Pulmonary complications of sickle cell disease

New England Journal of Medicine

Volumn 359, Issue 21, 2008, Pages 2254-

  Gladwin, Mark T ^a   Vichinsky, Elliott ^b  

^a UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^b CHILDREN S HOSPITAL OAKLAND   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ARGININE; BRAIN NATRIURETIC PEPTIDE; HEMOGLOBIN S; NITRIC OXIDE;

ACUTE CHEST SYNDROME; CATABOLISM; CAUSAL ATTRIBUTION; DISEASE COURSE; ECHOCARDIOGRAPHY; ENDOTHELIAL DYSFUNCTION; ENDOTHELIUM CELL; FAT EMBOLISM; HEART CATHETERIZATION; HUMAN; INTRAVASCULAR HEMOLYSIS; LUNG INFARCTION; LUNG INFECTION; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PULMONARY HYPERTENSION; REVIEW; RISK FACTOR; SICKLE CELL ANEMIA; VASCULAR DISEASE;

EID: 56749163948     PISSN: 00284793     EISSN: 15334406     Source Type: Journal    
DOI: 10.1056/NEJMra0804411     Document Type: Review

References (119)

1. Platt OS. The acute chest syndrome of sickle cell disease. N Engl J Med 2000; 342:1904-7. [Erratum, N Engl J Med 2000; 343:591.]
2. Bunn HF. Pathogenesis and treatment of sickle cell disease. N Engl J Med 1997;337:762-9.
3. Steinberg MH. Management of sickle cell disease. N Engl J Med 1999;340:1021-30.
4. Aliyu ZY, Gordeuk V, Sachdev V, et al. Prevalence and risk factors for pulmonary artery systolic hypertension among sickle cell disease patients in Nigeria. Am J Hematol 2008;83:485-90.
5. Noguchi CT, Schechter AN, Rodgers GP. Sickle cell disease pathophysiology. Baillieres Clin Haematol 1993;6:57-91.
6. Brittenham GM, Schechter AN, Noguchi CT. Hemoglobin S polymerization: primary determinant of the hemolytic and clinical severity of the sickling syndromes. Blood 1985;65:183-9.
7. Noguchi CT, Rodgers GP, Serjeant G, Schechter AN. Levels of fetal hemoglobin necessary for treatment of sickle cell disease. N Engl J Med 1988;318:96-9.
8. Platt OS, Brambilla DJ, Rosse WF, et al. Mortality in sickle cell disease: life expectancy and risk factors for early death. N Engl J Med 1994;330:1639-44.
9. Vichinsky EP, Neumayr LD, Earles AN, et al. Causes and outcomes of the acute chest syndrome in sickle cell disease. N Engl J Med 2000;342:1855-65. [Erratum, N Engl J Med 2000;343:824.]
10. Pegelow CH, Colangelo L, Steinberg M, et al. Natural history of blood pressure in sickle cell disease: risks for stroke and death associated with relative hypertension in sickle cell anemia. Am J Med 1997;102:171-7.
11. Ohene-Frempong K, Weiner SJ, Sleeper LA, et al. Cerebrovascular accidents in sickle cell disease: rates and risk factors. Blood 1998;91:288-94.
12. Gladwin MT, Sachdev V, Jison ML, et al. Pulmonary hypertension as a risk factor for death in patients with sickle cell disease. N Engl J Med 2004;350:886-95.
13. Gladwin MT, Schechter AN, Ognibene FP, et al. Divergent nitric oxide bioavailability in men and women with sickle cell disease. Circulation 2003;107:271-8.
14. Eberhardt RT, McMahon L, Duffy SJ, et al. Sickle cell anemia is associated with reduced nitric oxide bioactivity in peripheral conduit and resistance vessels. Am J Hematol 2003;74:104-11.
15. Haque AK, Gokhale S, Rampy BA, Adegboyega P, Duarte A, Saldana MJ. Pulmonary hypertension in sickle cell hemoglobinopathy: a clinicopathologic study of 20 cases. Hum Pathol 2002;33:1037-43.
