Paroxysmal nocturnal hemoglobinuria and the complement system: Recent insights and novel anticomplement strategies

Advances in Experimental Medicine and Biology

Volumn 734, Issue , 2013, Pages 155-172

  Risitano, Antonio M ^a  

^a UNIVERSITY OF NAPLES FEDERICO II   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

CD34 ANTIGEN; CD59 ANTIGEN; COMPLEMENT COMPONENT C3B; COMPLEMENT COMPONENT C3D; COMPLEMENT COMPONENT C5; COMPLEMENT FACTOR H; COMPLEMENT FACTOR I; COMPLEMENT INHIBITOR; DECAY ACCELERATING FACTOR; ECULIZUMAB; GLYCOSYLPHOSPHATIDYLINOSITOL ANCHORED PROTEIN; HYBRID PROTEIN; PHOSPHATIDYLINOSITOL; PHOSPHATIDYLINOSITOL GLYCAN CLASS A; PLACEBO; RECOMBINANT ERYTHROPOIETIN; STEROID; TT 30; UNCLASSIFIED DRUG; COMPLEMENT COMPONENT C3; COMPLEMENT COMPONENT C3 INHIBITOR;

BONE MARROW DEPRESSION; CLINICAL FEATURE; COMPLEMENT ACTIVATION; COMPLEMENT DEPOSITION; COMPLEMENT INHIBITION; COMPLEMENT SYSTEM; CONFERENCE PAPER; DISEASE CONTROL; DRUG EFFICACY; DRUG SAFETY; DRUG TARGETING; GENE; GENE EXPRESSION; GENE MUTATION; HUMAN; IMMUNE DYSREGULATION; IMMUNOMODULATION; IMMUNOPATHOGENESIS; IMMUNOREGULATION; INTRAVASCULAR HEMOLYSIS; NONHUMAN; PAROXYSMAL NOCTURNAL HEMOGLOBINURIA; PIG A GENE; PRIORITY JOURNAL; SPLENECTOMY; THROMBOCYTE ACTIVATION; THROMBOPHILIA; UNSPECIFIED SIDE EFFECT; ERYTHROCYTE; PATHOPHYSIOLOGY; RETICULOENDOTHELIAL SYSTEM;

EID: 84934437847     PISSN: 00652598     EISSN: None     Source Type: Book Series    
DOI: 10.1007/978-1-4614-4118-2_10     Document Type: Conference Paper

References (108)

1. Araten DJ, Nafa K, Pakdeesuwan K et al (1999) Clonal populations of hematopoietic cells with paroxysmal nocturnal hemoglobinuria genotype and phenotype are present in normal individuals. Proc Natl Acad Sci USA 96:5209-52144
2. Araten DJ, Bessler M, McKenzie S et al (2002) Dynamics of hematopoiesis in paroxysmal nocturnal hemoglobinuria (PNH): no evidence for intrinsic growth advantage of PNH clones. Leukemia 16:2243-22488
3. Armstrong C, Schubert J, Ueda E et al (1992) Affected paroxysmal nocturnal hemoglobinuria T lymphocytes harbor a common defect in assembly of N-acetyl-D-glucosamine inositol phospholipid corresponding to that in class A Thy-1-urine lymphoma mutants. J Biol Chem 267:25347-253511
4. Audebert HJ, Planck J, Eisenburg M et al (2005) Cerebral ischemic infarction in paroxysmal nocturnal hemoglobinuria report of 2 cases and updated review of 7 previously published patients. J Neurol 252:1379-13866
5. Brodsky RA, Young NS, Antonioli E et al (2008) Multicenter phase III study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria. Blood 114:1840-18477
6. Brodsky RA (2009) How I treat paroxysmal nocturnal hemoglobinuria. Blood 113:6522-65277
7. Chen G, Zeng W, Maciejewski JP et al (2005) Differential gene expression in hematopoietic progenitors from paroxysmal nocturnal hemoglobinuria patients reveals an apoptosis/immune response in 'normal' phenotype cells. Leukemia 19:862-8688
8. Crosby WH (1951) Paroxysmal nocturnal hemoglobinuria; a classic description by Paul Strübling in 1882, and a bibliography of the disease. Blood 63:270-2844
9. Dameshek W (1967) Riddle: what do aplastic anemia, paroxysmal nocturnal hemoglobinuria (PNH) and "hypoplastic" leukemia have in common? Blood 30:251-2544
10. de Latour RP, Mary JY, Salanoubat C et al (2008) French Association of Young Hematologists Paroxysmal nocturnal hemoglobinuria: natural history of disease subcategories. Blood 112:3099-31066
11. Dunn DE, Liu JM, Young NS (2000) Paroxysmal nocturnal hemoglobinuria. In: Young NS (ed) Bone marrow failure syndromes. W.B. Saunders Company, Philadelphia, pp 99-1211
