Sickle cell disease as a vascular disorder

References

• Ware RE, de Montalembert M, Tshilolo L, et al. Sickle cell disease. Lancet. 2017;390(10091):311–323.
   PubMed Web of Science ®Google Scholar
• Turhan A, Weiss LA, Mohandas N, et al. Primary role for adherent leukocytes in sickle cell vascular occlusion: a new paradigm. Proc Natl Acad Sci U S A. 2002;99(5):3047–3051.
   PubMed Web of Science ®Google Scholar
• Rees DC, Williams TN, Gladwin MT. Sickle-cell disease. Lancet. 2010;376(9757):2018–2031.
   PubMed Web of Science ®Google Scholar
• Habara A, Steinberg MH. Genetic basis of heterogeneity and severity in sickle cell disease. Exp Biol Med (Maywood). 2016;241(7):689–696.
   PubMed Web of Science ®Google Scholar
• Zhang D, Xu C, Manwani D, et al. Neutrophils, platelets, and inflammatory pathways at the nexus of sickle cell disease pathophysiology. Blood. 2016;127(7):801–809.
   PubMed Web of Science ®Google Scholar
• Morris CR. Mechanisms of vasculopathy in sickle cell disease and thalassemia. Hematology Am Soc Hematol Educ Program. 2008;2008(1):177–185.
   Google Scholar
• 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(1):37–47.
   PubMed Web of Science ®Google Scholar
• 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(6):2279–2285.
   PubMed Web of Science ®Google Scholar
• Morris CR, Kato GJ, Poljakovic M, et al. Dysregulated arginine metabolism, hemolysis-associated pulmonary hypertension, and mortality in sickle cell disease. JAMA. 2005;294(1):81–90.
   PubMed Web of Science ®Google Scholar
• Kato GJ, Martyr S, Blackwelder WC, et al. Levels of soluble endothelium-derived adhesion molecules in patients with sickle cell disease are associated with pulmonary hypertension, organ dysfunction, and mortality. Br J Haematol. 2005;130(6):943–953.
   PubMed Web of Science ®Google Scholar
• Kato GJ, Steinberg MH, Gladwin MT. Intravascular hemolysis and the pathophysiology of sickle cell disease. J Clin Invest. 2017;127(3):750–760.
   PubMed Web of Science ®Google Scholar
• Colombatti R, De Bon E, Bertomoro A, et al. Coagulation activation in children with sickle cell disease is associated with cerebral small vessel vasculopathy. PLoS One. 2013;8(10):e78801.
   PubMed Web of Science ®Google Scholar
• 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(26):15215–15220.
   PubMed Web of Science ®Google Scholar
• Reiter CD, Wang X, Tanus-Santos JE, et al. Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease. Nat Med. 2002;8(12):1383–1389.
   PubMed Web of Science ®Google Scholar
• Taylor JG, Nolan VG, Mendelsohn L, et al. Chronic hyper-hemolysis in sickle cell anemia: association of vascular complications and mortality with less frequent vasoocclusive pain. PLoS One. 2008;3(5):e2095.
   PubMed Web of Science ®Google Scholar
• Nath KA, Katusic ZS. Vasculature and kidney complications in sickle cell disease. J Am Soc Nephrol. 2012;23(5):781–784.
   PubMed Web of Science ®Google Scholar
• Nolan VG, Wyszynski DF, Farrer LA, et al. Hemolysis-associated priapism in sickle cell disease. Blood. 2005;106(9):3264–3267.
   PubMed Web of Science ®Google Scholar
• Connes P, Lamarre Y, Hardy-Dessources MD, et al. Decreased hematocrit-to-viscosity ratio and increased lactate dehydrogenase level in patients with sickle cell anemia and recurrent leg ulcers. PLoS One. 2013;8(11):e79680.
   PubMed Web of Science ®Google Scholar
• Cita KC, Brureau L, Lemonne N, et al. Men with sickle cell anemia and priapism exhibit increased hemolytic rate, decreased red blood cell deformability and increased red blood cell aggregate strength. PLoS One. 2016;11(5):e0154866.
