Scott's syndrome
Encyclopedia
Scott syndrome is a rare congenital bleeding disorder that is due to a defect in a platelet
mechanism required for blood coagulation
. When normal platelets are activated, as may occur at sites of vascular injury, phosphatidylserine (PS) in the inner leaflet of the platelet membrane is transported to the outer membrane surface of the platelet, where it provides a binding site for plasma protein complexes, such as factor VIIIa-IXa (tenase
) and factor Va-Xa (prothrombinase
), that are involved in the conversion of prothrombin to thrombin
. In Scott syndrome, the mechanism for translocating PS to the platelet membrane is defective, resulting in impaired thrombin
formation. 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 effects multiple hematological lineages. The basis for the defect in PS translocation is, at present, unknown. A candidate protein, scramblase
, that may be involved in this process appears to be normal in Scott syndrome platelets. Other possible defects in PS translocation, reported in some patients, require further study. 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.
Platelet
Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days...
mechanism required for blood coagulation
Coagulation
Coagulation is a complex process by which blood forms clots. It is an important part of hemostasis, the cessation of blood loss from a damaged vessel, wherein a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop bleeding and begin repair of the damaged vessel...
. When normal platelets are activated, as may occur at sites of vascular injury, phosphatidylserine (PS) in the inner leaflet of the platelet membrane is transported to the outer membrane surface of the platelet, where it provides a binding site for plasma protein complexes, such as factor VIIIa-IXa (tenase
Tenase
In coagulation, the procoagulant protein factor X can be activated into factor Xa two ways. Extrinsic and intrinsic ways.The activating complexes are called tenase...
) and factor Va-Xa (prothrombinase
Prothrombinase
The prothrombinase complex consists of the serine protease, Factor Xa, and the protein cofactor, Factor Va. The complex assembles on negatively charged phospholipid membranes in the presence of calcium ions. The prothrombinase complex catalyzes the conversion of prothrombin , an inactive zymogen,...
), that are involved in the conversion of prothrombin to thrombin
Thrombin
Thrombin is a "trypsin-like" serine protease protein that in humans is encoded by the F2 gene. Prothrombin is proteolytically cleaved to form thrombin in the first step of the coagulation cascade, which ultimately results in the stemming of blood loss...
. In Scott syndrome, the mechanism for translocating PS to the platelet membrane is defective, resulting in impaired thrombin
Thrombin
Thrombin is a "trypsin-like" serine protease protein that in humans is encoded by the F2 gene. Prothrombin is proteolytically cleaved to form thrombin in the first step of the coagulation cascade, which ultimately results in the stemming of blood loss...
formation. A similar defect in PS translocation has also been demonstrated in Scott syndrome red blood cells and Epstein-Barr virus
Epstein-Barr virus
The Epstein–Barr virus , also called human herpesvirus 4 , is a virus of the herpes family and is one of the most common viruses in humans. It is best known as the cause of infectious mononucleosis...
transformed lymphocytes, suggesting that the defect in Scott syndrome reflects a mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
in a stem cell
Stem cell
This article is about the cell type. For the medical therapy, see Stem Cell TreatmentsStem cells are biological cells found in all multicellular organisms, that can divide and differentiate into diverse specialized cell types and can self-renew to produce more stem cells...
that effects multiple hematological lineages. The basis for the defect in PS translocation is, at present, unknown. A candidate protein, scramblase
Scramblase
Scramblase is a protein responsible for the translocation of phospholipids between the two monolayers of a lipid bilayer of a cell membrane. In humans, phospholipid scramblases constitute a family of five homologous proteins that are named as hPLSCR1–hPLSCR5. Scramblases are members of the...
, that may be involved in this process appears to be normal in Scott syndrome platelets. Other possible defects in PS translocation, reported in some patients, require further study. 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.
Further reading
- Heemskerk JWM, Bevers EM, Lindhout T. Platelet activation and blood coagulation, Thromb Haem 2002; 88:186-194
- Martinez MC, Martin S, Toti F, Fressinaud E, Dachary-Prigent J, Meyer D, et al. Significance of capacitative Ca2+ entry to the regulation of phoshatidylserine expression at the surface of stimulated cells. Biochemistry 1999; 38:10092-10098
- Munnix ICA, Harmsma M, Diddings JC, Collins PW, Feijge P, Comfurius JWM, et al. Store-mediated Ca2+ entry in the regulation of phoshatidylserine exposure in blood cells from Scott patients. Thromb Haemost 2003; 89:687-695
- Weiss HJ, Vicic WJ, Lages BA, Rogers J. Isolated deficiency of platelet procoagulant activity. Am J Med 1979; 67:206-213
- Miletich JP, Kane WH, Hofmann SL, Stanford N, Majerus PW. Deficiency of factor Xa-factor Va binding sites on the platelets of a patient with a bleeding disorder. Blood 1979; 54:1015-1022
- Bevers EM, Wiedmer T, Comfurius P, Shattil SJ, Weiss HJ, Zwaal RFA, et al. Defective Ca2+ induced microvesiculation and deficient expression of procoagulant activity in erythrocytes from a patient with a bleeding disorder: a study of the red blood cells of Scott syndrome. Blood 1992;79:380-388
- Kojima H, Newton-Nash D, Weiss HJ, Sims PJ, Zhao J, Wiedmer T. Production and characterization of transformed B-lymphocytes expressing the membrane defect of Scott Syndrome. J Clin Invest 1994; 94:2237-2244
- Stout JG, Basse F, Luhm RA, Weiss HJ, Wiedmer T, Sims PJ. Scott syndrome erythrocytes contain a membrane protein capable of mediating Ca2+-dependent transbilayer migration of membrane phospholipids. J Clin Invest 1997; 99:2232-2238
- Albrecht C, McVey JH, Elliott JI, Sardini A, Kasza I, Mumford AD, et al. A novel missense mutation in ABCA1 results in altered protein trafficking and reduced phosphatidylserine translocation in a patient with Scott syndrome. Blood 2005; 106:542-549
- Brooks MB, Catalfamo JL, Alex Brown H, Ivanova P, Lovaglio J. A hereditary bleeding disorder of dogs caused by a lack of platelet procoagulant activity. Blood 2002; 99:2434-2441