Hemostatic Activation and Inflammatory Response during Cardiopulmonary Bypass

2002 ◽  
Vol 97 (4) ◽  
pp. 837-841 ◽  
Author(s):  
Andreas Koster ◽  
Thomas Fischer ◽  
Michael Praus ◽  
Helmut Haberzettl ◽  
Wolfgang M. Kuebler ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Cardiopulmonary Bypass ◽  
Inflammatory Response ◽  
Thrombin Generation ◽  
Antithrombin Iii ◽  
Clotting Time ◽  
Anticoagulation Management ◽  
Heparin Concentration ◽  
Activated Clotting Time ◽  
Inflammatory System

Background Cardiac surgery involving cardiopulmonary bypass (CPB) leads to fulminant activation of the hemostatic-inflammatory system. The authors hypothesized that heparin concentration-based anticoagulation management compared with activated clotting time-based heparin management during CPB leads to more effective attenuation of hemostatic activation and inflammatory response. In a randomized prospective study, the authors compared the influence of anticoagulation with a heparin concentration-based system (Hepcon HMS; Medtronic, Minneapolis, MN) to that of activated clotting time-based management on the activation of the hemostatic-inflammatory system during CPB. Methods Two hundred elective patients (100 in each group) undergoing standard cardiac surgery in normothermia were enrolled. No antifibrinolytic agents or aprotinin and no heparin-coated CPB systems were used. Samples were collected after administration of the heparin bolus before initiation of CPB and after conclusion of CPB before protamine infusion. Results There were no differences in the pre-CPB values between both groups. After CPB there were significantly higher concentrations ( < 0.05) for heparin and a significant reduction in thrombin generation (25.2 +/- 21.0 SD vs. 34.6 +/- 25.1), d-dimers (1.94 +/- 1.74 SD vs. 2.58 +/- 2.1 SD), and neutrophil elastase (715.5 +/- 412 SD vs. 856.8 +/- 428 SD), and a trend toward lower beta-thromboglobulin, C5b-9, and soluble P-selectin in the Hepcon HMS group. There were no differences in the post-CPB values for platelet count, adenosine diphosphate-stimulated platelet aggregation, antithrombin III, soluble fibrin, Factor XIIa, or postoperative blood loss. Conclusion Compared with heparin management with the activated clotting time, heparin concentration-based anticoagulation management during CPB leads to a significant reduction of thrombin generation, fibrinolysis, and neutrophil activation, whereas there is no difference in the effect on platelet activation. The generation of fibrin even in the presence of high heparin concentrations most likely has to be attributed to the reduced antithrombin III concentrations or reduced inhibition of clot-bound thrombin. Therefore, in addition to maintenance of higher heparin concentrations, monitoring and substitution of antithrombin III should be considered to ensure more efficient antithrombin activity during CPB.

Factors associated with errors in the heparin dose response test: recommendations to improve individualized heparin management in cardiopulmonary bypass

Perfusion ◽  
2020 ◽  
pp. 026765912095297
Author(s):  
Min-Ho Lee ◽  
William Riley
Keyword(s):  
Cardiopulmonary Bypass ◽  
Dose Response ◽  
Clotting Time ◽  
Critical Aspect ◽  
Heparin Dose ◽  
Factors Associated ◽  
Heparin Concentration ◽  
Activated Clotting Time

