Thrombin production, inactivation and expression during open heart surgery measured by assays for activation fragments including a new ELISA for prothrombin fragment F1 + 2.

Abstract:

:Activation of coagulation was studied during the peri-operative period in patients undergoing cardiopulmonary bypass (CPB) surgery using activation markers which have recently become available: prothrombin fragment F1 + 2 (F1 + 2), which is a measure of total thrombin generation, and thrombin-antithrombin complex, which is a measure of inactivation of free thrombin by antithrombin. Levels of the specific marker of fibrin breakdown, D-dimer, were also determined. F1 + 2 levels were assessed using a newly developed ELISA described herein which employs a neoantigen-specific capture antibody raised using a synthetic peptide; the latter antibody has been pre-adsorbed against prothrombin to ensure high specificity for F1 + 2. Increased generation of thrombin during surgery was clearly demonstrated despite maintenance of a high concentration of heparin during the period of extracorporeal blood circulation. There was a close association (r = 0.882) between the generation of thrombin (F1 + 2 levels) and its inhibition (TAT levels). Differences were noted, however, between the information provided by F1 + 2 and TAT, which are interpreted with regard to the different in vivo fates of F1 + 2 and thrombin. The enhanced activation and inhibition of coagulation observed during CPB was suppressed once physiological blood circulation was restored, with F1 + 2 returning to pre-surgical levels within 24 h after surgery. During the post-operative period D-dimer levels, which rose in concert with F1 + 2 and TAT levels, remained highly elevated, suggesting that not all of the generated thrombin was inactivated by antithrombin.(ABSTRACT TRUNCATED AT 250 WORDS)

journal_name

Thromb Haemost

authors

Boisclair MD,Lane DA,Philippou H,Sheikh S,Hunt B

subject

Has Abstract

pub_date

1993-08-02 00:00:00

pages

253-8

issue

2

eissn

0340-6245

issn

2567-689X

journal_volume

70

pub_type

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