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Early Heparin Administration Increases Plasma Tissue Factor Pathway Inhibitor and Attenuates Tissue Factor Mediated Thrombin Generation During Simulated Cardiopulmonary Bypass
Author(s) -
Morizumi Sei,
Hiramatsu Yuji,
Matsuzaki Kanji,
Sato Shoko,
Abe Masakazu,
Sakakibara Yuzuru,
Matsushita Shonosuke
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.lb459
Subject(s) - tissue factor pathway inhibitor , heparin , tissue factor , cardiopulmonary bypass , medicine , thrombin , coagulation , anesthesia , pharmacology , platelet
Background We tested the hypothesis that early treatment with heparin prior to the emergence of tissue factor (TF) would boost plasma tissue factor pathway inhibitor (TFPI) levels and attenuate TF mediated thrombin generation during simulated cardiopulmonary bypass (CPB). Methods Four study groups were examined: Control group (heparin 3.75 U/ml blood, n=7), rTF group (heparin + recombinant human TF 1000 pg/ml, n=7), TFPI boost group (heparin, in pre‐heparinized donor blood, n=8), and TFPI boost + rTF group (heparin + rTF, in pre‐heparinized donor blood, n=7). In the two TFPI boost groups, 50U/kg of heparin was given to the donors intravenously five minutes before donation to elevate plasma TFPI levels. Results Pre‐heparinization increased total plasma TFPI levels by a factor of 8.0 when compared to non‐heparinized donor blood. Administration of rTF significantly enhanced the generation of prothrombin fragment (F1 {2) (p<0.0001). The boost of TFPI reduced F1+2 to Control group levels in TFPI boost + rTF group (p=0.0178), and in TFPI boost group (p<0.0001 ). Conclusions Heparin induced TFPI elevation results in attenuation of tissue factor mediated thrombin generation during simulated CPB. Early heparin administration prior to emergence of plasma TF may represent a novel strategy for the control of thrombin generation initiated by extrinsic coagulation pathway during CPB.