   PubMed Web of Science ®Google Scholar
• Haymann JP, Stankovic K, Levy P, et al. Glomerular hyperfiltration in adult sickle cell anemia: a frequent hemolysis associated feature. Clin J Am Soc Nephrol. 2010;5(5):756–761.
   PubMed Web of Science ®Google Scholar
• Bunn HF, Nathan DG, Dover GJ, et al. Pulmonary hypertension and nitric oxide depletion in sickle cell disease. Blood. 2010;116(5):687–692.
   PubMed Web of Science ®Google Scholar
• Parent F, Bachir D, Inamo J, et al. A hemodynamic study of pulmonary hypertension in sickle cell disease. N Engl J Med. 2011;365(1):44–53.
   PubMed Web of Science ®Google Scholar
• Simonneau G, Gatzoulis MA, Adatia I, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D34–D41.
   PubMed Web of Science ®Google Scholar
• 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(9):886–895.
   PubMed Web of Science ®Google Scholar
• Ataga KI, Moore CG, Jones S, et al. Pulmonary hypertension in patients with sickle cell disease: a longitudinal study. Br J Haematol. 2006;134(1):109–115.
   PubMed Web of Science ®Google Scholar
• Onyekwere OC, Campbell A, Teshorne M, et al. Pulmonary hypertension in children and adolescents with sickle cell disease. Pediatr Cardiol. 2008;29(2):309–312.
   PubMed Web of Science ®Google Scholar
• 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(11):1549–1552.
   PubMed Web of Science ®Google Scholar
• 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(7):907–913.
   PubMed Web of Science ®Google Scholar
• Minniti CP, Sable C, Campbell A, et al. Elevated tricuspid regurgitant jet velocity in children and adolescents with sickle cell disease: association with hemolysis and hemoglobin oxygen desaturation. Haematologica. 2009;94(3):340–347.
   PubMed Web of Science ®Google Scholar
• Platt OS, Thorington BD, Brambilla DJ, et al. Pain in sickle cell disease. Rates and risk factors. N Engl J Med. 1991;325(1):11–16.
   PubMed Web of Science ®Google Scholar
• 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. 330(23): 1639–1644. 1994.
   PubMed Web of Science ®Google Scholar
• Castro O, Brambilla DJ, Thorington B, et al. The acute chest syndrome in sickle cell disease: incidence and risk factors. The cooperative study of sickle cell disease. Blood. 1994;84(2):643–649.
   PubMed Web of Science ®Google Scholar
• Milner PF, Kraus AP, Sebes JI, et al. Sickle cell disease as a cause of osteonecrosis of the femoral head. N Engl J Med. 1991;325(21):1476–1481.
   PubMed Web of Science ®Google Scholar
• Vichinsky EP, Neumayr LD, Earles AN, et al., Causes and outcomes of the acute chest syndrome in sickle cell disease. National acute chest syndrome study group. N Engl J Med. 342(25): 1855–1865. 2000.
   PubMed Web of Science ®Google Scholar
• Nath KA, Grande JP, Croatt AJ, et al. Transgenic sickle mice are markedly sensitive to renal ischemia-reperfusion injury. Am J Pathol. 2005;166(4):963–972.
   PubMed Web of Science ®Google Scholar
• Juncos JP, Grande JP, Croatt AJ, et al. Early and prominent alterations in hemodynamics, signaling, and gene expression following renal ischemia in sickle cell disease. Am J Physiol Renal Physiol. 2010;298(4):F892–F899.
   PubMed Web of Science ®Google Scholar
• Baddam S, Aban I, Hilliard L, et al. Acute kidney injury during a pediatric sickle cell vaso-occlusive pain crisis. Pediatr Nephrol. 2017;32(8):1451–1456.
