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Pulmonary Hypertension in Sickle Cell Disease: Current Controversies and Clinical Practices

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Pulmonary Hypertension

Part of the book series: Respiratory Medicine ((RM))

Abstract

Sickle cell disease (SCD), the most common genetic disorder worldwide, affects up to 100,000 people living in the United States and accounts for up to 300,000 births annually worldwide. A hemoglobinopathy characterized by recurrent episodes of hemolysis and vaso-occlusion, SCD adversely affects nearly every vascular bed of the systemic and pulmonary vasculature. The two primary pathogenic mechanisms of SCD are vaso-occlusion and hemolysis, with downstream effects on inflammation, redox biology, nitric oxide (NO) metabolism, and coagulation. The hallmark of vaso-occlusion in SCD is abnormal interactions between erythrocytes, leukocytes, platelets, and the vascular endothelium leading to promotion of inflammation, thrombosis, and oxidative stress [1, 2].

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References

  1. Moerdler S, Manwani D. New insights into the pathophysiology and development of novel therapies for sickle cell disease. Hematol Am Soc Hematol Educ Program. 2018;2018(1):493–506.

    Google Scholar 

  2. Telen MJ, Malik P, Vercellotti GM. Therapeutic strategies for sickle cell disease: towards a multi-agent approach. Nat Rev Drug Discov. 2019;18(2):139–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Mehari A, Alam S, Tian X, Cuttica MJ, Barnett CF, Miles G, et al. Hemodynamic predictors of mortality in adults with sickle cell disease. Am J Respir Crit Care Med. 2013;187(8):840–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Parent F, Bachir D, Inamo J, Lionnet F, Driss F, Loko G, et al. A hemodynamic study of pulmonary hypertension in sickle cell disease. N Engl J Med. 2011;365(1):44–53.

    Article  CAS  PubMed  Google Scholar 

  5. Fonseca GHH, Souza R, Salemi VMC, Jardim CVP, Gualandro SFM. Pulmonary hypertension diagnosed by right heart catheterisation in sickle cell disease. Eur Respir J. 2012;39(1):112–8.

    Article  CAS  PubMed  Google Scholar 

  6. Niss O, Quinn CT, Lane A, Daily J, Khoury PR, Bakeer N, et al. Cardiomyopathy with restrictive physiology in sickle cell disease. JACC Cardiovasc Imaging. 2016;9(3):243–52.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Savale L, Habibi A, Lionnet F, Maitre B, Cottin V, Jais X, et al. Clinical phenotypes and outcomes of precapillary pulmonary hypertension of sickle cell disease. Eur Respir J. 2019;19.

    Google Scholar 

  8. Galiè N, McLaughlin VV, Rubin LJ, Simonneau G. An overview of the 6th World Symposium on Pulmonary Hypertension. Eur Respir J. 2019;53(1).

    Google Scholar 

  9. Simonneau G, Galiè N, Rubin LJ, Langleben D, Seeger W, Domenighetti G, et al. Clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2004;43(12 Suppl S):5S–12S.

    Google Scholar 

  10. Simonneau G, Robbins IM, Beghetti M, Channick RN, Delcroix M, Denton CP, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2009;54(1 Suppl):S43–54.

    Article  PubMed  Google Scholar 

  11. Simonneau G, Gatzoulis MA, Adatia I, Celermajer D, Denton C, Ghofrani A, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D34–41.

    Article  PubMed  Google Scholar 

  12. Machado RF, Barst RJ, Yovetich NA, Hassell KL, Kato GJ, Gordeuk VR, et al. Hospitalization for pain in patients with sickle cell disease treated with sildenafil for elevated TRV and low exercise capacity. Blood. 2011;118(4):855–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Barst RJ, Mubarak KK, Machado RF, Ataga KI, Benza RL, Castro O, et al. Exercise capacity and haemodynamics in patients with sickle cell disease with pulmonary hypertension treated with bosentan: results of the ASSET studies. Br J Haematol. 2010;149(3):426–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. 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(10):1037–43.

    Article  PubMed  Google Scholar 

  15. Carstens GR, Paulino BBA, Katayama EH, Amato-Lourenço LF, Fonseca GH, Souza R, et al. Clinical relevance of pulmonary vasculature involvement in sickle cell disease. Br J Haematol. 2019;185(2):317–26.

    Article  CAS  PubMed  Google Scholar 

  16. Manci EA, Culberson DE, Yang Y-M, Gardner TM, Powell R, Haynes J, et al. Causes of death in sickle cell disease: an autopsy study. Br J Haematol. 2003;123(2):359–65.

    Article  PubMed  Google Scholar 

  17. Galiè N, Humbert M, Vachiery J-L, Gibbs S, Lang I, Torbicki A, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J. 2016;37(1):67–119.

    Google Scholar 

  18. Galiè N, Humbert M, Vachiery J-L, Gibbs S, Lang I, Torbicki A, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Respir J. 2015;46(4):903–75.

