Shapes and Dimensions of Blood Clots Affect the Rate and Extent of Platelet-Driven Clot Contraction and Will Determine the Outcomes of Thrombosis

Abstract

BackgroundContraction (retraction, shrinkage) of hemostatic blood clots and obstructive thrombi is an important pathophysiological process. To mimic thrombi of various locations, we sought to determine whether the initial shape and dimensions of blood clots affect the rate and extent of clot contraction. MethodsThrombin-induced clots were formed in 0.3-5.7 ml samples of citrated human blood or platelet-rich plasma in a cylinder, cuboid, or flat chamber. The clots were allowed to contract at 37{degrees}C for 60 minutes with shrinkage tracked photographically. Following complete contraction, the physiologically most relevant cylindrical clots of various initial volumes (0.5 ml or 1.5 ml) were analyzed with scanning electron microscopy for composition and spatial non-uniformity with the emphasis on compressed polyhedral erythrocytes (polyhedrocytes). ResultsWith the same volumes studied, the rates and final extents of contraction of whole blood clots were shape-dependent in the following order: flat > cuboid = cylindrical. Irrespective of the shape, the initially smaller clots always contracted to a larger extent. Unlike clots in whole blood, the platelet-rich plasma clots contracted almost independently of the clot volumes and shapes studied, indicating a key role of erythrocytes. The smaller blood clots with a higher extent of contraction contained more relative volume fraction of erythrocytes, especially compressed polyhedrocytes, due to tight packing and a decrease in the intercellular space. Unlike the smaller clots, the larger clots were not clearly segregated into distinct layers, reflecting incomplete spatial redistribution of blood clot components typical for contraction. ConclusionsContraction of blood clots depends on their shape and size. The smaller and larger clots have distinct size-dependent rates and extents of contraction as well as degrees of structural non-uniformity, reflecting different spatial gradients of compressive stresses. The physiological relevance of these findings is related to the variable geometry and size of intravascular blood clots and thrombi.