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Haemolysis in PNH: Depletion of Nitric Oxide

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Paroxysmal Nocturnal Hemoglobinuria

Abstract

The lack of complement regulation on paroxysmal nocturnal hemoglobinuria (PNH) red cells renders these cells extremely sensitive to complement-mediated lysis resulting in free haemoglobin release. Nitric oxide induces a coordinated programme of cellular events that promote blood flow and maintain smooth muscle tone. Nitric oxide reacts with haem groups quickly and irreversibly. In situations of intravascular haemolysis, as seen in PNH, nitric oxide will be rapidly depleted leading to systemic symptoms and complications. These include symptoms of smooth muscle dystonia such as abdominal pain, dysphagia and erectile dysfunction. It is also likely to contribute to significant fatigue. Complications such as thrombosis and pulmonary hypertension can also occur due to the contribution of depletion of nitric oxide.

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References

  1. Arnold WP, Mittal CK, Katsuki S, Murad F (1977) Nitric oxide activates guanylate cyclase and increases guanosine 3′:5′-cyclic monophosphate levels in various tissue preparations. Proc Natl Acad Sci U S A 74:3203–3207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Aslan M, Freeman BA (2004) Oxidant-mediated impairment of nitric oxide signaling in sickle cell disease–mechanisms and consequences. Cell Mol Biol 50:95–105

    CAS  PubMed  Google Scholar 

  3. Aslan M, Ryan TM, Adler B, Townes TM, Parks DA, Thompson JA, Tousson A, Gladwin MT, Patel RP, Tarpey MM, Batinic-Haberle I, White CR, Freeman BA (2001) Oxygen radical inhibition of nitric oxide-dependent vascular function in sickle cell disease. Proc Natl Acad Sci U S A 98:15215–15220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Aslan M, Ryan TM, Townes TM, Coward L, Kirk MC, Barnes S, Alexander CB, Rosenfeld SS, Freeman BA (2003) Nitric oxide-dependent generation of reactive species in sickle cell disease. Actin tyrosine induces defective cytoskeletal polymerization. J Biol Chem 278:4194–4204

    Article  CAS  PubMed  Google Scholar 

  5. Azizi E, Dror Y, Wallis K (1970) Arginase activity in erythrocytes of healthy and ill children. Clin Chim Acta 28:391–396

    Article  CAS  PubMed  Google Scholar 

  6. Ballard SA, Gingell CJ, Tang K, Turner LA, Price ME, Naylor AM (1998) Effects of sildenafil on the relaxation of human corpus cavernosum tissue in vitro and on the activities of cyclic nucleotide phosphodiesterase isozymes. J Urol 159:2164–2171

    Article  CAS  PubMed  Google Scholar 

  7. Baranano DE, Rao M, Ferris CD, Snyder SH (2002) Biliverdin reductase: a major physiologic cytoprotectant. Proc Natl Acad Sci U S A 99:16093–16098

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Belhassen L, Pelle G, Sediame S, Bachir D, Carville C, Bucherer C, Lacombe C, Galacteros F, Adnot S (2001) Endothelial dysfunction in patients with sickle cell disease is related to selective impairment of shear stress-mediated vasodilation. Blood 97:1584–1589

    Article  CAS  PubMed  Google Scholar 

  9. Bortolotti M, Pandolfo N, Giovannini M, Mari C, Miglioli M (2002) Effect of Sildenafil on hypertensive lower oesophageal sphincter. Eur J Clin Invest 32:682–685

    Article  CAS  PubMed  Google Scholar 

  10. Cannon RO, Schechter AN, Panza JA, Ognibene FP, Pease-Fye ME, Waclawiw MA, Shelhamer JH, Gladwin MT (2001) Effects of inhaled nitric oxide on regional blood flow are consistent with intravascular nitric oxide delivery. J Clin Invest 108:279–287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Carlsen E, Comroe JH Jr (1958) The rate of uptake of carbon monoxide and of nitric oxide by normal human erythrocytes and experimentally produced spherocytes. J Gen Physiol 42:83–107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Carmichael FJ, Ali AC, Campbell JA, Langlois SF, Biro GP, Willan AR, Pierce CH, Greenburg AG (2000) A phase I study of oxidized raffinose cross-linked human hemoglobin. Crit Care Med 28:2283–2292

