding and thrombo-embolic complications [1]. More recently, in order to reduce these limitations, it has become more common to perform the ablation procedure without discontinuation of warfarin [2–4]. Several studies have demonstrated that uninterrupted warfarin is associated with fewer bleeding complications compared to LMWH bridging. With both approaches, unfractionated heparin is administered during the procedure and the dosing regimen is guided by a target activated clotting time (ACT) ranging from 225 to 450. Heparin infusion is discontinued once all catheters have been removed and the sheaths are removed once the ACT is less than 200 s. Post-procedure LMWH is usually not required since the patient is on a therapeutic level of anticoagulation with warfarin. Anticoagulation is then continued for 3–6 months or indefinitely depending on the patient’s risk factors. The problem with the above protocols is that there is no gold standard based on carefully collected prospective controlled data and the FDA has never approved LMWH bridging as an indication for this type of perioperative use. The commercial approval of dabigatran and rivaroxaban (and soon apixaban and edoxaban) has created a new anticoagulation challenge for AF patients undergoing catheter ablation procedures. Dabigatran has been commercially available for about 2 years and several reports have been published related to the safety and efficacy of using this drug during AF ablation procedures. Winkle et al. [5] demonstrated dabigatran to be safe and well tolerated when used after AF ablation (interrupted use prior to the ablation procedure) in a single-center study. The study included patients previously treated with warfarin, dabigatran, or aspirin. The post-procedure use of dabigatran was not associated with any major bleeding or thromboembolic events. However, three patients had to stop dabigatran due to dyspepsia, rash, and diarrhea. In this study, dabigatran was discontinued 36– 60 h prior to the procedure based on renal function and restarted 22 h after the procedure (post-procedure LMW heparin was given). The target ACT during the procedure was 225 s. A larger multicenter study by Lakkireddy et al. [6] reported that periprocedural dabigatran use significantly G. V. Naccarelli (*) :M. D. Gonzalez Electrophysiology Program, Heart and Vascular Institute, Penn State University College of Medicine, 500 University Drive, Room H1511, P. O. Box 850, MC H047, Hershey, PA 17033, USA e-mail: gnaccarelli@hmc.psu.edu

Intrinsic pathway–dependent activated clotting time is not reliable for monitoring anticoagulation during cardiopulmonary bypass in neonates

The use of direct factor Xa inhibitors rivaroxaban and apixaban (XABANs) has rapidly increased; however, there is no validated test available to monitor the effect on hemostasis. This study aims to assess how hemostatic management based on the Rapid Thromboelastography (R-TEG) variable activated clotting time (ACT) of XABAN patients with ongoing bleedings or in need for acute surgical intervention, affected patient outcome. A total of 343 XABAN patients were included in the main analysis together with 50 healthy volunteers to validate the reference value for ACT. An ACT >120 s (s) was defined as having XABAN-induced coagulopathy. Sixty-five percent of the XABAN patients presented with R-TEG ACT within the normal reference. Patients with XABAN-induced coagulopathy had a significantly increased risk of severe bleeding. Significantly more patients with extra-cerebral bleeding (ECB) and ACT above 120 s were transfused with five red blood cell (RBC) units or more compared to patients with ACT at 120 s or below (17% vs. 3%, p <.05). Significantly more XABAN-patients with ACT above 120 s received pro-hemostatic intervention with prothrombin complex concentrate (PCC) when compared to those with ACT at 120 s or below (ECB: 2% vs. 8%, p =.03, intracranial hemorrhage: 25% vs. 68%, p <.00). Patients who received PCC had a higher 30- and 90-day mortality compared to the rest of the cohort (16% vs. 6%, p = .02 and 21% vs. 7%, p =.00). Patients with XABAN-induced coagulopathy as evaluated by R-TEG ACT presented with more severe bleeding and higher transfusion requirements when compared to those with ACT in the normal range. This suggests that R-TEG ACT measurement in XABAN patients with active hemorrhage or in need for acute surgery may be of clinical value.

Response

The Thrombelastograph (TEG; Haemoscope Corp., Skokie, IL) coagulation analyzer is an effective point-of-care monitor for routine clinical practice and clinical research. Prior investigators have used either arterial or venous samples of blood for TEG measurements. We conducted this prospective cohort study to determine potential differences in TEG variables between arterial and venous blood samples. Arterial and venous samples were drawn from 40 cardiac surgical patients, yielding 134 pairs for comparison. Twenty-nine comparisons (control) were between arterial and arterial samples and were not significantly different. For the arterial and venous comparisons (n = 105), mean (+/-sd) arterial and venous values were the following: reaction time, 10 +/- 2 mm vs 13 +/- 4 mm, P = 0.004; maximum amplitude, 59 +/- 9 mm vs 49 +/- 12 mm, P < 0.001; alpha angle, 61 +/- 10 degrees vs 51 +/- 14 degrees, P < 0.001; K, 5 +/- 2 mm vs 8 +/- 4 mm, P = 0.007; and lysis, 2.5 +/- 1.7 vs 2.5 +/- 2.0 (not significant), arterial versus venous, respectively. Arterial blood samples demonstrated TEG values reflecting stronger (larger maximum amplitude) and faster (shorter reaction time and K value, wider alpha angle) clot formation. The results suggest that users of TEG coagulation analyzers should be consistent with the site of blood sampling given the potential differences obtained. Thrombelastograph (TEG) values obtained from venous blood samples differ from values obtained from arterial blood samples. When the TEG coagulation analyzer is used for clinical purposes, it is important to be consistent in the blood collection site.

Two cases of fatal thrombosis after aminocaproic acid therapy and deep hypothermic circulatory arrest.