12. Endo M, Ware RE, Vreeke TM et al (1996) Molecular basis of the heterogeneity of expression of glycosyl phosphatidylinositol anchored proteins in paroxysmal nocturnal hemoglobinuria. Blood 87:2546-25577
13. Ferreira VP, Pangburn MK (2007) Factor H mediated cell surface protection from complement is critical for the survival of PNH erythrocytes. Blood 15(110):1290-12922
14. Gargiulo L, Lastraioli S, Cerruti G et al (2007) Highly homologous T-cell receptor beta sequences support a common target for autoreactive T cells in most patients with paroxysmal nocturnal hemoglobinuria. Blood 109:5036-50422
15. Gralnick HR, Vail M, McKeown LP et al (1995) Activated platelets in paroxysmal nocturnal haemoglobinuria. Br J Haematol 91:697-7022
16. Grünewald M, Siegemund A, Grünewald A et al (2003) Plasmatic coagulation and fi brinolytic system alterations in PNH: relation to clone size. Blood Coagul Fibrinolysis 14:685-6955
17. Hall C, Richards S, Hillmen P (2003) Primary prophylaxis with warfarin prevents thrombosis in paroxysmal nocturnal hemoglobinuria (PNH). Blood 102:3587-35911
18. Ham TH, Dingle JH (1939) Studies on the destruction of red blood cells. II. Chronic hemolytic anemia with paroxysmal nocturnal hemoglobinuria: certain immunological aspects of the hemolytic mechanism with special reference to serum complement. J Clin Invest 18:657-6722
19. Helley D, de Latour RP, Porcher R et al (2010) French Society of Hematology. Evaluation of hemostasis and endothelial function in patients with paroxysmal nocturnal hemoglobinuria receiving eculizumab. Haematologica 95:574-5811
20. Hill A, Richards SJ, Rother RP et al (2007) Erythropoietin treatment during complement inhibition with eculizumab in a patient with paroxysmal nocturnal hemoglobinuria. Haematologica 92:e31, ECR144
21. Hill A, Rother RP, Arnold L et al (2010) Eculizumab prevents intravascular hemolysis in patients with paroxysmal nocturnal hemoglobinuria and unmasks low-level extravascular hemolysis occurring through C3 opsonization. Haematologica 95:567-5733
22. Hillmen P, Lewis SM, Bessler M et al (1995) Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med 333:1253-12588
23. Hillmen P, Hall C, Marsh JC et al (2004) Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria. N Engl J Med 350:552-5599
24. Hillmen P, Young NS, Schubert J et al (2006) The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med 355:1233-12433
25. Hillmen P, Muus P, Duhrsen U et al (2007) Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria. Blood 110:4123-41288
26. Hirose S, Ravi L, Prince GM et al (1992) Synthesis of mannosylglucosaminylinositol phospholipids in normal but not paroxysmal nocturnal hemoglobinuria cells. Proc Natl Acad Sci USA 89:6025-60299
27. Hoekstra J, Leebeek FW, Plessier A et al (2009) Paroxysmal nocturnal hemoglobinuria in Budd-Chiari syndrome: fi ndings from a cohort study. J Hepatol 51:696-7066
28. Holers VM (2008) The spectrum of complement alternative pathway-mediated diseases. Immunol Rev 223:300-3166
29. Holguin MH, Fredrick LR, Bernshaw NJ et al (1989a) Isolation and characterization of a membrane protein from normal human erythrocytes that inhibits reactive lysis of the erythrocytes of paroxysmal nocturnal hemoglobinuria. J Clin Invest 84:7-177
30. Holguin MH, Wilcox LA, Bernshaw NJ et al (1989b) Relationship between the membrane inhibitor of reactive lysis and the erythrocyte phenotypes of paroxysmal nocturnal hemoglobinuria. J Clin Invest 84:1387-13944
31. Holguin MH, Martin CB, Bernshaw NJ et al (1992) Analysis of the effects of activation of the alternative pathway of complement on erythrocytes with an isolated Deficiency of decay accelerating factor. J Immunol 148:498-5022