    Article  CAS  PubMed  Google Scholar 

  13. Cassoly R, Gibson Q (1975) Conformation, co-operativity and ligand binding in human hemoglobin. J Mol Biol 91:301–313

    Article  CAS  PubMed  Google Scholar 

  14. Closs EI (2002) Expression, regulation and function of carrier proteins for cationic amino acids. Curr Opin Nephrol Hypertens 11:99–107

    Article  PubMed  Google Scholar 

  15. Coin JT, Olson JS (1979) The rate of oxygen uptake by human red blood cells. J Biol Chem 254:1178–1190

    CAS  PubMed  Google Scholar 

  16. Corbin JD, Francis SH, Webb DJ (2002) Phosphodiesterase type 5 as a pharmacologic target in erectile dysfunction. Urology 60:4–11

    Article  PubMed  Google Scholar 

  17. de Figueiredo LF, Mathru M, Solanki D, MacDonald VW, Hess J, Kramer GC (1997) Pulmonary hypertension and systemic vasoconstriction may offset the benefits of acellular hemoglobin blood substitutes. J Trauma 42:847–854

    Article  PubMed  Google Scholar 

  18. Deem S, Kim JU, Manjula BN, Acharya AS, Kerr ME, Patel RP, Gladwin MT, Swenson ER (2002) Effects of S-nitrosation and cross-linking of hemoglobin on hypoxic pulmonary vasoconstriction in isolated rat lungs. Circ Res 91:626–632

    Article  CAS  PubMed  Google Scholar 

  19. Dias-Da-Motta P, Arruda VR, Muscara MN, Saad ST, De NG, Costa FF, Condino-Neto A (1996) The release of nitric oxide and superoxide anion by neutrophils and mononuclear cells from patients with sickle cell anaemia. Br J Haematol 93:333–340

    Article  CAS  PubMed  Google Scholar 

  20. Eberhardt RT, McMahon L, Duffy SJ, Steinberg MH, Perrine SP, Loscalzo J, Coffman JD, Vita JA (2003) Sickle cell anemia is associated with reduced nitric oxide bioactivity in peripheral conduit and resistance vessels. Am J Hematol 74:104–111

    Article  CAS  PubMed  Google Scholar 

  21. Eherer AJ, Schwetz I, Hammer HF, Petnehazy T, Scheidl SJ, Weber K, Krejs GJ (2002) Effect of sildenafil on oesophageal motor function in healthy subjects and patients with oesophageal motor disorders. Gut 50:758–764

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Eich RF, Li T, Lemon DD, Doherty DH, Curry SR, Aitken JF, Mathews AJ, Johnson KA, Smith RD, Phillips GN Jr, Olson JS (1996) Mechanism of NO-induced oxidation of myoglobin and hemoglobin. Biochemistry 35:6976–6983

    Article  CAS  PubMed  Google Scholar 

  23. Erhart SM, Cole DJ, Patel PM, Drummond JC, Burhop KE (2000) Effect of alpha-alpha diaspirin crosslinked hemoglobin (DCLHb) on the potency of sodium nitroprusside and nitroglycerine to decrease blood pressure in rats: a dose–response study. Artif Cells Blood Substit Immobil Biotechnol 28:385–396

    Article  CAS  PubMed  Google Scholar 

  24. Farber HW, Loscalzo J (2004) Pulmonary arterial hypertension. N Engl J Med 351:1655–1665

    Article  CAS  PubMed  Google Scholar 

  25. Furchgott RF, Zawadzki JV (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288:373–376

    Article  CAS  PubMed  Google Scholar 

  26. Gladwin MT, SachdevV JML, ShizukudaY PJF, Minter K, Brown B, Coles WA, Nichols JS, Ernst I, Hunter LA, Blackwelder WC, Schechter AN, Rodgers GP, Castro O, Ognibene FP (2004) Pulmonary hypertension as a risk factor for death in patients with sickle cell disease. N Engl J Med 350:886–895

    Article  CAS  PubMed  Google Scholar 

  27. Gladwin MT, Schechter AN, Ognibene FP, Coles WA, Reiter CD, Schenke WH, Csako G, Waclawiw MA, Panza JA, Cannon RO III (2003) Divergent nitric oxide bioavailability in men and women with sickle cell disease. Circulation 107:271–278

