Comparison of two protocols for heparin neutralization by protamine after cardiopulmonary bypass

SummaryThromboelastography (TEG) has been used after cardiopulmonary bypass (CPB) to diagnose excessive postoperative hemorrhage. Conventional TEG during CPB is not possible due to the sensitivity of the TEG to even small amounts of heparin, which produces a nondiagnostic tracing. The purpose of this study was to compare heparin neutralization using heparinase or protamine in TEG blood samples obtained during CPB. TEG testing was performed on 48 patients before, during and after CPB. Tissue plasminogen activator activity and antigen were measured on a subset of 32 patients. We found: 1) heparinase neutralized at least 10 IU/ml heparin while 1.6 ug/ml protamine neutralized up to 7 IU/ml heparin, 2) in samples with complete heparin neutralization by both methods, there was no significant difference in the R values, 3) while there was good correlation for other TEG parameters between heparinase and protamine treated samples, heparinase treatment produced shorter K values and higher angle, MA and A60, 4) while fibrinolysis was detected using both methods, heparinase treatment suppressed fibrinolysis in the TEG in both samples from patients and after in vitro addition of tissue plasminogen activator, 5) TEG was not a sensitive indicator of t-PA activity, detecting only 21% of samples with increased t-PA activity during bypass, and 5) heparinase was at least 100 times more expensive than protamine. We conclude that while both heparinase and protamine can be used to neutralize heparin in TEG samples obtained during CPB, protamine neutralization is more sensitive to fibrinolysis and less expensive, but the protamine dose must be carefully selected to match the heparin level used at individual institutions.

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Platelet dysfunction after normothermic cardiopulmonary bypass in children: Effect of high-dose aprotinin

Thrombosis and Haemostasis ◽

10.1160/th06-12-0723 ◽

2007 ◽

Vol 98 (08) ◽

pp. 385-391 ◽

Cited By ~ 3

Author(s):

Claire Flaujac ◽

Philippe Pouard ◽

Pierre Boutouyrie ◽

Joseph Emmerich ◽

Christilla Bachelot-Loza ◽

...

Keyword(s):

Cardiopulmonary Bypass ◽

Protective Effect ◽

Platelet Activation ◽

Platelet Function ◽

Pediatric Patients ◽

High Dose ◽

Platelet Dysfunction ◽

High Dose Aprotinin ◽

Marker Expression ◽

Heparin Neutralization

SummaryPlatelet dysfunction after cardiopulmonary bypass (CPB) can contribute to excessive post-operative bleeding. Most trials of the protective effect of aprotinin in this setting have involved hypothermic CPB, which is more deleterious for platelets than normothermic CPB.Here we investigated the effect of aprotinin on platelet function during normothermic CPB in pediatric patients. Twenty patients (9 newborns [<1 month old] and 11 infants [<36 month old]),weighting less than 15 kg and undergoing normothermic CPB (35–36°C) were randomly assigned to two equal groups,one of which received high-dose aprotinin.Platelet function was assessed by flow cytometry just before CPB and 5 minutes after heparin neutralization. F1+2 fragments were measured by ELISA before and 5 minutes after CPB. Platelet activation marker expression (CD62P and activated αIIbβ3) induced by ADP or TRAP was lower after CPB than before CPB, suggesting a deleterious effect of normothermic CPB on platelet function. Prothrombin fragment F1+2 levels increased after CPB. Aprotinin administration did not influence the level of prothrombin fragments or platelet marker expression measured in basal condition. However, after CPB, the capacity for platelet activation was higher in the aprotinin group, as shown by measuring CD62P expression afterTRAP activation (p=0.05).This study suggests that pediatric normothermic CPB causes platelet dysfunction, and that high-dose aprotinin has a protective effect.

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PROLONGED PT AND PTT DESPITE ADEQUATE HEPARIN NEUTRALIZATION FOLLOWING CARDIOPULMONARY BYPASS IN CHILDREN

Anesthesiology ◽

10.1097/00000542-198709001-00022 ◽

1987 ◽

Vol 67 (3) ◽

pp. A22-A22 ◽

Cited By ~ 1

Author(s):

T. H. Oh ◽

C. Bell ◽

C. Hughes

Keyword(s):

Cardiopulmonary Bypass ◽

Heparin Neutralization

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Estimating the rate of thrombin and fibrin generation in vivo during cardiopulmonary bypass

Blood ◽

10.1182/blood-2002-08-2400 ◽

2003 ◽

Vol 101 (11) ◽

pp. 4355-4362 ◽

Cited By ~ 61

Author(s):

Wayne L. Chandler ◽

Tomas Velan

Keyword(s):

Cardiopulmonary Bypass ◽

Thrombin Generation ◽

Vascular System ◽

Ischemic Heart ◽

Generation Rate ◽

Steady Increase ◽

Soluble Fibrin ◽

Baseline Levels ◽

Heparin Neutralization

Abstract Our objective was to estimate the in vivo rates of thrombin and fibrin generation to better understand how coagulation is regulated. Studied were 9 males undergoing cardiopulmonary bypass (CPB). The rates of thrombin, total fibrin, and soluble fibrin generation in vivo were based on measured levels of prothrombin activation peptide F1.2, thrombin-antithrombin complex, fibrinopeptide A, and soluble fibrin, combined with a computer model of the patient's vascular system that accounted for marker clearance, hemodilution, blood loss, and transfusion. Prior to surgery, the average thrombin generation rate was 0.24 ± 0.11 pmol/s. Each thrombin molecule in turn generated about 100 fibrin molecules, of which 1% was soluble fibrin. The thrombin generation rate did not change after sternotomy or administration of heparin, then rapidly increased 20-fold to 5.60 ± 6.65 pmol/s after 5 minutes of CPB (P = .000 05). Early in CPB each new thrombin generated only 4 fibrin molecules, of which 35% was soluble fibrin. The thrombin generation rate was 2.14 ± 1.88 pmol/s during the remainder of CPB, increasing again to 5.47 ± 4.08 pmol/s after reperfusion of the ischemic heart (P = .000 08). After heparin neutralization with protamine, thrombin generation remained high (5.34 ± 4.01 pmol/s, P = .0002) and total fibrin generation increased, while soluble fibrin generation decreased. By 2 hours after surgery, thrombin and fibrin generation rates were returning to baseline levels. We conclude that cardiopulmonary bypass and reperfusion of the ischemic heart results in bursts of nonhemostatic thrombin generation and dysregulated fibrin formation, not just a steady increase in thrombin generation as suggested by previous studies.

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