16. Kato GJ, Hsieh M, Machado R, et al. Cerebrovascular disease associated with sickle cell pulmonary hypertension. Am J Hematol 2006;81:503-10.
17. Kato GJ, Gladwin MT, Steinberg MH. Deconstructing sickle cell disease: reappraisal of the role of hemolysis in the development of clinical subphenotypes. Blood Rev 2007;21:37-47.
18. Perronne V, Roberts-Harewood M, Bachir D, et al. Patterns of mortality in sickle cell disease in adults in France and England. Hematol J 2002;3:56-60.
19. Kato GJ, McGowan V, Machado RF, et al. Lactate dehydrogenase as a biomarker of hemolysis-associated nitric oxide resistance, priapism, leg ulceration, pulmonary hypertension, and death in patients with sickle cell disease. Blood 2006;107:2279-85.
20. Nolan VG, Adewoye A, Baldwin C, et al. Sickle cell leg ulcers: associations with haemolysis and SNPs in Klotho, TEK and genes of the TGF-beta/BMP pathway. Br J Haematol 2006;133:570-8.
21. Nolan VG, Baldwin C, Ma Q, et al. Association of single nucleotide polymorphisms in klotho with priapism in sickle cell anaemia. Br J Haematol 2005;128:266-72.
22. Nolan VG, Wyszynski DF, Farrer LA, Steinberg MH. Hemolysis-associated priapism in sickle cell disease. Blood 2005;106:3264-7.
23. Kato GJ, Onyekwere OC, Gladwin MT. Pulmonary hypertension in sickle cell disease: relevance to children. Pediatr Hematol Oncol 2007;24:159-70.
24. Aessopos A, Farmakis D, Karagiorga M, et al. Cardiac involvement in thalassemia intermedia: a multicenter study. Blood 2001;97:3411-6.
25. Du ZD, Roguin N, Milgram E, Saab K, Koren A. Pulmonary hypertension in patients with thalassemia major. Am Heart J 1997;134:532-7.
26. Aessopos A, Stamatelos G, Skoumas V, Vassilopoulos G, Mantzourani M, Loukopoulos D. Pulmonary hypertension and right heart failure in patients with beta-thalassemia intermedia. Chest 1995;107:50-3.
27. Derchi G, Fonti A, Forni GL, et al. Pulmonary hypertension in patients with thalassemia major. Am Heart J 1999;138:384.
28. Morris CR, Kuypers FA, Kato GJ, et al. Hemolysis-associated pulmonary hypertension in thalassemia. Ann N Y Acad Sci 2005;1054:481-5.
29. Burnett AL, Bivalacqua TJ. Glucose-6-phosphate dehydrogenase deficiency: an etiology for idiopathic priapism? J Sex Med 2008;5:237-40.
30. Prabhakaran K, Jacobs BL, Smaldone MC, Franks ME. Stuttering priapism associated with hereditary spherocytosis. Can J Urol 2007;14:3702-4.
31. Thuret I, Bardakdjian J, Badens C, et al. Priapism following splenectomy in an unstable hemoglobin: hemoglobin Olmsted beta 141 (H19) Leu→Arg. Am J Hematol 1996;51:133-6.
32. Mohamed N, Jackson N. Severe thalassaemia intermedia: clinical problems in the absence of hypertransfusion. Blood Rev 1998;12:163-70.
33. Taher A, Isma'eel H, Cappellini MD. Thalassemia intermedia: revisited. Blood Cells Mol Dis 2006;37:12-20.
34. Vanscheidt W, Leder O, Vanscheidt E, et al. Leg ulcers in a patient with spherocytosis: a clinicopathological report. Dermatologica 1990;181:56-9.
35. Frenette PS. Sickle cell vaso-occlusion: multistep and multicellular paradigm. Curr Opin Hematol 2002;9:101-6.
36. Turhan A, Weiss LA, Mohandas N, Coller BS, Frenette PS. Primary role for adherent leukocytes in sickle cell vascular occlusion: a new paradigm. Proc Natl Acad Sci U S A 2002;99:3047-51.