Background: A critical aspect of cardiopulmonary bypass (CPB) is to achieve full anticoagulation to prevent thrombosis and consumptive coagulation without using excessive amount of heparin. This can be achieved with heparin dose response (HDR) test in vitro to calculate an individualized heparin bolus to reach a target activated clotting time (ACT) and heparin concentration. However, we often observe that the measured ACT (mACT) with the calculated heparin bolus gives significant errors, both positive (mACT is higher than expected) and negative (mACT is lower), from expected ACT (eACT). Methods: We performed a retrospective study of 250 patients who underwent cardiac surgery to attain an error distribution of the mACT from eACT with calculated heparin bolus. In addition, it is aimed to identify possible patterns of baseline ACT (bACT), calculated heparin concentration (CHC) and HDR slope that are associated with the significant positive and negative errors. Results: We found that individualized heparin bolus by HDR test is consistently underestimated while it gave a significant number of positive and negative errors. Further analysis indicates that significant negative errors correlate with high bACT and slope and low CHC while significant positive errors with low bACT and slope and high CHC. Conclusion: The mACT can be substantially different from eACT. The accuracy of the HDR test appears to be dependent upon bACT, slope, and CHC. Based on our analysis, we provide several recommendations and a flow chart to improve the quality of individualized heparin management on CPB.

scholarly journals Anticoagulation in Cardiopulmonary Bypass

1977 ◽  
Author(s):  
C. Thomas Kisker ◽  
John A. Young ◽  
Donald B. Doty ◽  
Barbara J. Taylor
Keyword(s):  
Cardiopulmonary Bypass ◽  
Antithrombin Iii ◽  
Human Subjects ◽  
Mean Value ◽  
Clotting Time ◽  
Excessive Bleeding ◽  
Safe Level ◽  
Activated Clotting Time ◽  
Before And After ◽  
The Mean

Prolonging the activated clotting time (ACT) 2 to 3 times normal is said to provide a “safe” level of anticoagulation during cardiopulmonary bypass. To test this level of anticoagulation 9 monkeys were anticoagulated with heparin at the start of cardiopulmonary bypass so that ACT’s ranged from 201 sec to > 1000 sec (normal 91 sec). ACT, platelet count (P), fibrinogen (F), and fibrin monomer (FM) were measured at 10, 30, 60, 90, and 120 minutes during bypass. Antithrombin III (AT3) was measured before and after bypass. Six monkeys developed increased FM indicating active coagulation beginning from 10 to 60 minutes on bypass. ACT’s were > 200 sec in all animals at the time of FM detection. P fell below 100,000/mm3 in the 6 animals with elevated FM, but remained above 100,000/mm3 in the other 3 animals. The mean value of AT3 (69%) decreased to 24.4% after bypass in the 6 animals with elevated FM, but was 61% after bypass in the others. Scanning electron microscopy of the oxygenator membranes showed significant amounts of fibrin on the membranes used in monkeys who developed increased FM levels, but not on those with normal FM concentrations. F decreased from 167 mgm/dl to 80.5 mgm/dl in monkeys with elevated FM and to 117 mgm/dl in those with normal FM concentrations. Excessive bleeding did not occur in the animals without increased FM although ACT’s were in excess of 1000 sec. Subsequently three human subjects on cardiopulmonary bypass whose ACT’s were maintained above 400 sec have not shown increased FM levels. The results suggest that prolonging the ACT more than 2 - 3 times normal is required to prevent activation of clotting during cardiopulmonary bypass.

A comparative analysis of four activated clotting time measurement devices in cardiac surgery with cardiopulmonary bypass

Perfusion ◽  
2020 ◽  
pp. 026765912094935
Author(s):  
Han Li ◽  
Cyril Serrick ◽  
Vivek Rao ◽  
Paul M Yip
Keyword(s):  
Cardiac Surgery ◽  
Cardiopulmonary Bypass ◽  
System Analysis ◽  
Point Of Care ◽  
Measurement Range ◽  
Medical Decision ◽  
Clotting Time ◽  
Activated Clotting Time ◽  
Decision Points ◽  
Heparin Anticoagulation

