Both TMEM16F-dependent and TMEM16F-independent pathways contribute to phosphatidylserine exposure in platelet apoptosis and platelet activation.

Scott syndrome, a bleeding disorder caused by defective phospholipid scrambling, has been associated with mutations in the TMEM16F gene. The role of TMEM16F in apoptosis- or agonist-induced phosphatidylserine (PS) exposure was studied in platelets from a Scott syndrome patient and control subjects. Whereas stimulation of control platelets with the BH3-mimetic ABT737 resulted in 2 distinct fractions with moderate and high PS exposure, the high PS-exposing fraction was markedly delayed in Scott platelets.

Ribavirin-induced externalization of phosphatidylserine in erythrocytes is predominantly caused by inhibition of aminophospholipid translocase activity.

Ribavirin in combination with interferon-α is the standard treatment for chronic hepatitis C, but often induces severe anemia forcing discontinuation of the therapy. Whereas suppression of bone marrow by interferon may impact on the production of erythrocytes, it has been suggested that accumulation of ribavirin in erythrocytes induces alterations causing an early removal of these cells by the mononuclear phagocytic system. Externalization of phosphatidylserine, which is exclusively present in the cytoplasmic leaflet of the plasma membrane, is a recognition signal for phagocytosis in particular of apoptotic cells.

Hyperglycemia accelerates arterial thrombus formation and attenuates the antithrombotic response to endotoxin in mice.

Recent human studies reveal that hyperglycemia induces procoagulant and antifibrinolytic effects in blood that may contribute to a greater risk of arterial thrombosis, but the direct relationship between high blood glucose levels and thrombosis has not yet been investigated. We performed a number of experiments to clarify whether hyperglycemia was causally related to arterial thrombosis and whether the combined stimulus of hyperglycemia and inflammation would enhance the thrombotic effect. In a model of ferric-chloride-induced carotid artery thrombosis, hyperglycemia did not influence the time to occlusion in mice pretreated with streptozotocin, but the rate of thrombus formation was accelerated.

Reversible inhibition of the platelet procoagulant response through manipulation of the Gardos channel.

The platelet procoagulant response requires a sustained elevation of the intracellular Ca2+ concentration, [Ca2+]i, causing exposure of phosphatidylserine (PS) at the outer surface of the plasma membrane. An increased [Ca2+]i also activates Ca2+-dependent K+ channels. Here, we investigated the contribution of the efflux of K+ ions on the platelet procoagulant response in collagen-thrombin-activated platelets using selective K+ channel blockers.

Influence of erythrocyte shape on the rate of Ca2+-induced scrambling of phosphatidylserine.

Membrane-perturbing agents that cause transformation of biconcave erythrocytes into echinocytes or stomatocytes were used to investigate the influence of erythrocyte shape on the rate of Ca(2+)-induced scrambling of phospholipids. Erythrocytes were treated with a variety of lipid-soluble compounds to induce these shape changes, followed by incubation with calcium and ionomycin to activate lipid scramblase. Prothrombinase activity of the cells was used to monitor the rate of surface exposure of phosphatidylserine, which is taken as a measure of scramblase activity.