37. Belcher JD, Bryant CJ, Nguyen J, et al. Transgenic sickle mice have vascular inflammation. Blood 2003;101:3953-9.
38. Belcher JD, Marker PH, Weber JP, Hebbel RP, Vercellotti GM. Activated monocytes in sickle cell disease: potential role in the activation of vascular endothelium and vaso-occlusion. Blood 2000;96:2451-9.
39. Osarogiagbon UR, Choong S, Belcher JD, Vercellotti GM, Paller MS, Hebbel RP. Reperfusion injury pathophysiology in sickle transgenic mice. Blood 2000;96:314-20.
40. Aslan M, Ryan TM, Adler B, et al. Oxygen radical inhibition of nitric oxide-dependent vascular function in sickle cell disease. Proc Natl Acad Sci U S A 2001;98:15215-20.
41. Wood KC, Hebbel RP, Granger DN. Endothelial cell NADPH oxidase mediates the cerebral microvascular dysfunction in sickle cell transgenic mice. FASEB J 2005;19:989-91.
42. Hsu LL, Champion HC, Campbell-Lee SA, et al. Hemolysis in sickle cell mice causes pulmonary hypertension due to global impairment in nitric oxide bioavailability. Blood 2007;109:3088-98. [Erratum, Blood 2008;111:1772.]
43. Kaul DK, Hebbel RP. Hypoxia/reoxygenation causes inflammatory response in transgenic sickle mice but not in normal mice. J Clin Invest 2000;106:411-20. [Erratum, J Clin Invest 2000;106:715.]
44. Belcher JD, Mahaseth H, Welch TE, et al. Critical role of endothelial cell activation in hypoxia-induced vasoocclusion in transgenic sickle mice. Am J Physiol Heart Circ Physiol 2005;288:H2715-H2725.
45. Platt OS. Sickle cell anemia as an inflammatory disease. J Clin Invest 2000;106:337-8.
46. Hiruma H, Noguchi CT, Uyesaka N, Schechter AN, Rodgers GP. Contributions of sickle hemoglobin polymer and sickle cell membranes to impaired filterability. Am J Physiol 1995;268:H2003-H2008.
47. Holtzclaw JD, Jack D, Aguayo SM, Eckman JR, Roman J, Hsu LL. Enhanced pulmonary and systemic response to endotoxin in transgenic sickle mice. Am J Respir Crit Care Med 2004;169:687-95.
48. Sabaa N, de Franceschi L, Bonnin P, et al. Endothelin receptor antagonism prevents hypoxia-induced mortality and morbidity in a mouse model of sickle-cell disease. J Clin Invest 2008;118:1924-33.
49. Case Records of the Massachusetts General Hospital (Case 34-1997). N Engl J Med 1997;337:1293-301.
50. Case Records of the Massachusetts General Hospital (Case 52-1983). N Engl J Med 1983;309:1627-36.
51. Gladwin MT, Rodgers GP. Pathogenesis and treatment of acute chest syndrome of sickle-cell anaemia. Lancet 2000;355:1476-8.
52. Styles LA, Schalkwijk CG, Aarsman AJ, Vichinsky EP, Lubin BH, Kuypers FA. Phospholipase A2 levels in acute chest syndrome of sickle cell disease. Blood 1996;87:2573-8.
53. Lechapt E, Habibi A, Bachir D, et al. Induced sputum versus bronchoalveolar lavage during acute chest syndrome in sickle cell disease. Am J Respir Crit Care Med 2003;168:1373-7.
54. Vichinsky E, Williams R, Das M, et al. Pulmonary fat embolism: a distinct cause of severe acute chest syndrome in sickle cell anemia. Blood 1994;83:3107-12.
55. Castro O. Systemic fat embolism and pulmonary hypertension in sickle cell disease. Hematol Oncol Clin North Am 1996;10:1289-303.
56. Bellet PS, Kalinyak KA, Shukla R, Gelfand MJ, Rucknagel DL. Incentive spirometry to prevent acute pulmonary complications in sickle cell diseases. N Engl J Med 1995;333:699-703.