Background: In cardiac surgery on cardiopulmonary bypass (CPB), heparin anticoagulation is monitored by point-of-care measurement of activated clotting time (ACT). The objective of this study was to compare four ACT systems in cardiac surgery in terms of their reproducibility, agreement and potential clinical impact at relevant medical decision points. Methods: The study included 40 cardiac surgery patients. Samples were taken at five time points before (T1), after heparinization for CPB (T2, T3, T4), and after heparin reversal (T5). The reproducibility, correlation, and differences in ACT values were assessed with two devices from each of the four ACT systems: Instrumentation Laboratory Hemochron Elite (Hmch), Medtronic HMS Plus (HMS), Abbott i-STAT, and Helena Abrazo. Subrange analyses were performed for low ACT values (results from T1, T5) and high ACT values (results from T2, T3, T4). Results: Within-system analysis showed strong linear correlation between paired measurements (R = 0.968-0.993). However, Hmch showed poorer reproducibility with highest proportion of values that exceed a difference of 10% and highest overall standard error of 74 seconds across the measurement range compared to that of the others (range 39-47 seconds, respectively). For inter-system comparison, using Hmch as reference, ACTs were strongly correlated as follows: HMS (R = 0.938), i-STAT (R = 0.911), and Abrazo (R = 0.911). Agreement analysis in the high ACT range showed HMS tended to have higher ACT values with +11% bias over Hmch, whereas i-STAT (–8% bias) and Abrazo (–13% bias) tended to underestimate. Post-protamine ACT results were dependent on device type where Hmch yielded highest post-protamine ACT (+13% higher than baseline) compared to –16% for HMS, –10% for iSTAT and 0% for Abrazo. Conclusions: Each device had individual reproducibility and biases, which may impact peri-operative heparin management. Careful validation must be undertaken when adopting a different method as decision limits would be affected. Clinicians should also be cautious using ACT as the only indicator for full heparin reversal.

Application of goal-directed therapy for the use of concentrated antithrombin for heparin resistance during cardiac surgery

Perfusion ◽  
2020 ◽  
pp. 026765912092608
Author(s):  
Alfred H Stammers ◽  
Stephen G Francis ◽  
Randi Miller ◽  
Anthony Nostro ◽  
Eric A Tesdahl ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Cardiopulmonary Bypass ◽  
Heparin Therapy ◽  
Sensitivity Index ◽  
Transfusion Rate ◽  
Clotting Time ◽  
Activated Clotting Time ◽  
Institutional Review ◽  
Number Of Factors ◽  
Heparin Resistance

The maintenance of anticoagulation in adult patients undergoing cardiopulmonary bypass is dependent upon a number of factors, including heparin concentration and adequate antithrombin activity. Inadequate anticoagulation increases the risk of thrombosis and jeopardizes both vascular and extracorporeal circuit integrity. The purpose of this study was to evaluate a goal-directed approach for the use of antithrombin in patients who were resistant to heparin. Following institutional review board approval, data were obtained from quality improvement records. A goal-directed protocol for antithrombin was established based upon heparin dosing (400 IU kg−1 body weight) and achieving an activated clotting time of ⩾500 seconds prior to cardiopulmonary bypass. Two groups of patients were identified as those receiving antithrombin and those not receiving antithrombin. Outcome measures included activated clotting time values and transfusion rates. Consecutive patients (n = 140) were included in the study with 10 (7.1%) in the antithrombin group. The average antithrombin dose was 1,029.0 ± 164.5 IU and all patients had restoration to the activated clotting time levels. Patients in the antithrombin group were on preoperative heparin therapy (80.0% vs. 24.6%, p = 0.001). Prior to cardiopulmonary bypass the activated clotting time values were lower in the antithrombin group (417.7 ± 56.1 seconds vs. 581.1 ± 169.8 seconds, p = 0.003). Antithrombin patients had a lower heparin sensitivity index (0.55 ± 0.17 vs. 1.05 ± 0.44 seconds heparin−1 IU kg−1, p = 0.001), received more total heparin (961.3 ± 158.5 IU kg−1 vs. 677.5 ± 199.0 IU kg−1, p = 0.001), more cardiopulmonary bypass heparin (22,500 ± 10,300 IU vs. 12,100 ± 13,200 IU, p = 0.016), and more protamine (5.4 ± 1.2 vs. 4.1 ± 1.1 mg kg−1, p = 0.003). The intraoperative transfusion rate was higher in the antithrombin group (70.0% vs. 35.4%, p = 0.035), but no differences were seen postoperatively. Utilization of a goal-directed algorithm for the administration of antithrombin for the treatment of heparin resistance is effective in patients undergoing cardiac surgery.