   PubMed Web of Science ®Google Scholar
• Ghosh S, Adisa OA, Chappa P, et al. Extracellular hemin crisis triggers acute chest syndrome in sickle mice. J Clin Invest. 2013;123(11):4809–4820.
   PubMed Web of Science ®Google Scholar
• Jain S, Bakshi N, Krishnamurti L. Acute chest syndrome in children with sickle cell disease. Pediatr Allergy Immunol Pulmonol. 2017;30(4):191–201.
   PubMed Web of Science ®Google Scholar
• Pichon A, Connes P, Quidu P, et al. Acetazolamide and chronic hypoxia: effects on haemorheology and pulmonary haemodynamics. Eur Respir J. 2012;40(6):1401–1409. Epub 2012 Apr 20.
   PubMed Web of Science ®Google Scholar
• Betticher DC, Reinhart WH, Geiser J. Effect of RBC shape and deformability on pulmonary O2 diffusing capacity and resistance to flow in rabbit lungs. J Appl Physiol. 1995;8(3):778–783.
   Google Scholar
• Baskurt OK, Meiselman HJ. RBC aggregation: more important that RBC adhesion to endothelial cells as a determinant of in vivo blood flow in health and disease. Microcirculation. 2008;15(7):585–590.
   PubMed Web of Science ®Google Scholar
• Lamarre Y, Romana M, Waltz X, et al. Hemorheological risk factors of acute chest syndrome and painful vaso-occlusive crisis in children with sickle cell disease. Haematologica. 2012;97(11):1641–1647.
   PubMed Web of Science ®Google Scholar
• Renoux C, Connes P, Nader E, et al. Alpha-thalassaemia promotes frequent vaso-occlusive crises in children with sickle cell anaemia through haemorheological changes. Pediatr Blood Cancer. 2017;64(8):e26455.
   PubMed Web of Science ®Google Scholar
• Steinberg MH. Predicting clinical severity in sickle cell anaemia. Br J Haematol. 2005;129(4):465–481.
   PubMed Web of Science ®Google Scholar
• Saraf SL, Akingbola TS, Shah BN, et al. Associations of a-thalassemia and BCL11A with stroke in Nigerian, United States, and United Kingdom sickle cell anemia cohorts. Blood Adv. 2017;1(11):693–698.
   PubMed Web of Science ®Google Scholar
• Belcher JD, Chen C, Nguyen J, et al. Heme triggers TLR4 signaling leading to endothelial cell activation and vaso-occlusion in murine sickle cell disease. Blood. 2014;123(3):377–390. .
   PubMed Web of Science ®Google Scholar
• Manwani D, Frenette PS. Vaso-occlusion in sickle cell disease: pathophysiology and novel targeted therapies. Blood. 2013;122(24):3892–3898.
   PubMed Web of Science ®Google Scholar
• Space SL, Lane PA, Pickett CK, et al. Nitric oxide attenuates normal and sickle red blood cell adherence to pulmonary endothelium. Am J Hematol. 2000;63(4):200–204.
   PubMed Web of Science ®Google Scholar
• Canalli AA, Franco-Penteado CF, Saad ST, et al. Increased adhesive properties of neutrophils in sickle cell disease may be reversed by pharmacological nitric oxide donation. Haematologica. 2008;93(4):605–609.
   PubMed Web of Science ®Google Scholar
• 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(1):60–68.
   PubMed Web of Science ®Google Scholar
• Gutsaeva DR, Montero-Huerta P, Parkerson JB, et al. Molecular mechanisms underlying synergistic adhesion of sickle red blood cells by hypoxia and low nitric oxide bioavailability. Blood. 2014;123(12):1917–1926.
   PubMed Web of Science ®Google Scholar
• Nur E, Biemond BJ, Otten HM, et al., CURAMA Study Group. Oxidative stress in sickle cell disease; pathophysiology and potential implications for disease management. Am J Hematol. 2011;86(6):484–489.
   PubMed Web of Science ®Google Scholar
• Voskou S, Aslan M, Fanis P, et al. Oxidative stress in ß-thalassaemia and sickle cell disease. Redox Biol. 2015;6:226–239.