    Article  CAS  PubMed  Google Scholar 

  28. Hartmann RC, Jenkins DE Jr, McKee LC, Heyssel RM (1966) Paroxysmal nocturnal hemoglobinuria: clinical and laboratory studies relating to iron metabolism and therapy with androgen and iron. Medicine (Baltimore) 45:331–363

    Article  CAS  Google Scholar 

  29. Hebbel RP (1985) Auto-oxidation and a membrane-associated ‘Fenton reagent’: a possible explanation for development of membrane lesions in sickle erythrocytes. Clin Haematol 14:129–140

    CAS  PubMed  Google Scholar 

  30. Hebbel RP, Osarogiagbon R, Kaul D (2004) The endothelial biology of sickle cell disease: inflammation and a chronic vasculopathy. Microcirculation 11:129–151

    Article  CAS  PubMed  Google Scholar 

  31. Herold S, Exner M, Nauser T (2001) Kinetic and mechanistic studies of the NO*-mediated oxidation of oxymyoglobin and oxyhemoglobin. Biochemistry 40:3385–3395

    Article  CAS  PubMed  Google Scholar 

  32. Hess JR, MacDonald VW, Brinkley WW (1993) Systemic and pulmonary hypertension after resuscitation with cell-free hemoglobin. J Appl Physiol 74:1769–1778

    CAS  PubMed  Google Scholar 

  33. Hill A, Kelly RJ, Hillmen P (2013) Thrombosis in paroxysmal nocturnal hemoglobinuria. Blood 121:4985–4996

    Article  CAS  PubMed  Google Scholar 

  34. Hill A, Rother RP, Hillmen P (2005) Improvement in the symptoms of smooth muscle dystonia during eculizumab therapy in paroxysmal nocturnal hemoglobinuria. Haematologica 90:ECR40

    PubMed  Google Scholar 

  35. Hill A, Rother RP, Wang X, Morris SM Jr, Quinn-Senger K, Kelly R, Richards SJ, Bessler M, Bell L, Hillmen P, Gladwin MT (2010) Effect of eculizumab on haemolysis-associated nitric oxide depletion, dyspnoea, and measures of pulmonary hypertension in patients with paroxysmal nocturnal haemoglobinuria. Br J Haematol 149:414–425

    Article  CAS  PubMed  Google Scholar 

  36. Hill A, Sapsford RJ, Scally A, Kelly R, Richards SJ, Khurisgara G, Sivananthan MU, Hillmen P (2012) Under-recognized complications in patients with paroxysmal nocturnal haemoglobinuria: raised pulmonary pressure and reduced right ventricular function. Br J Haematol 158:409–414

    Article  PubMed  Google Scholar 

  37. Hillmen P, Hall C, Marsh JC, Elebute M, Bombara MP, Petro BE, Cullen MJ, Richards SJ, Rollins SA, Mojcik CF, Rother RP (2004) Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria. N Engl J Med 350:552–559

    Article  CAS  PubMed  Google Scholar 

  38. Hirsch DP, Holloway RH, Tytgat GN, Boeckxstaens GE (1998) Involvement of nitric oxide in human transient lower esophageal sphincter relaxations and esophageal primary peristalsis. Gastroenterology 115:1374–1380

    Article  CAS  PubMed  Google Scholar 

  39. Holguin MH, Fredrick LR, Bernshaw NJ, Wilcox LA, Parker CJ (1989) 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 84:7–17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Huang KT, Han TH, Hyduke DR, Vaughn MW, Van HH, Hein TW, Zhang C, Kuo L, Liao JC (2001) Modulation of nitric oxide bioavailability by erythrocytes. Proc Natl Acad Sci U S A 98:11771–11776

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Ignarro LJ (1989) Heme-dependent activation of soluble guanylate cyclase by nitric oxide: regulation of enzyme activity by porphyrins and metalloporphyrins. Semin Hematol 26:63–76

    CAS  PubMed  Google Scholar 

  42. Ignarro LJ, Byrns RE, Buga GM, Wood KS (1987) Mechanisms of endothelium-dependent vascular smooth muscle relaxation elicited by bradykinin and VIP. Am J Physiol 253:H1074–H1082