32. Hugel B, Socié G, Vu T et al (1999) Elevated levels of circulating procoagulant microparticles in patients with paroxysmal nocturnal hemoglobinuria and aplastic anemia. Blood 93:3451-34566
33. Jasinski M, Keller P, Fujiwara Y et al (2001) GATA1-Cre mediates Piga gene inactivation in the erythroid/megakaryocytic lineage and leads to circulating red cells with a partial Deficiency in glycosyl phosphatidylinositol-linked proteins (paroxysmal nocturnal hemoglobinuria type II cells). Blood 98:2248-22555
34. Karadimitris A, Manavalan JS, Thaler HT et al (2000) Abnormal T-cell repertoire is consistent with immune process underlying the pathogenesis of paroxysmal nocturnal hemoglobinuria. Blood 96:2613-26200
35. Kawagoe K, Kitamura D, Okabe M et al (1996) Glycosylphosphatidylinositol- anchor-de ficient mice: implications for clonal dominance of mutant cells in paroxysmal nocturnal hemoglobinuria. Blood 87:3600-36066
36. Keller P, Payne JL, Tremml G et al (2001) FES-Cre targets phosphatidylinositol glycan class A (PIGA) inactivation to hematopoietic stem cells in the bone marrow. J Exp Med 194:581-5899
37. Kelly RJ, Hill A, Arnold LM et al (2011) Long-term treatment with eculizumab in paroxysmal nocturnal hemoglobinuria: sustained efficacy and improved survival. Blood 117:6786-67922
38. Kinoshita T, Medof ME, Silber R et al (1985) Distribution of decay-accelerating factor in the peripheral blood of normal individuals and patients with paroxysmal nocturnal hemoglobinuria. J Exp Med 162:75-922
39. Kunstling TR, Rosse WF (1969) Erythrocyte acetylcholinesterase Deficiency in paroxysmal nocturnal hemoglobinuria (PNH). A comparison of the complement-sensitive and insensitive populations. Blood 33:607-6166
40. Lewis SM, Dacie JV (1967) The aplastic anaemia-paroxysmal nocturnal haemoglobinuria syndrome. Br J Haematol 13:236-2511
41. Lindorfer MA, Pawluczkowycz AW, Peek EM et al (2010) A novel approach to preventing the hemolysis of paroxysmal nocturnal hemoglobinuria: both complement-mediated cytolysis and C3 deposition are blocked by a monoclonal antibody specific for the alternative pathway of complement. Blood 115:2283-22911
42. Louwes H, Vellenga E, de Wolf JT (2001) Abnormal platelet adhesion on abdominal vessels in asymptomatic patients with paroxysmal nocturnal hemoglobinuria. Ann Hematol 80:573-5766
43. Luzzatto L, Notaro R (2003) Paroxysmal nocturnal hemoglobinuria. In: Handin RI, Lux SE, Stossel TP (eds) Blood, principles and practice of hematology, 2nd edn. Lippincott Williams & Wilkins, Philadelphia, pp 319-3344
44. Luzzatto L, Bessler M, Rotoli B (1997) Somatic mutations in paroxysmal nocturnal hemoglobinuria: a blessing in disguise? Cell 88:1-44
45. Luzzatto L, Risitano AM, Notaro R (2010) Paroxysmal nocturnal hemoglobinuria and eculizumab. Haematologica 95:523-5266
46. Maciejewski JP, Sloand EM, Sato T et al (1997) Impaired hematopoiesis in paroxysmal nocturnal hemoglobinuria/aplastic anemia is not associated with a selective proliferative defect in the glycosylphosphatidylinositol-anchored protein-de ficient clone. Blood 89:1173-11811
47. Mahoney JF, Urakaze M, Hall S et al (1992) Defective glycosylphosphatidylinositol anchor synthesis in paroxysmal nocturnal hemoglobinuria granulocytes. Blood 79:1400-14033
48. Markiewski MM, Nilsson B, Ekdahl KN et al (2007) Complement and coagulation: strangers or partners in crime? Trends Immunol 28:184-1922
49. Matis LA, Rollins SA (1995) Complement-specific antibodies: designing novel anti-Inflammatories. Nat Med 1:839-8422
50. Medof ME, Gottlieb A, Kinoshita T et al (1987) Relationship between decay accelerating factor Deficiency, diminished acetylcholinesterase activity, and defective terminal complement pathway restriction in paroxysmal nocturnal hemoglobinuria erythrocytes. J Clin Invest 80:165-1744
