Scott syndrome

 ( Coagulopathies ) 

Scott syndrome is a rare congenital bleeding disorder that is due to a defect in a platelet mechanism required for blood coagulation.Weiss HJ. Scott syndrome: a disorder of platelet coagulant activity (PCA). Sem Hemat 1994; 31:312–319

Normally when a vascular injury occurs (i.e., a cut, scrape or other injury that causes bleeding), platelets are activated and phosphatidylserine (PS) in the inner leaflet of the platelet membrane is transported to the outer leaflet of the platelet membrane, where it provides a binding site for plasma protein complexes that are involved in the conversion of prothrombin to thrombin, such as factor VIIIa-IXa (tenase) and factor Va-Xa (prothrombinase).Zwaal FA, Comfurius P, Bevers EM. Scott syndrome, a bleeding disorder caused by defective scrambling of membrane phospholipids. Biochem Bioph Acta 2004; 1636:119–128

In Scott syndrome, the mechanism for translocating PS to the platelet membrane is defective, resulting in impaired thrombin formation.Rosing J, Bevers EM, Comfurius P, Coen Hemker, von Dieijen G, Weiss HJ, et al. Impaired factor X and prothrombin activation associated with decreased phospholipid exposure in platelets from a patient with a bleeding disorder. Blood 1985; 65:1557–1561.Toti F, Satta N, Fressinaud E, Meyer D, Freyssinet JM. Scott syndrome, characterized by impaired transmembrane migration of procoagulant phosphatidylserine and hemorrhagic complications, is an inherited disorder. Blood 1996; 87:1409-1415Elliott JI, Mumford AD, Albrecht C, Collins PW, Giddings JC, Higgins CF et al. Characterization of lymphocyte responses to Ca2+ in Scott syndrome. Thromb Haemost 2004; 91:412-415 A similar defect in PS translocation has also been demonstrated in Scott syndrome red blood cells and Epstein–Barr virus transformed lymphocytes, suggesting that the defect in Scott syndrome reflects a mutation in a stem cell that affects multiple hematological lineages.

The basis for the defect in PS translocation is, at present, unknown. A candidate protein, scramblase,Sims PJ, Wiedmer T. Unraveling the mysteries of phospholipid scrambling. Thromb Haemost 2001; 86:266–275 that may be involved in this process appears to be normal in Scott syndrome platelets.Zhou Q, Sims PJ, Wiedmer T. Expression of proteins controlling transbilayer movement of plasma membrane phospholipids in the B lymphocytes from a patient with Scott syndrome. Blood 1998; 92:1707–1712 Other possible defects in PS translocation, reported in some patients, require further study.Weiss, HJ: Impaired platelet procoagulant mechanisms in patients with bleeding disorders. Sem. Thromb. Hemost. 35:233–241, 2009 The initially reported patient with Scott syndrome has been found to have a mutation at a splice-acceptor site of the gene encoding anoctamin 6 (ANO6, transmembrane protein 16F, TMEM16F).Suzuki J, Umeda M, Sims PJ, Nagata S. Calcium-dependent phospholipid scrambling by TMEM16F. Nature online, November 24, 2010 At present, the only treatment for episodes of bleeding is the transfusion of normal platelets.

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