The value of the thromboelastometry heparinase assay (HEPTEM) in cardiac surgery

2015 ◽  
Vol 114 (11) ◽  
pp. 1058-1063 ◽  
Author(s):  
Marcus Daniel Lancé ◽  
Robin van der Steeg ◽  
Christa Boer ◽  
Michael Isaäc Meesters

SummaryThe thromboelastometry INTEM clotting time (CT) with heparinase (HEPTEM) is frequently used to detect residual heparin after cardiopulmonary bypass (CPB) in cardiac surgery. This study investigated whether the HEPTEM CT reflects the presence of residual heparin and the association of the protamine-to-heparin ratio to the INTEM and HEPTEM CT. We retrospectively evaluated thromboelastometry data that were obtained before CPB and after protamine infusion following CPB in two tertiary hospitals. The number of patients with an INTEM:HEPTEM ratio (IH-ratio) > 1, suggesting residual heparin, were quantified. Moreover, the influence of different protamine-to-heparin-dosing-ratios (P:H) on the INTEM and HEPTEM CT was evaluated in the clinical setting and in blood drawn from healthy volunteers. An INTEM:HEPTEM CT ratio > 1.1 was observed in 16% of the patients prior to CPB, and in 15% after protamine administration. Interestingly, 23% and 36% of the patients had an HEPTEM CT exceeding the INTEM CT before CPB and following protamine administration. The HEPTEM CT was longer than the INTEM CT in patients with a P:H-ratio of 1:1 (265 ± 132 vs 260 ± 246 s; p=0.002) or P:H-ratio of 1.3:1 (357 ± 174 vs 292 ± 95 s; p=0.001). Increasing P:H-ratios induced a prolonged HEPTEM CT in fresh blood. In conclusion, limited agreement was observed between INTEM and HEPTEM clotting time in the absence of heparin. INTEM comparison to HEPTEM may not always reliably reflect the presence of residual heparin, while protamine may additionally affect the latter test. These observations complicate HEPTEM results interpretation in clinical situations with suspected residual heparin effect after protamine.

2017 ◽  
Vol 46 (2) ◽  
pp. 873-882 ◽  
Author(s):  
Jung Min Lee ◽  
Eun Young Park ◽  
Kyung Mi Kim ◽  
Jong Chan Won ◽  
Tack Koon Jung ◽  
...  

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The ACT was checked at baseline with both devices after inducing anaesthesia, and 400 to 800 mL of whole blood was withdrawn to induce moderate ANH.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.


2000 ◽  
Vol 23 (5) ◽  
pp. 319-324 ◽  
Author(s):  
A. Cazzaniga ◽  
M. Ranucci ◽  
G. Isgrò ◽  
G. Soro ◽  
D. De Benedetti ◽  
...  

139 patients undergoing cardiac surgery were included in a prospective, randomized trial. Patients were randomly allocated to receive cardiopulmonary bypass (CPB) with Trillium™ Biopassive Surface (TBS Group) coated oxygenators or conventional circuits (control group). 112 patients were studied with respect to postoperative biochemical profile; a subgroup of 27 patients was studied with respect to perioperative complement (C3a) activation. Patients in the TBS group demonstrated a significantly lower white blood cell count at the end of the operation (p=0.036) and a significantly higher platelet count the day after the operation (p=0.023) when compared to the control group. C3a was significantly higher (p=0.02) in the TBS group after 30 minutes of CPB, but the C3a increase after protamine administration was significantly less pronounced in the TBS group vs. the control group. Further studies involving platelet and leukocyte activation are required to better elucidate the action of this new coating in the setting of routine CPB.


Perfusion ◽  
2020 ◽  
pp. 026765912094935
Author(s):  
Han Li ◽  
Cyril Serrick ◽  
Vivek Rao ◽  
Paul M Yip

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.


Perfusion ◽  
2020 ◽  
pp. 026765912092608
Author(s):  
Alfred H Stammers ◽  
Stephen G Francis ◽  
Randi Miller ◽  
Anthony Nostro ◽  
Eric A Tesdahl ◽  
...  

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.


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 ◽  
...  

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.


2018 ◽  
Vol 23 (2) ◽  
pp. 237-247 ◽  
Author(s):  
Malak Maharramova ◽  
Katherine Taylor

Objectives. In pediatric cardiac surgery, does caudal anesthesia promote early extubation, reduce pain scores, reduce stress responses, and length of stay (LOS)? Design. A systematic review. Participants. Inclusion criteria included cardiac surgical procedures (with or without cardiopulmonary bypass) in any subject between the ages of full-term newborn and 18 years receiving caudal anesthesia of any medication combination. Searches were conducted with assistance of an Academic librarian from 1947 to July 2017. Methods. Relevant studies selected were randomized trials or cohort studies. Results. The total number of patients was 2159 in 17 studies. There were 8 prospective randomized clinical trials and 9 cohort studies. Caudal medications included dexmedetomidine, bupivacaine, sufentanil, morphine, fentanyl, and neostigmine. Nine studies reported earlier extubation in patients with caudal anesthesia. Cardiopulmonary bypass and surgical duration mitigated early extubation anesthetic strategies. Three of 5 studies showed reduced pain scores and need for opiates, 2 studies showed no difference. Two of 3 studies showed a reduction in stress response. Hemodynamic assessments were improved in 2 studies and unchanged in 3 studies. Four studies showed reduced hospital LOS. Studies are difficult to interpret because of the comparative techniques used. Conclusions. The data quality in this review is too poor to make recommendations regarding incorporation of caudal anesthesia into clinical practice. Caudal anesthesia may be favorable for early extubation, improved pain, and hemodynamics and reduced LOS. There are many other anesthetic alternatives to facilitate early extubation. Our review is limited by heterogeneous populations, variable pain measurement scales, and absent definitions of extubation indicators.


Perfusion ◽  
2011 ◽  
Vol 26 (6) ◽  
pp. 487-495 ◽  
Author(s):  
V Muedra ◽  
S Bonanad ◽  
M Gómez ◽  
V Villalonga ◽  
F Sánchez ◽  
...  

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.


2002 ◽  
Vol 97 (4) ◽  
pp. 837-841 ◽  
Author(s):  
Andreas Koster ◽  
Thomas Fischer ◽  
Michael Praus ◽  
Helmut Haberzettl ◽  
Wolfgang M. Kuebler ◽  
...  

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 ( &lt; 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.


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