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.

Relationships between antithrombin activity, anticoagulant efficacy of heparin therapy and perioperative variables in patients undergoing cardiac surgery requiring cardiopulmonary bypass

Perfusion ◽  
2011 ◽  
Vol 26 (6) ◽  
pp. 487-495 ◽  
Author(s):  
V Muedra ◽  
S Bonanad ◽  
M Gómez ◽  
V Villalonga ◽  
F Sánchez ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Cardiopulmonary Bypass ◽  
Hematological Parameters ◽  
Inverse Correlation ◽  
Heparin Therapy ◽  
Additional Dose ◽  
Clotting Time ◽  
Post Intervention ◽  
Significant Inverse Correlation ◽  
Activated Clotting Time

Introduction: A study on 149 cardiopulmonary bypass (CPB) patients was performed to elucidate possible relationships between antithrombin (AT) activity and a subject’s clinical profile or surgery characteristics. Methods: An initial dose (300 IU/kg) of heparin was administered before CPB. Additional boluses (100 IU/kg) were administered if the activated clotting time (ACT)≤460 s. AT activity and hematological parameters were determined preoperatively, during and after CPB, and at 12, 24, 36, and 48 hours post-intervention. Results: 29.5% patients required an additional dose of heparin during CPB. Preoperative AT was 96.5 ± 13.9% in all but 4 patients. AT was significantly lower during CPB and upon leaving the operating room (59.7%-80.0%). A small, but significant, inverse correlation was observed between AT at the end of CPB and the patient’s age, as well as between basal preoperative AT and total heparin administered. Conclusions: Patient’s age could be a moderate indicator of AT activity drop and low preoperative AT activity could be a sign of reduced anticoagulant efficacy of heparin during CPB.

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.

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.

Antithrombin Concentrates in Heparin-Resistant Cardiopulmonary Bypass Patients

1996 ◽  
Vol 2 (2) ◽  
pp. 103-106 ◽  
Author(s):  
Mehraboon S. Irani
Keyword(s):  
Cardiopulmonary Bypass ◽  
Serine Protease Inhibitor ◽  
Fresh Frozen Plasma ◽  
Clotting Time ◽  
Activated Clotting Time ◽  
Heparin Resistance ◽  
Resis Tance ◽  
Fresh Frozen ◽  
Blood Transfu ◽  
Frozen Plasma

Antithrombin, a serine protease inhibitor, plays an important role in the regulation of the coagula tion cascade. It inhibits thrombin as well as factors Xa, IXa, XIa, and XIIa. Heparin markedly accelerates the rate at which antithrombin inhibits these enzymes. To prevent the formation of clots in the extracorporeal cir cuit, heparin is used during cardiopulmonary bypass sur gery (CPB). However, in a small proportion of patients, adequate anticoagulation, defined as an activated clotting time (ACT) of >400 s after an intravenous bolus of hep arin in a dose of 300 U/kg, is not achieved. Conventional treatment of heparin resistance includes fresh frozen plasma or large doses of heparin. Antithrombin concen trates were given to 12 patients who were considered to be heparin resistant at our institution. All patients had received >300 U/kg of heparin before antithrombin con centrates were infused. In all patients, the ACT pro longed to >400 s after concentrates were infused, and in nine of 12 cases to >600 s. Of these nine patients, six (67%) did not receive any allogeneic transfusions, whereas three (33%) required allogeneic blood transfu sions. In nine of 12 patients, no more heparin was given after infusing antithrombin concentrate. It appears that antithrombin concentrate, which is a fractionated, pas teurized plasma product, is a possible safer alternative to excessive heparin doses or fresh frozen plasma for CPB patients who are heparin resistant. Key Words: An tithrombin—Cardiopulmonary bypass—Heparin resis tance.

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.

