Platelet and vascular endothelial function in the pathogenesis of acquired VW disease after VAD therapy

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10745
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular surgery
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: MIZUNO Toshihide 国立研究開発法人国立循環器病研究センター, 研究所, 室長 (40426515)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 補助人工心臓 / 後天性フォンビルブランド病 / 血小板機能 / 血管内皮機能 / 血液凝固能

Outline of Final Research Achievements

In this study, A simple mock circulation test　(5L/min, 100 mmHg) was performed to investigate with both whole-blood samples and platelet-poor plasma (PPP) using fresh bovine blood. High-molecular-weight multimers (HMWMs) in VWF are reduced immediately after the initiation of blood circulation using the axial flow pump, and it had plateaued 60 minutes later. In the study using a centrifugal pump, cleavage of the HMWMs compared to that in the case of using a centrifugal pump was very slight. Moreover, in the whole-blood sample study, HMWMs reduced once, and it had been observed to recover after 60 minutes. However, HMWMs in the PPP sample was observed to reduce continuously during a circulation test. The dynamics of VWF within the blood pump was shown to depend on the type of the blood pump, and this study demonstrated that re-supply of VWF due to platelet activation and cleavage of VWF due to shear stress in the pump occurred at the same time by circulating within the blood pump.

Free Research Field

人工臓器学

Academic Significance and Societal Importance of the Research Achievements

VAD装着後の後天性VW病は，術後遠隔期の出血性素因として注目されているが，その病理学的機序は明らかになっていない．現在までの研究では，この後天性VW病におけるVWF高分子量マルチマーの切断現象に関してポンプ内の物理的要因による機序に注目が集まっているが，その病態の多様性を考慮すると，生体内からのVWFの再供給が本病態に大きく係わっていることが新たに予想された．しかしながら，このような観点での研究は，現時点ではほとんどされておらず，本研究によりVAD装着後の出血性合併症の本態が解明され，成果が患者へ還元されれば，VAD症着後の出血性合併症の診断，治療に大きく寄与できるものと考えた．