51. Meri S, Morgan BP, Davies A et al (1990) Human protectin (CD59), an 18,000-20,000 MW complement lysis restricting factor, inhibits C5b-8 catalysed insertion of C9 into lipid bilayers. Immunology 71:1-99
52. Merry AH, Rawlinson VI, Uchikawa M et al (1989) Studies on the sensitivity to complement-mediated lysis of erythrocytes (Inab phenotype) with a Deficiency of DAF (decay accelerating factor). Br J Haematol 73:248-2533
53. Miyata T, Takeda J, Iida Y et al (1993) The cloning of PIG-A, a component in the early step of GPI-anchor biosynthesis. Science 259:1318-13200
54. Mold C, Walter EI, Medof ME (1990) The in fluence of membrane components on regulation of alternative pathway activation by decay-accelerating factor. J Immunol 145:3836-38411
55. Motoyama N, Okada N, Yamashina M et al (1992) Paroxysmal nocturnal hemoglobinuria due to hereditary nucleotide deletion in the HRF20 (CD59) gene. Eur J Immunol 22:2669-26733
56. Moyo VM, Mukhina GL, Garrett ES et al (2004) Natural history of paroxysmal nocturnal haemoglobinuria using modern diagnostic assays. Br J Haematol 126:133-1388
57. Müller-Eberhard HJ (1988) Molecular organization and function of the complement system. Annu Rev Biochem 57:321-3477
58. Nicholson-Weller A (1992) Decay accelerating factor (CD55). Curr Top Microbiol Immunol 178:7-300
59. Nicholson-Weller A, Burge J, Fearon DT et al (1982) Isolation of a human erythrocyte membrane glycoprotein with decay-accelerating activity for C3 convertases of the complement system. J Immunol 129:184-1899
60. Nicholson-Weller A, March JP, Rosenfeld SI et al (1983) Affected erythrocytes of patients with paroxysmal nocturnal hemoglobinuria are de ficient in the complement regulatory protein, decay accelerating factor. Proc Natl Acad Sci USA 80:5066-50700
61. Ninomiya H, Hasegawa Y, Nagasawa T et al (1997) Excess soluble urokinase-type plasminogen activator receptor in the plasma of patients with paroxysmal nocturnal hemoglobinuria inhibits cell-associated fi brinolytic activity. Int J Hematol 65:285-2911
62. Nishimura J, Inoue N, Wada H et al (1997) A patient with paroxysmal nocturnal hemoglobinuria bearing four independent PIG-A mutant clones. Blood 89:3470-34766
63. Nishimura J Ji, Hirota T, Kanakura Y et al (2002) Long-term support of hematopoiesis by a single stem cell clone in patients with paroxysmal nocturnal hemoglobinuria. Blood 99:2748-27511
64. Nishimura J, Kanakura Y, Ware RE et al (2004) Clinical course and flow cytometric analysis of paroxysmal nocturnal hemoglobinuria in the United States and Japan. Medicine (Baltimore) 83:193-2077
65. Oni BS, Osunkoya BO, Luzzatto L (1970) Paroxysmal nocturnal hemoglobinuria: evidence for monoclonal origin of abnormal red cells. Blood 36:145-1522
66. Orphanet (2004) Paroxysmal nocturnal hemoglobinuria, 1-12-2004. Ref Type: Internet Communication
67. Pangburn MK, Müller-Eberhard HJ (1983) Initiation of the alternative complement pathway due to spontaneous hydrolysis of the thioester of C3. Ann N Y Acad Sci 421:291-2988
68. Pangburn MK, Schreiber RD, Müller-Eberhard HJ (1981) Formation of the initial C3 convertase of the alternative complement pathway. Acquisition of C3b-like activities by spontaneous hydrolysis of the putative thioester in native C3. J Exp Med 154:856-8677
69. Pangburn MK, Schreiber RD, Trombold JS et al (1983a) Paroxysmal nocturnal hemoglobinuria: Deficiency in factor H-like functions of the abnormal erythrocytes. J Exp Med 157:1971-19800
70. Pangburn MK, Schreiber RD, Müller-Eberhard HJ (1983b) Deficiency of an erythrocyte membrane protein with complement regulatory activity in paroxysmal nocturnal hemoglobinuria. Proc Natl Acad Sci USA 80:5430-54344