57. Bryant R. Asthma in the pediatric sickle cell patient with acute chest syndrome. J Pediatr Health Care 2005;19:157-62.
58. Boyd JH, Macklin EA, Strunk RC, De-Baun MR. Asthma is associated with acute chest syndrome and pain in children with sickle cell anemia. Blood 2006;108:2923-7.
59. Knight-Madden JM, Forrester TS, Lewis NA, Greenough A. Asthma in children with sickle cell disease and its association with acute chest syndrome. Thorax 2005;60:206-10.
60. Nordness ME, Lynn J, Zacharisen MC, Scott PJ, Kelly KJ. Asthma is a risk factor for acute chest syndrome and cerebral vascular accidents in children with sickle cell disease. Clin Mol Allergy 2005;3:2.
61. Sylvester KP, Patey RA, Broughton S, et al. Temporal relationship of asthma to acute chest syndrome in sickle cell disease. Pediatr Pulmonol 2007;42:103-6.
62. Field JJ, Glassberg J, Gilmore A, et al. Longitudinal analysis of pulmonary function in adults with sickle cell disease. Am J Hematol 2008;83:574-6.
63. Klings ES, Wyszynski DF, Nolan VG, Steinberg MH. Abnormal pulmonary function in adults with sickle cell anemia. Am J Respir Crit Care Med 2006;173:1264-9.
64. Anthi A, Machado RF, Jison ML, et al. Hemodynamic and functional assessment of patients with sickle cell disease and pulmonary hypertension. Am J Respir Crit Care Med 2007;175:1272-9.
65. Rother RP, Bell L, Hillmen P, Gladwin MT. The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin: a novel mechanism of human disease. JAMA 2005;293:1653-62.
66. Nagel RL, Gibson QH. The binding of hemoglobin to haptoglobin and its relation to subunit dissociation of hemoglobin. J Biol Chem 1971;246:69-73.
67. Kristiansen M, Graversen JH, Jacobsen C, et al. Identification of the haemoglobin scavenger receptor. Nature 2001;409:198-201.
68. Ryter SW, Otterbein LE, Morse D, Choi AM. Heme oxygenase/carbon monoxide signaling pathways: regulation and functional significance. Mol Cell Biochem 2002;234-235:249-63.
69. Baranano DE, Rao M, Ferris CD, Snyder SH. Biliverdin reductase: a major physiologic cytoprotectant. Proc Natl Acad Sci U S A 2002;99:16093-8.
70. Otterbein LE, Bach FH, Alam J, et al. Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Nat Med 2000;6:422-8.
71. Melamed-Frank M, Lache O, Enav BI, et al. Structure-function analysis of the antioxidant properties of haptoglobin. Blood 2001;98:3693-8.
72. Belcher JD, Mahaseth H, Welch TE, Otterbein LE, Hebbel RP, Vercellotti GM. Heme oxygenase-1 is a modulator of inflammation and vaso-occlusion in transgenic sickle mice. J Clin Invest 2006;116:808-16.
73. Bensinger TA, Gillette PN. Hemolysis in sickle cell disease. Arch Intern Med 1974;133:624-31.
74. Reiter CD, Wang X, Tanus-Santos JE, et al. Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease. Nat Med 2002;8:1383-9.
75. Hebbel RP. Auto-oxidation and a membrane-associated 'Fenton reagent': a possible explanation for development of membrane lesions in sickle erythrocytes. Clin Haematol 1985;14:129-40.
76. Repka T, Hebbel RP. Hydroxyl radical formation by sickle erythrocyte membranes: role of pathologic iron deposits and cytoplasmic reducing agents. Blood 1991;78:2753-8.
77. Reiter CD, Gladwin MT. An emerging role for nitric oxide in sickle cell disease vascular homeostasis and therapy. Curr Opin Hematol 2003;10:99-107.
78. Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 1980;288:373-6.
79. Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci U S A 1987;84:9265-9.