    Google Scholar 

  19. Klings ES, Machado RF, Barst RJ, Morris CR, Mubarak KK, Gordeuk VR, et al. An official American Thoracic Society clinical practice guideline: diagnosis, risk stratification, and management of pulmonary hypertension of sickle cell disease. Am J Respir Crit Care Med. 2014;189(6):727–40.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Yawn BP, Buchanan GR, Afenyi-Annan AN, Ballas SK, Hassell KL, James AH, et al. Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members. JAMA. 2014;312(10):1033–48.

    Article  PubMed  Google Scholar 

  21. Klings ES, Anton Bland D, Rosenman D, Princeton S, Odhiambo A, Li G, et al. Pulmonary arterial hypertension and left-sided heart disease in sickle cell disease: clinical characteristics and association with soluble adhesion molecule expression. Am J Hematol. 2008;83(7):547–53.

    Article  CAS  PubMed  Google Scholar 

  22. Gordeuk VR, Campbell A, Rana S, Nouraie M, Niu X, Minniti CP, et al. Relationship of erythropoietin, fetal hemoglobin, and hydroxyurea treatment to tricuspid regurgitation velocity in children with sickle cell disease. Blood. 2009;114(21):4639–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Sokunbi OJ, Ekure EN, Temiye EO, Anyanwu R, Okoromah CAN. Pulmonary hypertension among 5 to 18 year old children with sickle cell anaemia in Nigeria. PLoS One. 2017;12(9):e0184287.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Nguyen K-L, Tian X, Alam S, Mehari A, Leung SW, Seamon C, et al. Elevated transpulmonary gradient and cardiac magnetic resonance-derived right ventricular remodeling predict poor outcomes in sickle cell disease. Haematologica. 2016;101(2):e40–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Gladwin MT, Sachdev V, Jison ML, Shizukuda Y, Plehn JF, Minter K, et al. Pulmonary hypertension as a risk factor for death in patients with sickle cell disease. N Engl J Med. 2004;350(9):886–95.

    Article  CAS  PubMed  Google Scholar 

  26. Kovacs G, Berghold A, Scheidl S, Olschewski H. Pulmonary arterial pressure during rest and exercise in healthy subjects: a systematic review. Eur Respir J. 2009;34(4):888–94.

    Article  CAS  PubMed  Google Scholar 

  27. Simonneau G, Montani D, Celermajer DS, Denton CP, Gatzoulis MA, Krowka M, et al. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J. 2018.

    Google Scholar 

  28. Naik RP, Streiff MB, Haywood C, Segal JB, Lanzkron S. Venous thromboembolism incidence in the cooperative study of sickle cell disease. J Thromb Haemost JTH. 2014;12(12):2010–6.

    Article  CAS  PubMed  Google Scholar 

  29. Brunson A, Lei A, Rosenberg AS, White RH, Keegan T, Wun T. Increased incidence of VTE in sickle cell disease patients: risk factors, recurrence and impact on mortality. Br J Haematol. 2017;178(2):319–26.

    Article  CAS  PubMed  Google Scholar 

  30. Brunson A, Keegan T, Mahajan A, White R, Wun T. High incidence of venous thromboembolism recurrence in patients with sickle cell disease. Am J Hematol. 2019;94(8):862–70.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Kim NH, Delcroix M, Jais X, Madani MM, Matsubara H, Mayer E, et al. Chronic thromboembolic pulmonary hypertension. Eur Respir J. 2018.

    Google Scholar 

  32. Mahesh B, Besser M, Ravaglioli A, Pepke-Zaba J, Martinez G, Klein A, et al. Pulmonary endarterectomy is effective and safe in patients with haemoglobinopathies and abnormal red blood cells: the Papworth experience. Eur J Cardio-Thorac Surg Off J Eur Assoc Cardio-Thorac Surg. 2016;50(3):537–41.

    Article  Google Scholar 

  33. Freeman AT, Ataga KI. Pulmonary endarterectomy as treatment for chronic thromboembolic pulmonary hypertension in sickle cell disease. Am J Hematol. 2015;90(12):E223–4.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Marques MB, Wille KM, Ren Z, Sheth M, McGiffin DC. Successful pulmonary thromboendarterectomy in a patient with sickle cell disease treated with a single preoperative red blood cell exchange. Transfusion (Paris). 2014;54(7):1901–2.

    Article  Google Scholar 

  35. Whitesell PL, Owoyemi O, Oneal P, Nouraie M, Klings ES, Rock A, et al. Sleep-disordered breathing and nocturnal hypoxemia in young adults with sickle cell disease. Sleep Med. 2016;22:47–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Worsham CM, Martin ST, Nouraie S-M, Cohen RT, Klings ES. Clinical and laboratory findings associated with sleep disordered breathing in sickle cell disease. Am J Hematol. 2017;92(12):E649–51.

    Article  PubMed  Google Scholar 

  37. Charache S, Terrin ML, Moore RD, Dover GJ, Barton FB, Eckert SV, et al. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the multicenter study of hydroxyurea in sickle cell Anemia. N Engl J Med. 1995;332(20):1317–22.