    CAS  PubMed  Google Scholar 

  43. Ignarro LJ, Byrns RE, Buga GM, Wood KS (1987) Endothelium-derived relaxing factor from pulmonary artery and vein possesses pharmacologic and chemical properties identical to those of nitric oxide radical. Circ Res 61:866–879

    Article  CAS  PubMed  Google Scholar 

  44. Jison ML, Munson PJ, Barb JJ, Suffredini AF, Talwar S, Logun C, Raghavachari N, Beigel JH, Shelhamer JH, Danner RL, Gladwin MT (2004) Blood mononuclear cell gene expression profiles characterize the oxidant, hemolytic, and inflammatory stress of sickle cell disease. Blood 104:270–280

    Article  CAS  PubMed  Google Scholar 

  45. Kato GJ, Gladwin MT, Steinberg MH (2007) Deconstructing sickle cell disease: reappraisal of the role of hemolysis in the development of clinical subphenotypes. Blood Rev 21:37–47

    Article  PubMed  Google Scholar 

  46. Kaul DK, Hebbel RP (2000) Hypoxia/reoxygenation causes inflammatory response in transgenic sickle mice but not in normal mice. J Clin Invest 106:411–420

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Kaul DK, Liu XD, Chang HY, Nagel RL, Fabry ME (2004) Effect of fetal hemoglobin on microvascular regulation in sickle transgenic-knockout mice. J Clin Invest 114:1136–1145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Kaul DK, Liu XD, Fabry ME, Nagel RL (2000) Impaired nitric oxide-mediated vasodilation in transgenic sickle mouse. Am J Physiol Heart Circ Physiol 278:H1799–H1806

    CAS  PubMed  Google Scholar 

  49. Kristiansen M, Graversen JH, Jacobsen C, Sonne O, Hoffman HJ, Law SK, Moestrup SK (2001) Identification of the haemoglobin scavenger receptor. Nature 409:198–201

    Article  CAS  PubMed  Google Scholar 

  50. LaMuraglia GM, O’Hara PJ, Baker WH, Naslund TC, Norris EJ, Li J, Vandermeersch E (2000) The reduction of the allogenic transfusion requirement in aortic surgery with a hemoglobin-based solution. J Vasc Surg 31:299–308

    Article  CAS  PubMed  Google Scholar 

  51. Lamy ML, Daily EK, Brichant JF, Larbuisson RP, Demeyere RH, Vandermeersch EA, Lehot JJ, Parsloe MR, Berridge JC, Sinclair CJ, Baron JF, Przybelski RJ (2000) Randomized trial of diaspirin cross-linked hemoglobin solution as an alternative to blood transfusion after cardiac surgery. The DCLHb Cardiac Surgery Trial Collaborative Group. Anesthesiology 92:646–656

    Article  CAS  PubMed  Google Scholar 

  52. Langlois MR, Delanghe JR (1996) Biological and clinical significance of haptoglobin polymorphism in humans. Clin Chem 42:1589–1600

    CAS  PubMed  Google Scholar 

  53. Lee R, Neya K, Svizzero TA, Vlahakes GJ (1995) Limitations of the efficacy of hemoglobin-based oxygen-carrying solutions. J Appl Physiol 79:236–242

    CAS  PubMed  Google Scholar 

  54. Liao JC, Hein TW, Vaughn MW, Huang KT, Kuo L (1999) Intravascular flow decreases erythrocyte consumption of nitric oxide. Proc Natl Acad Sci U S A 96:8757–8761

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Liu X, Miller MJ, Joshi MS, Sadowska-Krowicka H, Clark DA, Lancaster JR Jr (1998) Diffusion-limited reaction of free nitric oxide with erythrocytes. J Biol Chem 273:18709–18713

    Article  CAS  PubMed  Google Scholar 

  56. Loscalzo J (2001) Genetic clues to the cause of primary pulmonary hypertension. N Engl J Med 345:367–371

    Article  CAS  PubMed  Google Scholar 

  57. Mack AK, Kato GJ (2006) Sickle cell disease and nitric oxide: a paradigm shift? Int J Biochem Cell Biol 38:1237–1243

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Minneci PC, Deans KJ, Zhi H, Yuen PS, Star RA, Banks SM, Schechter AN, Natanson C, Gladwin MT, Solomon SB (2005) Hemolysis-associated endothelial dysfunction mediated by accelerated NO inactivation by decompartmentalized oxyhemoglobin. J Clin Invest 115:3409–3417

