Professor John Weisel, U. Pennsylvania Perelman School of Medicine, “Blood clot contraction: Mechanisms, pathophysiology, and disease” (hosts: M. Guthold and S. Baker)

Thursday, January 12, 2023 4pm to 5pm

NOTE: THIS IS A PAST EVENT
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Abstract:

The focus of this talk will be on blood clot contraction (also called retraction), an important aspect of blood clotting driven by activated platelets and causing compaction of fibrin along with compression of the embedded red blood cells. As a lesson in scientific research, I will start by describing the serendipitous discovery that led my group to study this subject. The consequences of clot contraction include redistribution of the fibrin-platelet meshwork toward the periphery of the clot and condensation of erythrocytes in the core, followed by their deformation from biconcave into polyhedral cells (polyhedrocytes). These structural signatures of contraction have been found in ex vivo human thrombi derived from various locations, indicating that clots undergo intravital contraction within blood vessels. In hemostatic clots, tightly packed polyhedrocytes make a nearly impermeable seal that stems bleeding, and this is impaired in hemorrhagic disorders. In thrombosis, contraction facilitates the local blood flow by decreasing thrombus obstructiveness, reducing permeability, and changing the susceptibility to fibrinolytic enzymes that digest clots. However, in (pro)thrombotic conditions, continuous background platelet activation is followed by platelet exhaustion, refractoriness, and impaired intravital clot contraction, which is associated with weaker thrombi predisposed to embolization. Therefore, assays that detect imperfect in vitro clot contraction have potential diagnostic and prognostic value for imminent or ongoing thrombosis and thrombotic embolism. Altogether, contraction of blood clots and thrombi is an underappreciated and understudied process that has a pathogenic and clinical significance in bleeding and thrombosis of various etiologies.

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**Refreshments will be served in the Olin lounge beginning at 3:30 pm.

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