71. Pangburn MK, Schreiber RD, Müller-Eberhard HJ (1983c) C3b deposition during activation of the alternative complement pathway and the effect of deposition on the activating surface. J Immunol 131:1930-19355
72. Parker CJ, Ware RE (2003) Paroxysmal nocturnal hemoglobinuria. In: Greer J et al (eds) Wintrobe's clinical hematology, 11th edn. Lippincott Williams & Wilkins, Philadelphia, pp 1203-12211
73. Parker CJ, Baker PJ, Rosse WF (1982) Increased enzymatic activity of the alternative pathway convertase when bound to the erythrocytes of paroxysmal nocturnal hemoglobinuria. J Clin Invest 69:337-3466
74. Parker C, Omine M, Richards S, International PNH Interest Group et al (2005) Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood 106:3699-37099
75. Poggi A, Negrini S, Zocchi MR et al (2005) Patients with paroxysmal nocturnal hemoglobinuria have a high frequency of peripheral-blood T cells expressing activating isoforms of inhibiting superfamily receptors. Blood 106: 2399-24088
76. Ricklin D, Lambris JD (2008) Compstatin: a complement inhibitor on its way to clinical application. Adv Exp Med Biol 632:273-2922
77. Risitano AM, Maciejewski JP, Green S et al (2004) In vivo dominant immune responses in aplastic anemia patients: molecular tracking of putatively pathogenic T cells by TCR b -CDR3 sequencing. Lancet 364:353-3633
78. Risitano AM, Marando L, Seneca E et al (2008) Hemoglobin normalization after splenectomy in a paroxysmal nocturnal hemoglobinuria patient treated by eculizumab. Blood 112:449-4511
79. Risitano AM, Notaro R, Marando L et al (2009a) Complement fraction 3 binding on erythrocytes as additional mechanism of disease in paroxysmal nocturnal hemoglobinuria patients treated by eculizumab. Blood 113:4094-41000
80. Risitano AM, Holers VM, Rotoli B (2009b) TT30, a novel regulator of the complement alternative pathway (CAP), inhibits hemolysis of paroxysmal nocturnal hemoglobinuria (PNH) erythrocytes and prevents upstream C3 binding on their surface in an in vitro model. Blood 114:158a
81. Risitano AM, Notaro R, Luzzatto L et al (2010) Paroxysmal nocturnal hemoglobinuria: hemolysis before and after eculizumab. N Engl J Med 363:2270-22722
82. Risitano AM, Notaro R, Pascariello C et al (2012) The complement receptor 2/factor H fusion protein TT30 protects paroxysmal nocturnal hemoglobinuria erythrocytes from complement mediated hemolysis and C3 fragment. May 2012, [Epub ahead of print]
83. Rosse WF (1971) The life-span of complement-sensitive and -insensitive red cells in paroxysmal nocturnal hemoglobinuria. Blood 37:556-5622
84. 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. J Clin Invest 45:736-7488
85. Rother RP, Bell L, Hillmen P et al (2005) The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin: a novel mechanism of human disease. JAMA 293:1653-16622
86. Rother RP, Rollins SA, Mojcik CF et al (2007) Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Nat Biotechnol 25:1256-12644
87. Rotoli B, Luzzatto L (1989) Paroxysmal nocturnal haemoglobinuria. Baillieres Clin Haematol 2:113-1388
88. Rotoli B, Robledo R, Luzzatto L (1982) Decreased number of circulating BFU-Es in paroxysmal nocturnal hemoglobinuria. Blood 60:157-1599
89. Schafer A, Wiesmann F, Neubauer S et al (2004) Rapid regulation of platelet activation in vivo by nitric oxide. Circulation 109:1819-18222
90. Scheinberg P, Marte M, Nunez O et al (2010) Paroxysmal nocturnal hemoglobinuria clones in severe aplastic anemia patients treated with horse anti-thymocyte globulin plus cyclosporine. Haematologica 95:1075-10800