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Moestrup SK, Moller HJ (2004) CD163: a regulated hemoglobin scavenger receptor with a role in the anti-inflammatory response. Ann Med 36:347–354

    Article  CAS  PubMed  Google Scholar 

  60. Moncada S, Higgs A (1993) The L-arginine-nitric oxide pathway. N Engl J Med 329:2002–2012

    Article  CAS  PubMed  Google Scholar 

  61. Moraes D, Loscalzo J (1997) Pulmonary hypertension: newer concepts in diagnosis and management. Clin Cardiol 20:676–682

    Article  CAS  PubMed  Google Scholar 

  62. Morris CR (2006) New strategies for the treatment of pulmonary hypertension in sickle cell disease: the rationale for arginine therapy. Treat Respir Med 5:31–45

    Article  CAS  PubMed  Google Scholar 

  63. Morris CR, Kato GJ, Poljakovic M, Wang X, Blackwelder WC, Sachdev V, Hazen SL, Vichinsky EP, Morris SM Jr, Gladwin MT (2005) Dysregulated arginine metabolism, hemolysis-associated pulmonary hypertension, and mortality in sickle cell disease. JAMA 294:81–90

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Morris CR, Kuypers FA, Kato GJ, Lavrisha L, Larkin S, Singer T, Vichinsky EP (2005) Hemolysis-associated pulmonary hypertension in thalassemia. Ann N Y Acad Sci 1054:481–485

    Article  PubMed  PubMed Central  Google Scholar 

  65. Morris CR, Kuypers FA, Larkin S, Vichinsky EP, Styles LA (2000) Patterns of arginine and nitric oxide in patients with sickle cell disease with vaso-occlusive crisis and acute chest syndrome. J Pediatr Hematol Oncol 22:515–520

    Article  CAS  PubMed  Google Scholar 

  66. Morris CR, Morris SM Jr, Hagar W, Van Warmerdam J, Claster S, Kepka-Lenhart D, Machado L, Kuypers FA, Vichinsky EP (2003) Arginine therapy: a new treatment for pulmonary hypertension in sickle cell disease? Am J Respir Crit Care Med 168:63–69

    Article  PubMed  Google Scholar 

  67. Morris CR, Poljakovic M, Lavrisha L, Machado L, Kuypers FA, Morris SM Jr (2004) Decreased arginine bioavailability and increased serum arginase activity in asthma. Am J Respir Crit Care Med 170:148–153

    Article  PubMed  Google Scholar 

  68. Morris CR, Singer ST, Walters MC (2006) Clinical hemoglobinopathies: iron, lungs and new blood. Curr Opin Hematol 13:407–418

    CAS  PubMed  Google Scholar 

  69. Motoyama N, Okada N, Yamashina M, Okada H (1992) Paroxysmal nocturnal hemoglobinuria due to hereditary nucleotide deletion in the HRF20 (CD59) gene. Eur J Immunol 22:2669–2673

    Article  CAS  PubMed  Google Scholar 

  70. Moyo VM, Mukhina GL, Garrett ES, Brodsky RA (2004) Natural history of paroxysmal nocturnal haemoglobinuria using modern diagnostic assays. Br J Haematol 126:133–138

    Article  CAS  PubMed  Google Scholar 

  71. Murray JA, Ledlow A, Launspach J, Evans D, Loveday M, Conklin JL (1995) The effects of recombinant human hemoglobin on esophageal motor functions in humans. Gastroenterology 109:1241–1248

    Article  CAS  PubMed  Google Scholar 

  72. Nagel RL, Gibson QH (1971) The binding of hemoglobin to haptoglobin and its relation to subunit dissociation of hemoglobin. J Biol Chem 246:69–73

    CAS  PubMed  Google Scholar 

  73. Nath KA, Shah V, Haggard JJ, Croatt AJ, Smith LA, Hebbel RP, Katusic ZS (2000) Mechanisms of vascular instability in a transgenic mouse model of sickle cell disease. Am J Physiol Regul Integr Comp Physiol 279:R1949–R1955

    CAS  PubMed  Google Scholar 

  74. Naumann HN, Diggs LW, Barreras L, Williams BJ (1971) Plasma hemoglobin and hemoglobin fractions in sickle cell crisis. Am J Clin Pathol 56:137–147