scholarly journals Comparison of activated clotting times measured using the Hemochron Jr. Signature and Medtronic ACT Plus during cardiopulmonary bypass with acute normovolemic haemodilution

2017 ◽  
Vol 46 (2) ◽  
pp. 873-882 ◽  
Author(s):  
Jung Min Lee ◽  
Eun Young Park ◽  
Kyung Mi Kim ◽  
Jong Chan Won ◽  
Tack Koon Jung ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Cardiac Surgery ◽  
Cardiopulmonary Bypass ◽  
Bolus Dose ◽  
Blood Glucose Concentration ◽  
Altman Analysis ◽  
Clotting Time ◽  
Bland Altman Analysis ◽  
Activated Clotting Time ◽  
Protamine Administration

Objective This study compared the activated clotting time (ACT) measured using the Hemochron Jr. Signature (HACT) with the ACT measured using the Medtronic ACT Plus (MACT) during cardiopulmonary bypass (CPB) with acute normovolemic haemodilution (ANH) in patients undergoing cardiac surgery. Methods The ACT was checked at baseline with both devices after inducing anaesthesia, and 400 to 800 mL of whole blood was withdrawn to induce moderate ANH. Before initiating CPB, a 300-IU/kg bolus dose of heparin was administered to maintain the HACT at >400 s; protamine was later given to reverse the anticoagulation. The ACT was checked using both devices at baseline, during heparinisation, and after protamine administration. Results In total, 106 pairs of samples from 29 patients were analysed. The ACT showed a good correlation between the two devices (r = 0.956). However, Bland–Altman analysis showed that the MACT was higher, particularly at baseline and during heparinisation. Multiple regression analysis showed that the blood glucose concentration significantly influenced the differences between the two ACT devices. Conclusions The HACT was lower than the MACT during CPB with ANH in patients undergoing cardiac surgery. Clinicians should be cautious when using each ACT device within generally accepted reference ACT values.

Anticoagulation management during pulmonary endarterectomy with cardiopulmonary bypass and deep hypothermic circulatory arrest

Perfusion ◽  
2020 ◽  
Vol 36 (1) ◽  
pp. 87-96
Author(s):  
Dennis Veerhoek ◽  
Laurentius JM van Barneveld ◽  
Renard G Haumann ◽  
Suzanne K Kamminga ◽  
Alexander BA Vonk ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Confidence Interval ◽  
Circulatory Arrest ◽  
Deep Hypothermic Circulatory Arrest ◽  
Hypothermic Circulatory Arrest ◽  
Clotting Time ◽  
Pulmonary Endarterectomy ◽  
Anticoagulation Management ◽  
Activated Clotting Time ◽  
Protamine Administration