80. Palmer RM, Ashton DS, Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature 1988;333:664-6.
81. Panza JA, Casino PR, Kilcoyne CM, Quyyumi AA. Role of endothelium-derived nitric oxide in the abnormal endothelium-dependent vascular relaxation of patients with essential hypertension. Circulation 1993;87:1468-74.
82. De Caterina R, Libby P, Peng HB, et al. Nitric oxide decreases cytokine-induced endothelial activation: nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines. J Clin Invest 1995;96:60-8.
83. Doherty DH, Doyle MP, Curry SR, et al. Rate of reaction with nitric oxide determines the hypertensive effect of cell-free hemoglobin. Nat Biotechnol 1998;16:672-6.
84. Butler AR, Megson IL, Wright PG. Diffusion of nitric oxide and scavenging by blood in the vasculature. Biochim Biophys Acta 1998;1425:168-76.
85. Liu X, Miller MJ, Joshi MS, Sadowska-Krowicka H, Clark DA, Lancaster JR Jr. Diffusion-limited reaction of free nitric oxide with erythrocytes. J Biol Chem 1998;273:18709-13.
86. Schechter AN, Gladwin MT. Hemoglobin and the paracrine and endocrine functions of nitric oxide. N Engl J Med 2003;348:1483-5.
87. Yu B, Raher MJ, Volpato GP, Bloch KD, Ichinose F, Zapol WM. Inhaled nitric oxide enables artificial blood transfusion without hypertension. Circulation 2008;117:1982-90.
88. Minneci PC, Deans KJ, Zhi H, et al. Hemolysis-associated endothelial dysfunction mediated by accelerated NO inactivation by decompartmentalized oxyhemoglobin. J Clin Invest 2005;115:3409-17.
89. Gladwin MT. Deconstructing endothelial dysfunction: soluble guanylyl cyclase oxidation and the NO resistance syndrome. J Clin Invest 2006;116:2330-2.
90. Nath KA, Shah V, Haggard JJ, et al. Mechanisms of vascular instability in a transgenic mouse model of sickle cell disease. Am J Physiol Regul Integr Comp Physiol 2000;279:R1949-R1955.
91. Kaul DK, Liu XD, Chang HY, Nagel RL, Fabry ME. Effect of fetal hemoglobin on microvascular regulation in sickle transgenic-knockout mice. J Clin Invest 2004;114:1136-45.
92. Kaul DK, Liu XD, Fabry ME, Nagel RL. Impaired nitric oxide-mediated vasodilation in transgenic sickle mouse. Am J Physiol Heart Circ Physiol 2000;278:H1799-H1806.
93. Morris CR, Kato GJ, Poljakovic M, et al. Dysregulated arginine metabolism, hemolysis-associated pulmonary hypertension, and mortality in sickle cell disease. JAMA 2005;294:81-90.
94. Gramaglia I, Sobolewski P, Meays D, et al. Low nitric oxide bioavailability contributes to the genesis of experimental cerebral malaria. Nat Med 2006;12:1417-22.
95. Yeo TW, Lampah DA, Gitawati R, et al. Impaired nitric oxide bioavailability and L-arginine reversible endothelial dysfunction in adults with falciparum malaria. J Exp Med 2007;204:2693-704.
96. Villagra J, Shiva S, Hunter LA, Machado RF, Gladwin MT, Kato GJ. Platelet activation in patients with sickle disease, hemolysis-associated pulmonary hypertension, and nitric oxide scavenging by cellfree hemoglobin. Blood 2007;110:2166-72.
97. Raghavachari N, Xu X, Harris A, et al. Amplified expression profiling of platelet transcriptome reveals changes in arginine metabolic pathways in patients with sickle cell disease. Circulation 2007;115:1551-62.
98. Ataga KI, Moore CG, Hillery CA, et al. Coagulation activation and inflammation in sickle cell disease-associated pulmonary hypertension. Haematologica 2008;93:20-6.
99. van Beers EJ, Spronk HM, Ten Cate H, et al. No association of the hypercoagulable state with sickle cell disease related pulmonary hypertension. Haematologica 2008;93(5):e42-e44.