    Article  CAS  PubMed  Google Scholar 

  38. Voskaridou E, Christoulas D, Bilalis A, Plata E, Varvagiannis K, Stamatopoulos G, et al. The effect of prolonged administration of hydroxyurea on morbidity and mortality in adult patients with sickle cell syndromes: results of a 17-year, single-center trial (LaSHS). Blood. 2010;115(12):2354–63.

    Article  CAS  PubMed  Google Scholar 

  39. Tsitsikas DA, Seligman H, Sirigireddy B, Odeh L, Nzouakou R, Amos RJ. Regular automated red cell exchange transfusion in the management of pulmonary hypertension in sickle cell disease. Br J Haematol. 2014;167(5):707–10.

    Article  PubMed  Google Scholar 

  40. Turpin M, Chantalat-Auger C, Parent F, Driss F, Lionnet F, Habibi A, et al. Chronic blood exchange transfusions in the management of pre-capillary pulmonary hypertension complicating sickle cell disease. Eur Respir J. 2018;52(4).

    Google Scholar 

  41. Ataga KI, Moore CG, Hillery CA, Jones S, Whinna HC, Strayhorn D, et al. Coagulation activation and inflammation in sickle cell disease-associated pulmonary hypertension. Haematologica. 2008;93(1):20–6.

    Article  CAS  PubMed  Google Scholar 

  42. Shet AS, Wun T. How I diagnose and treat venous thromboembolism in sickle cell disease. Blood. 2018;132(17):1761–9.

    Google Scholar 

  43. Liem RI, Lanzkron SD, Coates T, Decastro L, Desai AA, Ataga KI, et al. American Society of Hematology 2019 guidelines for sickle cell disease: cardiopulmonary and kidney disease. Blood Adv. 2019;3(23):3867–97.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Derchi G, Forni GL, Formisano F, Cappellini MD, Galanello R, D’Ascola G, et al. Efficacy and safety of sildenafil in the treatment of severe pulmonary hypertension in patients with hemoglobinopathies. Haematologica. 2005;90(4):452–8.

    CAS  PubMed  Google Scholar 

  45. Minniti CP, Machado RF, Coles WA, Sachdev V, Gladwin MT, Kato GJ. Endothelin receptor antagonists for pulmonary hypertension in adult patients with sickle cell disease. Br J Haematol. 2009;147(5):737–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Weir NA, Conrey A, Lewis D, Mehari A. Riociguat use in sickle cell related chronic thromboembolic pulmonary hypertension: a case series. Pulm Circ. 2018;8(4):2045894018791802.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Weir NA, Saiyed R, Alam S, Conrey A, Desai HD, George MP, et al. Prostacyclin-analog therapy in sickle cell pulmonary hypertension. Haematologica. 2017;102(5):e163–5.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Machado RF, Martyr S, Kato GJ, Barst RJ, Anthi A, Robinson MR, et al. Sildenafil therapy in patients with sickle cell disease and pulmonary hypertension. Br J Haematol. 2005;130(3):445–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Weatherald J, Savale L, Humbert M. Medical Management of Pulmonary Hypertension with unclear and/or multifactorial mechanisms (group 5): is there a role for pulmonary arterial hypertension medications? Curr Hypertens Rep. 2017;19(11):86.

    Article  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Université Paris-Saclay, School of Medicine, Le Kremlin-Bicêtre, France

    Laurent Savale & Marc Humbert

  2. INSERM UMR_S 999 “Pulmonary Hypertension: Pathophysiology and Novel Therapies”, Hôpital Marie Lannelongue, Le Plessis-Robinson, France

    Laurent Savale & Marc Humbert

  3. Assistance Publique - Hôpitaux de Paris (AP-HP), Department of Respiratory and Intensive Care Medicine, Pulmonary Hypertension National Referral Center, Hôpital Bicêtre, Le Kremlin-Bicêtre, France

    Laurent Savale & Marc Humbert

  4. The Pulmonary Center, Boston University School of Medicine, Boston, MA, USA

    Elizabeth S. Klings

Authors
  1. Laurent Savale
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  2. Marc Humbert
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  3. Elizabeth S. Klings
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Corresponding author

Correspondence to Elizabeth S. Klings .

Editor information

Editors and Affiliations

  1. Division of Pulmonary and Critical Care Medicine, Department of Medicine Pulmonary Hypertension Program University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    H. James Ford

  2. Department of Pulmonary, and Critical Care Medicine, Respiratory Institute, Cleveland Clinic, Cleveland, OH, USA

    Gustavo A. Heresi

  3. Division of Pulmonary Allergy and Critical Care Medicine, Pittsburgh Heart, Lung Blood and Vascular Medicine Institute University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Michael G. Risbano

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Savale, L., Humbert, M., Klings, E.S. (2020). Pulmonary Hypertension in Sickle Cell Disease: Current Controversies and Clinical Practices. In: Ford, H.J., Heresi, G.A., Risbano, M.G. (eds) Pulmonary Hypertension. Respiratory Medicine. Humana, Cham. https://doi.org/10.1007/978-3-030-52787-7_8

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  • DOI: https://doi.org/10.1007/978-3-030-52787-7_8

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