Antithrombin deficiency increases thrombin activity after prolonged cardiopulmonary bypass.
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 Thrombinoscope 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).


CONCLUSIONS
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.
Sniecinski
Roman
R
Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia, USA.
Szlam
Fania
F
Chen
Edward P
EP
Bader
Stephen O
SO
Levy
Jerrold H
JH
Tanaka
Kenichi A
KA
D000368:Aged; D000991:Antithrombins / Q000172:deficiency*; D001777:Blood Coagulation; D006348:Cardiac Surgical Procedures; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D050792:Circulatory Arrest, Deep Hypothermia Induced / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013917:Thrombin / Q000378:metabolism*; D013927:Thrombosis / Q000097:blood / Q000209:etiology*; D013997:Time Factors; D065227:Transfusion Reaction
D000991:Antithrombins; D013917:Thrombin