100. Westerman M, Pizzey A, Hirschman J, et al. Microvesicles in haemoglobinopathies offer insights into mechanisms of hypercoagulability, haemolysis and the effects of therapy. Br J Haematol 2008;142:126-35.
101. Setty BN, Rao AK, Stuart MJ. Thrombophilia in sickle cell disease: the red cell connection. Blood 2001;98:3228-33.
102. Frei AC, Guo Y, Jones DW, et al. Vascular dysfunction in a murine model of severe hemolysis. Blood 2008;112:398-405.
103. De Castro LM, Jonassaint JC, Graham FL, Ashley-Koch A, Telen MJ. Pulmonary hypertension associated with sickle cell disease: clinical and laboratory end-points and disease outcomes. Am J Hematol 2008;83:19-25.
104. Ataga KI, Moore CG, Jones S, et al. Pulmonary hypertension in patients with sickle cell disease: a longitudinal study. Br J Haematol 2006;134:109-15.
105. Ambrusko SJ, Gunawardena S, Sakara A, et al. Elevation of tricuspid regurgitant jet velocity, a marker for pulmonary hypertension in children with sickle cell disease. Pediatr Blood Cancer 2006;47:907-13.
106. Liem RI, Young LT, Thompson AA. Tricuspid regurgitant jet velocity is associated with hemolysis in children and young adults with sickle cell disease evaluated for pulmonary hypertension. Haematologica 2007;92:1549-52.
107. Pashankar FD, Carbonella J, Bazzy-Asaad A, Friedman A. Prevalence and risk factors of elevated pulmonary artery pressures in children with sickle cell disease. Pediatrics 2008;121:777-82.
108. Onyekwere OC, Campbell A, Teshome M, et al. Pulmonary hypertension in children and adolescents with sickle cell disease. Pediatr Cardiol 2008;29:309-12.
109. Machado RF, Gladwin MT. Chronic sickle cell lung disease: new insights into the diagnosis, pathogenesis and treatment of pulmonary hypertension. Br J Haematol 2005;129:449-64.
110. Castro OL, Hoque M, Brown BD. Pulmonary hypertension in sickle cell disease: cardiac catheterization results and survival. Blood 2003;101:1257-61.
111. Ataga KI, Sood N, De Gent G, et al. Pulmonary hypertension in sickle cell disease. Am J Med 2004;117:665-9.
112. Machado RF, Anthi A, Steinberg MH, et al. N-terminal pro-brain natriuretic peptide levels and risk of death in sickle cell disease. JAMA 2006;296:310-8.
113. McQuillan BM, Picard MH, Leavitt M, Weyman AE. Clinical correlates and reference intervals for pulmonary artery systolic pressure among echocardiographically normal subjects. Circulation 2001;104:2797-802.
114. Machado RF, Kyle Mack A, Martyr S, et al. Severity of pulmonary hypertension during vaso-occlusive pain crisis and exercise in patients with sickle cell disease. Br J Haematol 2007;136:319-25.
115. Mekontso Dessap A, Leon R, Habibi A, et al. Pulmonary hypertension and cor pulmonale during severe acute chest syndrome in sickle cell disease. Am J Respir Crit Care Med 2008;177:646-53.
116. Sachdev V, Machado RF, Shizukuda Y, et al. Diastolic dysfunction is an independent risk factor for death in patients with sickle cell disease. J Am Coll Cardiol 2007;49:472-9.
117. Hayag-Barin JE, Smith RE, Tucker FC Jr. Hereditary spherocytosis, thrombocytosis, and chronic pulmonary emboli: a case report and review of the literature. Am J Hematol 1998;57:82-4.
118. Vichinsky EP. Pulmonary hypertension in sickle cell disease. N Engl J Med 2004;350:857-9.
119. Taylor JG IV, Nolan VG, Mendelsohn L, Kato GJ, Gladwin MT, Steinberg MH. Chronic hyper-hemolysis in sickle cell anemia: association of vascular complications and mortality with less frequent vasoocclusive pain. PLoS One 2008;3(5):e2095.