Pathophysiology of acute graft-versus-host disease from the perspective of hemodynamics determined by dielectric analysis.

Abstract

Numerous reports have demonstrated that the pathophysiology of graft-versus-host disease (GVHD) during hematopoietic stem cell transplantation (HSCT) is closely related to vascular endothelial disorders and coagulation abnormalities. We previously presented the discovery of a principle and the development of a novel instrument for measuring whole blood coagulation. This was achieved by assessing the variations in the dielectric properties of whole blood. To investigate how GVHD affects the changes of dielectric properties of whole blood in patients with HSCT. We examined the changes of dielectric properties of whole blood and erythrocyte proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis sequentially in patients with HSCT and compared it with clinical symptoms and inflammatory parameters of GVHD. During severe GVHD, the dielectric relaxation strength markedly increased and expression of band3 decreased. The dielectric relaxation strength normalized with the improvement of GVHD. In vitro analysis confirmed that the increase of relaxation strength was associated with severe erythrocyte aggregates, but not with decreased expression of band3. Severe erythrocyte aggregates observed in GVHD may cause coagulation abnor malities and circulatory failure, which, together with the irreversible erythrocyte dysfunction we recently reported, could lead to organ failure.