Introduction: Pulmonary endarterectomy requires cardiopulmonary bypass and deep hypothermic circulatory arrest, which may prolong the activated clotting time. We investigated whether activated clotting time–guided anticoagulation under these circumstances suppresses hemostatic activation. Methods: Individual heparin sensitivity was determined by the heparin dose–response test, and anticoagulation was monitored by the activated clotting time and heparin concentration. Perioperative hemostasis was evaluated by thromboelastometry, platelet aggregation, and several plasma coagulation markers. Results: Eighteen patients were included in this study. During cooling, tube-based activated clotting time increased from 719 (95% confidence interval = 566-872 seconds) to 1,273 (95% confidence interval = 1,136-1,410 seconds; p < 0.01) and the cartridge-based activated clotting time increased from 693 (95% confidence interval = 590-796 seconds) to 883 (95% confidence interval = 806-960 seconds; p < 0.01), while thrombin–antithrombin showed an eightfold increase. The heparin concentration showed a slightly declining trend during cardiopulmonary bypass. After protamine administration (protamine-to-heparin bolus ratio of 0.82 (0.71-0.90)), more than half of the patients showed an intrinsically activated coagulation test and intrinsically activated coagulation test without heparin effect clotting time >240 seconds. Platelet aggregation through activation of the P2Y12 (adenosine diphosphate test) and thrombin receptor (thrombin receptor activating peptide-6 test) decreased (both −33%) and PF4 levels almost doubled (from 48 (95% confidence interval = 42-53 ng/mL) to 77 (95% confidence interval = 71-82 ng/mL); p < 0.01) between weaning from cardiopulmonary bypass and 3 minutes after protamine administration. Conclusion: This study shows a wide variation in individual heparin sensitivity in patients undergoing pulmonary endarterectomy with deep hypothermic circulatory arrest. Although activated clotting time–guided anticoagulation management may underestimate the level of anticoagulation and consequently result in a less profound inhibition of hemostatic activation, this study lacked power to detect adverse outcomes.

Effect of antithrombin in fresh frozen plasma on hemostasis after cardiopulmonary bypass surgery

Perfusion ◽  
2020 ◽  
pp. 026765912094843
Author(s):  
Kazuhiro Shirozu ◽  
Yuji Karashima ◽  
Ken Yamaura
Keyword(s):  
Cardiopulmonary Bypass ◽  
Fresh Frozen Plasma ◽  
Clotting Time ◽  
Rotational Thromboelastometry ◽  
Heparin Concentration ◽  
Antithrombin Activity ◽  
Activated Clotting Time ◽  
Fresh Frozen ◽  
Frozen Plasma ◽  
Maximum Clot Firmness

Introduction: Supplementation of fresh frozen plasma immediately after cardiopulmonary bypass is an effective method to enhance clotting ability as coagulation factors are consumed in the extracorporeal circuit during cardiopulmonary bypass. On the other hand, the anticoagulation factors in fresh frozen plasma can also deter the clotting ability. This study investigated the effect of fresh frozen plasma administration on the comprehensive clotting ability following cardiopulmonary bypass. Methods: This prospective observational study included 22 patients scheduled for cardiac surgery. Clotting times and maximum clot firmness were evaluated using the types of rotational thromboelastometry, intrinsic rotational thromboelastometry, and heparinase thromboelastography preoperatively, immediately after cardiopulmonary bypass, and 1 hour after cardiopulmonary bypass. Activated clotting time, antithrombin activity, and heparin concentration were also measured at these time-points. Results: Antithrombin activity (62.9 ± 7.2% vs. 51.1 ± 7.4%, p < 0.0001) and activated clotting time (132.6 ± 9.6% vs. 120.0 ± 9.0%, p < 0.001) were significantly higher 1 hour after cardiopulmonary bypass compared to measurements taken immediately after cardiopulmonary bypass. Heparin concentration 1 hour after cardiopulmonary bypass was significantly decreased compared to that immediately after cardiopulmonary bypass. On the other hand, maximum clot firmness determined via intrinsic rotational thromboelastometry was significantly greater 1 hour after cardiopulmonary bypass (53.8 ± 4.8 mm) than that immediately after cardiopulmonary bypass (49.5 ± 4.8 mm). Clotting time determined via intrinsic rotational thromboelastometry and heparinase thromboelastography was also significantly shorter 1 hour after cardiopulmonary bypass than that immediately after cardiopulmonary bypass. Conclusion: Fresh frozen plasma administration increased antithrombin activity and caused activated clotting time prolongation, but then increased clotting ability. Thus, testing by rotational thromboelastometry after cardiopulmonary bypass could be valuable in the detection of comprehensive clotting ability.

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