    Article  CAS  PubMed  Google Scholar 

  75. Nielsen MJ, Petersen SV, Jacobsen C, Oxvig C, Rees D, Moller HJ, Moestrup SK (2006) Haptoglobin-related protein is a high-affinity hemoglobin-binding plasma protein. Blood 108:2846–2849

    Article  CAS  PubMed  Google Scholar 

  76. Olsen SB, Tang DB, Jackson MR, Gomez ER, Ayala B, Alving BM (1996) Enhancement of platelet deposition by cross-linked hemoglobin in a rat carotid endarterectomy model. Circulation 93:327–332

    Article  CAS  PubMed  Google Scholar 

  77. Olson JS, Foley EW, Rogge C, Tsai AL, Doyle MP, Lemon DD (2004) No scavenging and the hypertensive effect of hemoglobin-based blood substitutes. Free Radic Biol Med 36:685–697

    Article  CAS  PubMed  Google Scholar 

  78. Otterbein LE, Zuckerbraun BS, Haga M, Liu F, Song R, Usheva A, Stachulak C, Bodyak N, Smith RN, Csizmadia E, Tyagi S, Akamatsu Y, Flavell RJ, Billiar TR, Tzeng E, Bach FH, Choi AM, Soares MP (2003) Carbon monoxide suppresses arteriosclerotic lesions associated with chronic graft rejection and with balloon injury. Nat Med 9:183–190

    Article  CAS  PubMed  Google Scholar 

  79. Palmer RM, Ferrige AG, Moncada S (1987) Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327:524–526

    Article  CAS  PubMed  Google Scholar 

  80. Peng HB, Spiecker M, Liao JK (1998) Inducible nitric oxide: an autoregulatory feedback inhibitor of vascular inflammation. J Immunol 161:1970–1976

    CAS  PubMed  Google Scholar 

  81. Philippidis P, Mason JC, Evans BJ, Nadra I, Taylor KM, Haskard DO, Landis RC (2004) Hemoglobin scavenger receptor CD163 mediates interleukin-10 release and heme oxygenase-1 synthesis: antiinflammatory monocyte-macrophage responses in vitro, in resolving skin blisters in vivo, and after cardiopulmonary bypass surgery. Circ Res 94:119–126

    Article  CAS  PubMed  Google Scholar 

  82. Piatti G, Allegra L, Fasano V, Gambardella C, Bisaccia M, Cappellini MD (2006) Lung function in beta-thalassemia patients: a longitudinal study. Acta Haematol 116:25–29

    Article  CAS  PubMed  Google Scholar 

  83. Prestera T, Talalay P, Alam J, Ahn YI, Lee PJ, Choi AM (1995) Parallel induction of heme oxygenase-1 and chemoprotective phase 2 enzymes by electrophiles and antioxidants: regulation by upstream antioxidant-responsive elements (ARE). Mol Med 1:827–837

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Przybelski RJ, Daily EK, Kisicki JC, Mattia-Goldberg C, Bounds MJ, Colburn WA (1996) Phase I study of the safety and pharmacologic effects of diaspirin cross-linked hemoglobin solution. Crit Care Med 24:1993–2000

    Article  CAS  PubMed  Google Scholar 

  85. Radomski MW, Palmer RM, Moncada S (1987) Endogenous nitric oxide inhibits human platelet adhesion to vascular endothelium. Lancet 2:1057–1058

    Article  CAS  PubMed  Google Scholar 

  86. Reiter CD, Gladwin MT (2003) An emerging role for nitric oxide in sickle cell disease vascular homeostasis and therapy. Curr Opin Hematol 10:99–107

    Article  CAS  PubMed  Google Scholar 

  87. Reiter CD, Wang X, Tanus-Santos JE, Hogg N, Cannon RO III, Schechter AN, Gladwin MT (2002) Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease. Nat Med 8:1383–1389

    Article  CAS  PubMed  Google Scholar 

  88. Reynolds J, Follette JH, Valentine WN (1957) The arginase activity of erythrocytes and leukocytes with particular reference to pernicious anemia and thalassemia major. J Lab Clin Med 50:78–92

