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Perumal Thiagarajan Lab

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The Perumal Thiagarajan Lab is exploring the cause and consequences of anionic phospholipid exposure in blood cells.

Anionic phospholipids, such as phosphatidylserine, are normally present in the inner leaflet of membrane bilayer. Transbilayer movement of phosphatidylserine occurs during apoptosis, cellular senescence and during platelet activation. Exposure of phosphatidylserine in platelets is accompanied by the generation of platelet-derived microvesicles.

Microvesicles are also generated from other blood cells such as macrophages and endothelial cells during apoptosis and they are present in normal plasma. Deficiency of anionic phospholipid exposure and microvesiculation in platelets leads to an inherited bleeding disorder (Scot syndrome). Increased microvesicles have been detected in the circulation in patients with disseminated intravascular coagulation, heparin-induced thrombocytopenia, the antiphospholipid antibody syndrome, transient ischemic attacks, and thrombotic thrombocytopenic purpura, all conditions associated with either arterial or venous thrombosis.

These associations suggest that, while they may be necessary for normal hemostasis, elevated microvesicles concentrations could predispose to thrombosis. Clearly, a homeostatic mechanism must exist to balance the generation of anionic phospholipids by providing for their clearance, which when perturbed will enhance the risk of thrombosis.

We are investigating defects in the clearance of microvesicles as a cause of hypercoagulable state.