   PubMed Web of Science ®Google Scholar
• Amer J, Ghoti H, Rachmilewitz E, et al. Red blood cells, platelets and polymorphonuclear neutrophils of patients with sickle cell disease exhibit oxidative stress that can be ameliorated by antioxidants. Br J Haematol. 2006;132(1):108–113.
   PubMed Web of Science ®Google Scholar
• Camus SM, De Moraes JA, Bonnin P, et al. Circulating cell membrane microparticles transfer heme to endothelial cells and trigger vasoocclusions in sickle cell disease. Blood. 2015;125(24):3805–3814.
   PubMed Web of Science ®Google Scholar
• Villagra J, Shiva S, Hunter LA, et al. Platelet activation in patients with sickle disease, hemolysis-associated pulmonary hypertension, and nitric oxide scavenging by cell-free hemoglobin. Blood. 2007;110(6):2166–2172.
   PubMed Web of Science ®Google Scholar
• Dominical VM, Samsel L, Nichols JS, et al. Prominent role of platelets in the formation of circulating neutrophil-red cell heterocellular aggregates in sickle cell anemia. Haematologica. 2014;99(11):e214–e217.
   PubMed Web of Science ®Google Scholar
• Bennewitz MF, Jimenez MA, Vats R, et al. Lung vaso-occlusion in sickle cell disease mediated by arteriolar neutrophil-platelet microemboli. JCI Insight. 2017;2(1):e89761. .
   PubMed Web of Science ®Google Scholar
• Nebor D, Bowers A, Hardy-Dessources MD, et al., Frequency of pain crises in sickle cell anemia and its relationship with the sympatho-vagal balance, blood viscosity and inflammation. Haematologica. 96(11): 1589–1594. 2011.
   PubMed Web of Science ®Google Scholar
• Kaul DK, Hebbel RP. Hypoxia/reoxygenation causes inflammatory response in transgenic sickle mice but not in normal mice. J Clin Invest. 2000;106(3):411–420.
   PubMed Web of Science ®Google Scholar
• Hebbel RP. Ischemia-reperfusion injury in sickle cell anemia: relationship to acute chest syndrome, endothelial dysfunction, arterial vasculopathy, and inflammatory pain. Hematol Oncol Clin North Am. 2014;28(2):181–198.
   PubMed Web of Science ®Google Scholar
• Eltzschig HK, Eckle T. Ischemia and reperfusion–from mechanism to translation. Nat Med. 2011;17(11):1391–1401.
   PubMed Web of Science ®Google Scholar
• Carden DL, Granger DN. Pathophysiology of ischaemia-reperfusion injury. J Pathol. 2000;190(3):255–266.
   PubMed Web of Science ®Google Scholar
• Kalogeris T, Baines CP, Krenz M, et al. Cell biology of ischemia/reperfusion injury. Int Rev Cell Mol Biol. 2012;298:229–317.
   PubMed Web of Science ®Google Scholar
• Wallace KL, Linden J. Adenosine A2A receptors induced on iNKT and NK cells reduce pulmonary inflammation and injury in mice with sickle cell disease. Blood. 2010;116(23):5010–5020.
   PubMed Web of Science ®Google Scholar
• Osarogiagbon UR, Choong S, Belcher JD, et al. Reperfusion injury pathophysiology in sickle transgenic mice. Blood. 2000;96(1):314–320.
   PubMed Web of Science ®Google Scholar
• Polanowska-Grabowska R, Wallace K, Field JJ, et al. P-selectin-mediated platelet-neutrophil aggregate formation activates neutrophils in mouse and human sickle cell disease. Arterioscler Thromb Vasc Biol. 2010;30(12):2392–2399.
   PubMed Web of Science ®Google Scholar
• Luo W, Campbell A, Wang H, et al. P-selectin glycoprotein ligand-1 inhibition blocks increased leukocyte-endothelial interactions associated with sickle cell disease in mice. Blood. 2012;120(18):3862–3864.