    CAS  PubMed  Google Scholar 

  89. Rosse WF (2000) Paroxysmal nocturnal hemoglobinuria. In: Hoffman R (ed), Churchill Livingstone, New York, pp 331–342

    Google Scholar 

  90. Rother RP, Bell L, Hillmen P, Gladwin MT (2005) The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin: a novel mechanism of human disease. JAMA 293:1653–1662

    Article  CAS  PubMed  Google Scholar 

  91. Ryter SW, Otterbein LE, Morse D, Choi AM (2002) Heme oxygenase/carbon monoxide signaling pathways: regulation and functional significance. Mol Cell Biochem 234–235:249–263

    Article  PubMed  Google Scholar 

  92. Savitsky JP, Doczi J, Black J, Arnold JD (1978) A clinical safety trial of stroma-free hemoglobin. Clin Pharmacol Ther 23:73–80

    Article  CAS  PubMed  Google Scholar 

  93. Saxena R, Wijnhoud AD, Carton H, Hacke W, Kaste M, Przybelski RJ, Stern KN, Koudstaal PJ (1999) Controlled safety study of a hemoglobin-based oxygen carrier, DCLHb, in acute ischemic stroke. Stroke 30:993–996

    Article  CAS  PubMed  Google Scholar 

  94. Schafer A, Wiesmann F, Neubauer S, Eigenthaler M, Bauersachs J, Channon KM (2004) Rapid regulation of platelet activation in vivo by nitric oxide. Circulation 109:1819–1822

    Article  PubMed  CAS  Google Scholar 

  95. Schechter AN, Gladwin MT (2003) Hemoglobin and the paracrine and endocrine functions of nitric oxide. N Engl J Med 348:1483–1485

    Article  CAS  PubMed  Google Scholar 

  96. Schnog JJ, Jager EH, van der Dijs FP, Duits AJ, Moshage H, Muskiet FD, Muskiet FA (2004) Evidence for a metabolic shift of arginine metabolism in sickle cell disease. Ann Hematol 83:371–375

    Article  CAS  PubMed  Google Scholar 

  97. Sears DA (1970) Disposal of plasma heme in normal man and patients with intravascular hemolysis. J Clin Invest 49:5–14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Sedlak TW, Snyder SH (2004) Bilirubin benefits: cellular protection by a biliverdin reductase antioxidant cycle. Pediatrics 113:1776–1782

    Article  PubMed  Google Scholar 

  99. Semenza GL (2005) Involvement of hypoxia-inducible factor 1 in pulmonary pathophysiology. Chest 128:592S–594S

    Article  CAS  PubMed  Google Scholar 

  100. Singer ST, Kuypers FA, Styles L, Vichinsky EP, Foote D, Rosenfeld H (2006) Pulmonary hypertension in thalassemia: association with platelet activation and hypercoagulable state. Am J Hematol 81:670–675

    Article  PubMed  Google Scholar 

  101. Sloan EP, Koenigsberg M, Gens D, Cipolle M, Runge J, Mallory MN, Rodman G Jr (1999) Diaspirin cross-linked hemoglobin (DCLHb) in the treatment of severe traumatic hemorrhagic shock: a randomized controlled efficacy trial. JAMA 282:1857–1864

    Article  CAS  PubMed  Google Scholar 

  102. Tabbara IA (1992) Hemolytic anemias. Diagnosis and management. Med Clin North Am 76:649–668

    Article  CAS  PubMed  Google Scholar 

  103. Ulatowski JA, Nishikawa T, Matheson-Urbaitis B, Bucci E, Traystman RJ, Koehler RC (1996) Regional blood flow alterations after bovine fumaryl beta beta-crosslinked hemoglobin transfusion and nitric oxide synthase inhibition. Crit Care Med 24:558–565

    Article  CAS  PubMed  Google Scholar 

  104. Valla D, Dhumeaux D, Babany G, Hillon P, Rueff B, Rochant H, Benhamou JP (1987) Hepatic vein thrombosis in paroxysmal nocturnal hemoglobinuria. A spectrum from asymptomatic occlusion of hepatic venules to fatal Budd-Chiari syndrome. Gastroenterology 93:569–575

    Article  CAS  PubMed  Google Scholar 

  105. Van Lente F, Marchand A, Galen RS (1981) Diagnosis of hemolytic disease by electrophoresis of erythrocyte lactate dehydrogenase isoenzymes on cellulose acetate or Agarose. Clin Chem 27:1453–1455

