正常妊娠経過中の血漿von Willebrand因子と高ずり応力惹起血小板凝集とに関する研究

Abstract

Plasma von Willebrand factor (vWF) plays a central role in platelet adhesion and platelet thrombi formation under high shear stress. Thereby, the elevated plasma level of vWF during normal pregnancy has a risk of serious thrombo-embolic complications, but such events rarely happen. To address this issue, I have studied the structural and functional aspects of plasma vWF on 74 different samples from normal non- pregnant women and on 217 samples from 157 normal pregnant women, both after taking informed consent. Biological function of vWF was measured by platelet aggregation activities in the presence of an antibiotic ristocetin (RCof) and a snake venom botrocetin (BCof), and by high shear stress-induced platelet aggregation (H-SIPA), together with the measurements of vWF antigen (vWF : Ag) levels and vWF-multimer analysis. The increase of RCof was superior to that of BCof and vWF:Ag, regardless of ABO phenotypes. At full term, the respective values (M±SD) were 370±171% for RCof, 237 ± 89% for BCof, and 197±39% for vWF : Ag. In accord with this result, the ratio of high molecular weight (HMW)-vWF multimers increased. It is generally accepted that HMW-vWF multimers have higher biological activities than other multimers. However, H-SIPA of normal pregnant women was not enhanced and rather weakened when platelet rich plasmas were tested. This paradoxical result was also confirmed using normal washed platelets mixed with fresh plasmas of normal pregnant women. Interestingly, H-SIPA was remarkably enhanced when normal washed platelets were mixed with plasmas of pregnant women which were frozen at -80℃ for 7 days and thawed at 37℃. Such 'freezing-thawing' effect on H-SIPA was not seen in plasmas of normal non-pregnant women. Taking these results together, it was suggested that plasmas of normal pregnant women contain the 'frozen-labile' substance(s) which regulates H- SIPA against the quantitatively elevated and qualitatively HMW-mulitimer dominant status of plasma vWF.