   PubMed Web of Science ®Google Scholar
• Ataga KI, Kutlar A, Kanter J, et al., Crizanlizumab for the prevention of pain crises in sickle cell disease. N Engl J Med. 376(5): 429–439. 2017.
   PubMed Web of Science ®Google Scholar
• ADAKVEO (crizanlizumab-tmca) injection [prescribing information]. East Hanover (NJ): Novartis Pharmaceuticals Corp; 2019.
   Google Scholar
• Ghosh S, Flage B, Weidert F, et al. P-selectin plays a role in haem-induced acute lung injury in sickle mice. Br J Haematol. 2019;186(2):329–333.
   PubMed Web of Science ®Google Scholar
• Magnani JL, Sarkar A, Li Y, et al. GMI-1070: a small pan-selectin antagonist that inhibits leukocyte adhesion and migration in multiple disease models in vivo. Blood. 2007;110(11):2410.
   Web of Science ®Google Scholar
• Edwards EE, Oh J, Anilkumar A, et al. P-, but not E- or L-, selectin-mediated rolling adhesion persistence in hemodynamic flow diverges between metastatic and leukocytic cells. Oncotarget. 2017;8(48):83585–83601.
   PubMedGoogle Scholar
• Telen MJ, Wun T, McCavit TL, et al. Randomized phase 2 study of GMI-1070 in SCD: reduction in time to resolution of vaso-occlusive events and decreased opioid use. Blood. 2015;125(17):2656–2664.
   PubMed Web of Science ®Google Scholar
• Pfizer Inc. Pfizer announces phase 3 top-line results for rivipansel in patients with sickle cell disease experiencing a vaso-occlusive crisis [press release]. 2019 Aug 2. [cited 2019 Dec 6]. Available from: https://www.pfizer.com/news/press-release/press-release-detail/pfizer_announces_phase_3_top_line_results_for_rivipansel_in_patients_with_sickle_cell_disease_experiencing_a_vaso_occlusive_crisis
   Google Scholar
• Akinsheye I, Alsultan A, Solovieff N, et al., Fetal hemoglobin in sickle cell anemia. Blood. 118(1): 19–27. 2011.
   PubMed Web of Science ®Google Scholar
• Molokie R, Lavelle D, Gowhari M, et al. Oral tetrahydrouridine and decitabine for non-cytotoxic epigenetic gene regulation in sickle cell disease: a randomized phase 1 study. PLoS Med. 2017;14(9):e1002382. .
   PubMed Web of Science ®Google Scholar
• Niihara Y, Miller ST, Kanter J, et al. A phase 3 trial of l-glutamine in sickle cell disease. N Engl J Med. 2018;379(3):226–235. .
   PubMed Web of Science ®Google Scholar
• Ribeil JA, Hacein-Bey-Abina S, Payen E, et al., Gene therapy in a patient with sickle cell disease. N Engl J Med. 376(9): 848–855. 2017.
   PubMed Web of Science ®Google Scholar
• Heeney MM, Hoppe CC, Abboud MR, et al. A multinational trial of prasugrel for sickle cell vaso-occlusive events. N Engl J Med. 2016;374(7):625–635.
   PubMed Web of Science ®Google Scholar
• Hoppe CC, Styles L, Heath LE, et al. Design of the DOVE (Determining Effects of Platelet Inhibition on Vaso-Occlusive Events) trial: a global phase 3 double-blind, randomized, placebo-controlled, multicenter study of the efficacy and safety of prasugrel in pediatric patients with sickle cell anemia utilizing a dose titration strategy. Pediatr Blood Cancer. 2016;63(2):299–305.
   PubMed Web of Science ®Google Scholar
• Adebiyi MG, Manalo JM, Xia Y. Metabolomic and molecular insights into sickle cell disease and innovative therapies. Blood Adv. 2019;3(8):1347–1355.
   PubMed Web of Science ®Google Scholar