Scott syndrome

Scott syndrome
Classification and external resources
OMIM 262890
DiseasesDB 32153
MeSH C563120

Scott syndrome is a rare congenital bleeding disorder that is due to a defect in a platelet mechanism required for blood coagulation.[1]

Normally when a vascular injury occurs, 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).[2]

In Scott syndrome, the mechanism for translocating PS to the platelet membrane is defective, resulting in impaired thrombin formation.[3][4][5] 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,[6] that may be involved in this process appears to be normal in Scott syndrome platelets.[7] Other possible defects in PS translocation, reported in some patients, require further study.[8] The initially reported patient with Scott Syndrome has been found to have a mutation at a splice-acceptor site of the gene encoding transmembrane protein 16F (TMEM16F).[9] At present, the only treatment for episodes of bleeding is the transfusion of normal platelets.

References

  1. ↑ Weiss HJ. Scott syndrome: a disorder of platelet coagulant activity (PCA). Sem Hemat 1994; 31:312-319
  2. ↑ 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
  3. ↑ Rosing J, Bevers EM, Comfurius P, Hemker HC, 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.
  4. ↑ 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; 87:1409-1415
  5. ↑ Elliott 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
  6. ↑ Sims PJ, Wiedmer T. Unraveling the mysteries of phospholipid scrambling. Thromb Haemost 2001; 86:266-275
  7. ↑ 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
  8. ↑ Weiss, HJ: Impaired platelet procoagulant mechanisms in patients with bleeding disorders. Sem. Thromb. Hemost. 35:233-241, 2009
  9. ↑ Suzuki J, Umeda M, Sims PJ, Nagata S. Calcium-dependent phospholipid scrambling by TMEM16F. Nature online, November 24, 2010

Further reading

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