Evaluation of a New Point-of-care Celite-activated Clotting Time Analyzer in Different Clinical Settings

2003 ◽  
Vol 99 (1) ◽  
pp. 54-59 ◽  
Author(s):  
Rita Paniccia ◽  
Sandra Fedi ◽  
Fiorella Carbonetto ◽  
Daniela Noferi ◽  
Paolo Conti ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Point Of Care ◽  
Factor Xa ◽  
Interventional Cardiology ◽  
Heparin Therapy ◽  
Clinical Settings ◽  
Clotting Time ◽  
New Device ◽  
Activated Clotting Time ◽  
Heparin Plasma

Background Activated clotting time (ACT) is used to monitor heparin therapy during cardiopulmonary bypass, interventional cardiology, and hemodialysis. Traditionally, ACT is performed by use of the Hemochron system. Recently, a new device, the i-STAT system, has been introduced to measure ACT. The aim of this study was to correlate the performances of these two systems and to compare ACT values with heparin levels. Methods One hundred sixty-five samples from 29 patients undergoing cardiopulmonary bypass or hemodialysis were assayed in duplicate with two Hemochron and two i-STAT devices. Heparin levels were determined by anti-factor Xa assay. Results The Hemochron ACT ranged from 88 to 1,028 s, and the i-STAT ACT ranged from 80 to 786 s. Heparin plasma levels ranged from 0.01 to 10.8 U/mL. Bland-Altman analysis showed a mean difference between the two methods of 24 +/- 101 s. Strong relationships between anti-factor Xa activity and Hemochron ACTs (r2 = 0.69, P < 0.001) and i-STAT ACTs (r2 = 0.79, P < 0.001) were observed. During cardiac surgery, significant correlations were found: Hemochron, r2 = 0.61, P < 0.001 and i-STAT, r2 = 0.74, P < 0.001. During hemodialysis, relationships between anti-factor Xa activity and ACTs were found: Hemochron, r2 = 0.62, P < 0.001 and i-STAT, r2 = 0.55, P < 0.001. Conclusions During cardiopulmonary bypass procedure and hemodialysis, i-STAT provides measurements of clotting time quite similar to Hemochron ACT, which were significantly correlated with heparin levels.

Shear-Induced Pathway of Platelet Function in Cardiac Surgery

1995 ◽  
Vol 21 (S 02) ◽  
pp. 66-70 ◽  
Author(s):  
Noriyuki Tabuchi ◽  
Izaak Tigchelaar ◽  
Willem Van Oeveren
Keyword(s):  
Cardiac Surgery ◽  
Cardiopulmonary Bypass ◽  
Platelet Function ◽  
Chest Drain ◽  
Clotting Time ◽  
Platelet Dysfunction ◽  
Excessive Bleeding ◽  
Activated Clotting Time ◽  
Proper Diagnosis

The contribution of platelet dysfunction to the impaired hemostasis after cardiac surgery remains to be established, because there is no sensitive method to assess platelet function. Measurement of the shear-induced pathway of platelet function, an important mechanism in inducing hemostasis, became possible by a novel shear-inducing technique, the in-vitro bleeding test (Thrombostat 4000). By using this test, the changes in platelet function during cardiopulmonary bypass and their contribution to hemostasis were investigated in patients undergoing cardiac surgery. Platelet function is quickly impaired shortly after the start of cardiopulmonary bypass, and partly recovered at the end of cardiopulmonary bypass. The function of aspirin-treated platelets is more severely affected than of nonaspirin platelets during cardiopulmonary bypass. Furthermore, the degree of platelet dysfunction at the end of the operation, but neither the platelet number nor the activated clotting time, was significantly correlated with blood loss from the chest drain after cardiac surgery. These results indicate the significant and variable effects of cardiopulmonary bypass on the shear-induced pathway of platelet function. Moreover, the impairment of this function of platelets appears to be a major cause of excessive bleeding in patients after cardiac surgery. Therefore, the routine use of the shear-inducing test seems helpful to make a proper diagnosis and design the therapy for bleeders after cardiac surgery.

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