Combined anticoagulation protocol using TFPI, antithrombin and thrombomodulin during cardiopulmonary bypass

2014 Fiscal Year Final Research Report

• Project/Area Number: 23390332
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cardiovascular surgery
• Research Institution: University of Tsukuba
• Principal Investigator: HIRAMATSU Yuji 筑波大学, 医学医療系, 教授 (30302417)
• Co-Investigator(Kenkyū-buntansha): AGEYAMA Naohide 独立行政法人医薬基盤研究所, 霊長類医科学センター, 研究員 (50399458) ; SAKAKIBARA Yuzuru 筑波大学, 医学医療系, 教授 (60192085) ; HASEGAWA Yuichi 筑波大学, 医学医療系, 准教授 (00251059) ; GOTO Yukinobu 筑波大学, 医学医療系, 講師 (20451700)
• Project Period (FY): 2011-04-01 – 2015-03-31
• Keywords: 体外循環 / トロンビン / 組織因子 / 外因系凝固 / 内因系凝固 / TFPI / アンチトロンビン / トロンボモジュリン

Outline of Final Research Achievements

We aimed to establish a new anticoagulation protocol during cardiopulmonary bypass (CPB). Our hypothesis was that administration of high-dose heparin causes massive release of tissue factor pathway inhibitor (TFPI) from endothelial cells, and antithrombin or thrombomodulin provides additional thrombin inhibition. We performed experiments using primate (Macaca fascicularis, 5kg) CPB model. Plasma TFPI was enhanced by pre-heparinization, and levels of thrombin generation were reduced through inhibition of extrinsic pathway when compared with control group. Inhibition of thrombin generation was further enhanced by the addition of antithrombin and thrombomodulin. Anti-inflammatory effects of either drug were not revealed in our anticoagulation protocol. Combined anticoagulation protocol with TFPI, antithrombin and thrombomodulin may be a promising alternative to heparin toward inhibition of both intrinsic and extrinsic pathways during CPB.

Free Research Field

心臓血管外科学