A new approach to controlling haemolysis

One of the most frustrating aspects of the management of PNH has been, until now, the absence of an effective way to control haemolysis. Eculizumab, a humanized antibody against complement protein C5 that inhibits the activation of terminal components of complement, has been tested in a small group of transfusion-dependent PNH patients. The results thus far appear very promising; indeed, reduced intravascular haemolysis and less haemoglobinuria have been documented, as well as a marked decrease in transfusion requirement in most patients.

Araten D, Nafa K, Pakdeesuwan K etal. (1999) Clonal populations ofhematopoietic cells with paroxysmal nocturnal hemoglobinuria genotype and phenotype are present in normal individuals. Proceedings of the National Academy of Sciences of the USA 96: 5209-14.

Bessler M, Mason PJ, Hillmen P et al. (1994) Paroxysmal nocturnal haemoglobinuria (PNH) is caused by somatic mutations in the PIG-A gene. EMBO Journal 13:110-17.

Bessler M, Schaefer A, Keller P (2001) Paroxysmal nocturnal hemoglobinuria: insights from recent advances in molecular biology. Transfusion Medicine Review 15:255-67.

Ham TH (1937) Chronic hemolytic anemia with paroxysmal nocturnal hemoglobinuria. A study of the mechanism of hemolysis in relation to acid-base equilibrium. New England Journal of Medicine217: 915-18.

Hillmen P, Lewis SM, Bessler M etal. (1995) Natural history of paryxysmal nocturnal hemoglobinuria. New England Journal of Medicine 333:1253-8.

Hillmen P, Hall C, Marsh JC et al. (2004) Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria. New England Journal of Medicine 350: 552-9.

Karadimitris A, Manavalan JS, Thaler HT et al. (2000) Abnormal T-cell repertoire is consistent with immune process underlying the pathogenesis ofparoxysmal nocturnal hemoglobinuria. Blood 96: 2613-20.

Karadimitris A, Luzzatto L (2001) The cellular pathogenesis of paroxysmal nocturnal haemoglobinuria. Leukemia 15:1148-52.

Lewis SM, Dacie JV (1967) The aplastic anaemia-paroxysmal nocturnal haemoglobinuria syndrome. British Journal of Haemato-logy 13:236-51.

Luzzatto L, Bessler M (1996) The dual pathogenesis of paroxysmal nocturnal hemoglobinuria. Current Opinion in Hematology 3: 101-10.

Luzzatto L, Notaro R (2003) Paroxysmal nocturnal hemoglobinuria. In: Blood: PrinciplesandPractice of Hematology (RI Handlin, SE Lux, TP Stossel, eds), 2nd edn, pp. 319-34. Lippincott Williams & Wilkins, Philadelphia.

Miyata T, Takeda J, Iida J etal. (1993) The cloning of PIG-A, a component in the early step of GPI-anchor biosynthesis. Science 259:1318-20.

Omine M, Kinoshita T (ed.) (2003) Paroxysmal Nocturnal Hemoglobinuria and Related Disorders - Molecular Aspects and Pathogenesis, p. 285. Springer-Verlag, Tokyo.

Oni SB, Osunkoya BO, Luzzatto L (1970) Paroxysmal nocturnal hemoglobinuria: evidence for monoclonal origin of abnormal red cells. Blood 36:145-52.

Raiola AM, Van Lint MT, Lamparelli T et al. (2000) Bone marrow transplantation for paroxysmal nocturnal hemoglobinuria. Haema-tologica 85(1): 59-62.

Rosse WF (1986) The control of complement activation by the blood cells in paroxysmal nocturnal haemoglobinuria. Blood 67: 268-9.

Rosse WF, Dacie JV (1966) Immune lysis of normal human and paroxysmal nocturnal hemoglobinuria (PNH) red blood cells. I The sensitivity of PNH red cells to lysis by complement and specific antibody. Journal of Clinical Investigation 45: 736-48.

Rotoli B, Luzzatto L (1989) Paroxysmal nocturnal hemoglobinuria. Seminars in Hematology 26:201-7.

Shichishima T, Saitoh Y, Terasawa T etal. (1999) Complement sensitivity of erythrocytes in a patient with inherited complete deficiency of CD59 or with the Inab phenotype. British Journal of Haematology 104: 303-6.

Watanabe R, Inoue N, Westfall B et al. (1998) The first step of glyco-sylphosphatidylinositol biosynthesis is mediated by a complex of PIG-A, PIG-H, PIG-C and GPI1. EMBO Journal 17:877-85.

Wiedmer T, Hall SE, Ortel TL etal. (1993) Complement-induced vesiculation and exposure of membrane prothrombinase sites in platelets of paroxysmal nocturnal hemoglobinuria. Blood 82: 1192-6.

Young NS, Moss, J (ed.) (2000) Paroxysmal Nocturnal Hemoglobinuria and the GPI-linked Proteins, p. 279. Academic Press, New York.

Zoumbos NC, Gascon P, Djeu JY et al. (1985) Circulating activated suppressor T lymphocytes in aplastic anemia. New England Journal of Medicine 312:257-65.

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