    PubMed  Google Scholar 

  106. Vaughn MW, Huang KT, Kuo L, Liao JC (2000) Erythrocytes possess an intrinsic barrier to nitric oxide consumption. J Biol Chem 275:2342–2348

    Article  CAS  PubMed  Google Scholar 

  107. Vaughn MW, Kuo L, Liao JC (1998) Effective diffusion distance of nitric oxide in the microcirculation. Am J Physiol 274:H1705–H1714

    CAS  PubMed  Google Scholar 

  108. Viele MK, Weiskopf RB, Fisher D (1997) Recombinant human hemoglobin does not affect renal function in humans: analysis of safety and pharmacokinetics. Anesthesiology 86:848–858

    Article  CAS  PubMed  Google Scholar 

  109. Voetsch B, Jin RC, Loscalzo J (2004) Nitric oxide insufficiency and atherothrombosis. Histochem Cell Biol 122:353–367

    Article  CAS  PubMed  Google Scholar 

  110. Vogel WM, Dennis RC, Cassidy G, Apstein CS, Valeri CR (1986) Coronary constrictor effect of stroma-free hemoglobin solutions. Am J Physiol 251:H413–H420

    CAS  PubMed  Google Scholar 

  111. Wagener FA, Eggert A, Boerman OC, Oyen WJ, Verhofstad A, Abraham NG, Adema G, van Kooyk Y, de Witte T, Figdor CG (2001) Heme is a potent inducer of inflammation in mice and is counteracted by heme oxygenase. Blood 98:1802–1811

    Article  CAS  PubMed  Google Scholar 

  112. Wang J, Weigand L, Lu W, Sylvester JT, Semenza GL, Shimoda LA (2006) Hypoxia inducible factor 1 mediates hypoxia-induced TRPC expression and elevated intracellular Ca2+ in pulmonary arterial smooth muscle cells. Circ Res 98:1528–1537

    Article  CAS  PubMed  Google Scholar 

  113. Wink DA, Mitchell JB (1998) Chemical biology of nitric oxide: insights into regulatory, cytotoxic, and cytoprotective mechanisms of nitric oxide. Free Radic Biol Med 25:434–456

    Article  CAS  PubMed  Google Scholar 

  114. Wood KC, Hebbel RP, Granger DN (2005) Endothelial cell NADPH oxidase mediates the cerebral microvascular dysfunction in sickle cell transgenic mice. FASEB J 19:989–991

    CAS  PubMed  Google Scholar 

  115. Wu G, Morris SM Jr (1998) Arginine metabolism: nitric oxide and beyond. Biochem J 336(Pt 1):1–17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Yamashina M, Ueda E, Kinoshita T, Takami T, Ojima A, Ono H, Tanaka H, Kondo N, Orii T, Okada N (1990) Inherited complete deficiency of 20-kilodalton homologous restriction factor (CD59) as a cause of paroxysmal nocturnal hemoglobinuria. N Engl J Med 323:1184–1189

    Article  CAS  PubMed  Google Scholar 

  117. Zakynthinos E, Vassilakopoulos T, Kaltsas P, Malagari E, Daniil Z, Roussos C, Zakynthinos SG (2001) Pulmonary hypertension, interstitial lung fibrosis, and lung iron deposition in thalassaemia major. Thorax 56:737–739

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Haematology, St. James’ University Hospital, Beckett Street, Leeds, West Yorkshire, LS9 7TF, UK

    Anita Hill MBChB (Hons), Ph.D.

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  1. Anita Hill MBChB (Hons), Ph.D.
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Correspondence to Anita Hill MBChB (Hons), Ph.D. .

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Editors and Affiliations

  1. Department of Hematology and Ocology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan

    Yuzuru Kanakura

  2. Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan

    Taroh Kinoshita

  3. Dept of Hematology and Ocology, Osaka University Dept of Hematology and Ocology, Suita, Osaka, Japan

    Jun-ichi Nishimura

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Hill, A. (2017). Haemolysis in PNH: Depletion of Nitric Oxide. In: Kanakura, Y., Kinoshita, T., Nishimura, Ji. (eds) Paroxysmal Nocturnal Hemoglobinuria. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56003-6_7

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  • DOI: https://doi.org/10.1007/978-4-431-56003-6_7

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