91. Selvaraj P, Rosse WF, Silber R et al (1988) The major Fc receptor in blood has a phosphatidylinositol anchor and is de ficient in paroxysmal nocturnal haemoglobinuria. Nature 333:565-5677
92. Shin ML, Hänsch G, Hu VW et al (1986) Membrane factors responsible for homologous species restriction of complement-mediated lysis: evidence for a factor other than DAF operating at the stage of C8 and C9. J Immunol 136:1777-17822
93. Sica M, Pascariello C, Rondelli T et al (2010) In vitro complement protein 5 (C5) blockade recapitulates the complement protein 3 (C3) binding to GPI-negative erythrocytes observed in paroxysmal nocturnal hemoglobinuria (PNH) patients on eculizumab. Haematologica 95(s2):196
94. Simak J, Holada K, Risitano AM et al (2004) Elevated counts of circulating endothelial membrane microparticles in paroxysmal nocturnal hemoglobinuria indicate inflammatory status and ongoing stimulation of vascular endothelium. Br J Hematol 125:804-8133
95. Sloand EM, Pfannes L, Scheinberg P et al (2008) Increased soluble urokinase plasminogen activator receptor (suPAR) is associated with thrombosis and inhibition of plasmin generation in paroxysmal nocturnal hemoglobinuria (PNH) patients. Exp Hematol 36:1616-16244
96. Socie G, Mary JY, de Gramont A et al (1996) Paroxysmal nocturnal haemoglobinuria: long-term follow-up and prognostic factors. French Society of Haematology. Lancet 348:573-5777
97. Sugimori C, Chuhjo T, Feng X et al (2006) Minor population of CD55-CD59-blood cells predicts response to immunosuppressive therapy and prognosis in patients with aplastic anemia. Blood 107:1308-13144
98. Takahashi M, Takeda J, Hirose S et al (1993) De ficient biosynthesis of N-acetylglucosaminyl-phosphatidylinositol, the first intermediate of glycosyl phosphatidylinositol anchor biosynthesis, in cell lines established from patients with paroxysmal nocturnal hemoglobinuria. J Exp Med 177:517-5211
99. Takeda J, Miyata T, Kawagoe K et al (1993) Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria. Cell 73:703-7111
100. Tremml G, Dominguez C, Rosti V et al (1999) Increased sensitivity to complement and a decreased red blood cell life span in mice mosaic for a nonfunctional Piga gene. Blood 94:2945-29544
101. van Beers EJ, Schaap MC, Berckmans RJ, CURAMA Study Group et al (2009) Circulating erythrocyte-derived microparticles are associated with coagulation activation in sickle cell disease. Haematologica 94:1513-15199
102. van der Schoot CE, Huizinga TW, van't Veer-Korthof ET et al (1990) Deficiency of glycosyl-phosphatidylinositollinked membrane glycoproteins of leukocytes in paroxysmal nocturnal hemoglobinuria, description of a new diagnostic cyto fl uorometric assay. Blood 76:1853-18599
103. Whaley K, Ruddy S (1976) Modulation of the alternative complement pathway by b 1H globulin. J Exp Med 144:1147-11633
104. Wiedmer T, Hall SE, Ortel TL et al (1993) Complement-induced vesiculation and exposure of membrane prothrombinase sites in platelets of paroxysmal nocturnal hemoglobinuria. Blood 82:1192-11966
105. Wilcox LA, Ezzell JL, Bernshaw NJ et al (1991) Molecular basis of the enhanced susceptibility of the erythrocytes of paroxysmal nocturnal hemoglobinuria to hemolysis in acidified serum. Blood 78:820-8299
106. Yamashina M, Ueda E, Kinoshita T et al (1990) Inherited complete Deficiency of 20-kilodalton homologous restriction factor (CD59) as a cause of paroxysmal nocturnal hemoglobinuria. N Engl J Med 323:1184-11899
107. Young NS, Maciejewski JP (2000) Genetic and environmental effects in paroxysmal nocturnal hemoglobinuria: this little PIG-A goes "Why? Why? Why?". J Clin Invest 106:637-6411
108. Young NS, Calado RT, Scheinberg P (2006) Current concepts in the pathophysiology and treatment of aplastic anemia. Blood 108:2509-25199