Consequences of Hemolysis
Chronic, complement-mediated intravascular hemolysis is the underlying cause of progressive morbidities and premature mortality in PNH1,10
- Even in the absence of symptoms, hemolysis is ongoing2,15
- The consequences of hemolysis can be unpredictable, sudden, and potentially fatal9
- Hemolysis-induced nitric oxide depletion results in thrombosis, abdominal pain, pulmonary hypertension, dysphagia, and erectile dysfunction12
- Thrombosis is markedly elevated in patients with smaller clones, as low as 10%, when compared to the normal population16
The diverse and common symptomatology of PNH can delay diagnosis15,19
A diagnosis of PNH is typically delayed from 1 to more than 10 years.19 The name of the disease can be misleading, as nearly three-fourths of patients with PNH do not present with hemoglobinuria.6 The wide range of symptoms caused by PNH is shown in the chart below.
The diverse symptomatology of PNH drives the need for a comprehensive clinical assessment and routine diagnostic approach.2,6
Early diagnosis is essential for improved patient management and prognosis. Learn about ICCS and IPIG recommendations for who should be tested for PNH.
Some common symptoms in a patient with PNH can be manifestations of devastating consequences from chronic complement-mediated hemolysis. Learn how a full clinical assessment can uncover signs and symptoms associated with premature mortality in your patient with PNH.
References: 1. Brodsky RA. Blood Rev. 2008;22:65-74. 2. Rachidi S, Musallam KM, Taher AT. A closer look at paroxysmal nocturnal hemoglobinuria. Eur J Intern Med. 2010;21:260-267. 3. Borowitz MJ, Craig FE, DiGiuseppe JA, et al; for Clinical Cytometry Society. Guidelines for the diagnosis and monitoring of paroxysmal nocturnal hemoglobinuria and related disorders by flow cytometry. Cytometry Part B. 2010;78B:211-230. 4. Hillmen P, Elebute M, Kelly R, et al. Am J Hematol. 2010;85:553-559. 5. Kelly R, Richards S, Hillmen P, et al. Ther Clin Risk Manag. 2009;5:911-921. 6. Parker C, Omine M, Richards S, et al; for International PNH Interest Group. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood. 2005;106:3699-3709. 7. Hillmen P, Muus P, Dührsen U, et al. Blood. 2007;110:4123-4128. 8. Adams T, Fleischer D, Marino G, et al. Gastrointestinal involvement in paroxysmal nocturnal hemoglobinuria: first report of electron microscopic findings. Dig Dis Sci. 2002;47:58-64. 9. Brodsky RA. Paroxysmal nocturnal hemoglobinuria. In: Hoffman R, Benz EJ Jr, Shattil SJ, et al, eds. Hematology: Basic Principles and Practice. 4th ed. Philadelphia, PA: Elsevier Churchill Livingstone; 2005:419-427. 10. Hill A, Sapsford RJ, Scally A, et al. Under-recognized complications in patients with paroxysmal nocturnal haemoglobinuria: raised pulmonary pressure and reduced right ventricular function. Br J Haematol. 2012;158:409-414. 11. Hill A, Rother RP, Wang X, et al. Br J Haematol. 2010;149:414-425. 12. Rother RP, Bell L, Hillmen P, et al. The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin: a novel mechanism of human disease. JAMA. 2005;293:1653-1662. 13. Hill A, Richards SJ, Hillmen P. Recent developments in the understanding and management of paroxysmal nocturnal haemoglobinuria. Br J Haematol. 2007;137:181-192. 14. Rother RP, Rollins SA, Mojcik CF, et al. Nat Biotechnol. 2007;25:1256-1264. [Published correction appears in Nat Biotechnol. 2007;25:1488]. 15. Rosse WF. Paroxysmal nocturnal hemoglobinuria. In: Hoffman R, Benz EJ Jr, Shattil SJ, et al, eds. Hematology: Basic Principles and Practice. 3rd ed. New York, NY: Churchill Livingstone; 2000:331-342. 16. Hill A, Kelly R, Hillmen P. Thrombosis in paroxysmal nocturnal hemoglobinuria. Blood. 2013;121:4985-4996. 17. Nishimura J-I, Kanakura Y, Ware RE, et al. Clinical course and flow cytometric analysis of paroxysmal nocturnal hemoglobinuria in the United States and Japan. Medicine. 2004;83:193-207. 18. Weitz I, Meyers G, Lamy T, et al. Cross-sectional validation study of patient-reported outcomes in patients with paroxysmal nocturnal haemoglobinuria. Intern Med J. 2013;43:298-307. 19. Dacie JV, Lewis SM. Ser Haematol. 1972;5:3-23.