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Anesth Analg 2008; 106:713-718
© 2008 International Anesthesia Research Society
doi: 10.1213/ane.0b013e3181608f7c
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CARDIOVASCULAR ANESTHESIOLOGY

Antithrombin Deficiency Increases Thrombin Activity After Prolonged Cardiopulmonary Bypass

Roman Sniecinski, MD*, Fania Szlam, MMSc*, Edward P. Chen, MD{dagger}, Stephen O. Bader, MD*, Jerrold H. Levy, MD*, and Kenichi A. Tanaka, MD, MSc*

From the Departments of *Anesthesiology, and {dagger}Surgery (Cardiothoracic), Emory University School of Medicine, Atlanta, Georgia.

Address correspondence and reprint requests to Kenichi A. Tanaka, MD, MSc, Division of Cardiothoracic Anesthesia, Department of Anesthesiology, 1364 Clifton Rd., NE, Atlanta, GA 30322. Address e-mail to kenichi.tanaka{at}emoryhealthcare.org.

Abstract

BACKGROUND: Antithrombin (AT) levels decrease during cardiopulmonary bypass (CPB), particularly when combined with deep hypothermic circulatory arrest (DHCA). Low AT levels might lead to imbalance of pro- and anticoagulant factors promoting systemic thrombotic events. We hypothesized that low levels of AT might lead to increased in vitro thrombin generation when procoagulant factors are added to the patient's plasma after CPB.

METHODS: Blood samples were obtained before heparinization and after separation from CPB from five patients undergoing cardiac surgery with DHCA. AT levels were determined by chromogenic assay and expressed as a percent of normal activity. The balance between procoagulant and anticoagulant elements was manipulated in the patients' plasma by adding normal donor plasma, AT-deficient plasma, or purified AT. The ThrombinoscopeTM system was used to evaluate thrombin generation with and without AT supplementation.

RESULTS: AT levels (median, range) were 82.0% (71.0, 109) and 37.0% (34.0, 41.0) of normal before and after separation from CPB, respectively (P < 0.05). Peak thrombin generation (median, range) was 56.6 nM (42.1, 61.0) in plasma after CPB, and it remained at 61.1 nM (54.9, 64.5) when a donor plasma with normal AT (105%) was added. When AT-deficient plasma was added to the patient's plasma, peak thrombin generation (median, range) was increased from 56.6 nM (42.0, 61.0) to 117 nM (95.0, 188) (P < 0.05 versus control). After the addition of purified AT, the peak thrombin generation was reduced to 12.2 nM (9.0, 29.3) (P < 0.05 versus control).

CONCLUSION: Plasma AT activity is severely decreased after CPB with DHCA. Our data suggest that the administration of coagulation factor components without AT repletion may lead to excessive thrombin generation, which clinically, may potentially lead to a hypercoagulable state.







Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 2008 by the International Anesthesia Research Society.