PAROXYSMAL NOCTURNAL HEMOGLOBINURIA - RECOMMENDATIONS FOR DIAGNOSIS AND EXAMINATION OF THE PATIENT POPULATION IN SLOVENIA
Abstract
Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired disease associated with hemolytic anemia, bone marrow failure, thrombosis, and, frequently, poor quality of life. It is caused by defects in the membrane of blood cells, where there is a lack of protein on the cell surface, which inhibits complement activation. We wanted to know the recognition of the disease in Slovenia and the incidence. We prepared the recommendations for discovering of the disease.
Patients and methods: We collected data of 68 patients with prospective analysis of one – year period from 1.10.2013 to 30.9.2014 whose blood was sent to the laboratory of immunology and cytology because of suspected presence of PNH clone. The analysis of peripheral blood was performed with multiparametric high specific flow cytometry in a specialized laboratory KO of Haematology University Medical Centre in Ljubljana.
Results: PNH clone was positive in 13/68 (19%) patients, 55/68 (81%) patients had a negative PNH clone, most positive samples were sent from the University Medical Centre Ljubljana (7/13). 4/13 positive patients were newly discovered. In average the incidence through 10-years was 1,3 / 1,000,000 population/year. The most common cause of PNH patient referral to a specialist hematologist was unexplained cytopenia - 12/13 (92.3%), the most common symptoms were fatigue and dyspnea (100%), in 2/13 patients was present dark urine with hemoglobinuria, 2/13 patients had transient renal insufficiency. 11/13 patients with positive PNH clone had associated a bone marrow failure (aplastic anemia or myelodysplastic syndrome). The size of PNH clone varied from patient to patient.
Conclusions: Early identification of PNH is a key to effective treatment and survival of patients. We recommend determining PNH clone at Coombs negative hemolytic anemia, hemoglobinuria, an unexplained cytopenia, aplastic anemia, myelodysplastic syndrome with laboratory evidence of haemolysis and unexplained thrombosis.
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References
Parker C, Omine M, Richards S, Nishimura J, Bessler M, Were R, et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood. 2005; 106 (12): 3699–709.
Schubert J, Röth A, Bettelheim P, Stüssi G, Brümmendorf TH, Schrezenmeier H. Paroxysmal nocturnal hemoglobinuria (PNH). Oncopedia guidelines 2012. Dosegljivo s spletne strani: http://www.onkopedia-guidelines.info/en/onkopedia/guidelines/paroxysmal-nocturnal-hemoglobinuria-pnh.
Parker CJ. Management of paroxysmal nocturnal hemoglobinuria in the era of complement inhibitory therapy. Hematology Am Socie Hematol Educ Program. 2011; 2011: 21–9.
Risitano A, Rotoli B. Paroxysmal nocturnal hemoglobinuria: pathophysiology, natural history and treatment options in the era of biological agents. Biologics. 2008; 2: 205–22.
Hillmen P, Lewis SM, Bessler M, Luzzatto L, Dacie JV. Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1995; 333: 1253–8.
Borowitz M, Craig F, DiGiuseppe J, Illingworth A, Rosse W, Sutherland R, et al. Guidelines for the diagnosis and monitoring of paroxysmal nocturnal hemoglobinuria and related disorders by flow citometry. Cytometry B Clin Cytom. 2010; 78: 211–30.
Socie G, Mary J, Gramont A, Rio B. Paroxysmal nocturnal hemoglobinuria: long term follow up and prognostic factors. Te Lancet. 1996; 348: 573–7.
Sutherland DR, Keeney M, Illinyworth A. Practical guidelines for the high sensitivity detection and monitoring of paroxysmal nocturnal hemoglobinuria clones by flow cytometry. Cytometry B Clin Cytom. 2012; 82: 195–208.
Sharma VR. Paroxysmal nocturnal hemoglobinuria: pathogenesis, testing and diagnosis. Clin Adv Hematol Oncol. 2013; 11 Suppl 13(9): 2–8.
Hillmen P, Elebute M, Kelly R, Urbano-Isizua A, Hill A, Rother RP, et al. Long-term effect of the complement inhibitor eculizumab on kidney function in patients with paroxysmal nocturnal hemoglobinuria. Am J Hematol. 2010; 85: 553–9.
Brodsky RA, Schrier SL, Tirnauer JS. Clinical manifestations and diagnosis of paroxysmal nocturnal hemoglobinuria. UpToDate 2016. Doseljgivo s spletne strani: http://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-paroxysmal-nocturnal-hemoglobinuria.
Brodsky RA, Schrier SL, Tirnauer JS. Treatment and prognosis of paroxysmal nocturnal hemoglobinuria. UpToDate 2016. Dosegljivo s spletne strani: http://www.uptodate.com/contents/treatment-and-prognosis-of-paroxysmal-nocturnal-hemoglobinuria/.
Luzzatto L, Gianfaldoni G, Notaro R. Management of paroxysmal nocturnal hemoglobinuria: a personal view. Br J Haematol. 2011; 153: 709–72.
Schrezenmeier H, Muus P, Socie G, Szer J, Urbano-Ispizua A, Maciejewski JP, et al. Baseline characteristics and disease burden in patients in the international paroxysmal nocturnal hemoglobinuria registry. Haematologica .2014; 99: 922–9.
Kelly RJ, Hill A, Arnold LM, Brooksbank GL, Richards SJ, Cullen M, et al. Long term treatment with eculizumab in paroxysmal nocturnal hemoglobinuria: sustained efcacy and improved survival. Blood. 2011; 117: 6786–92.
Hillmen P, Muus P, Dührsen U, Risitano AM, Schubert J, Luzzatto L, et al. Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria. Blood. 2007; 110: 4123–8.
Hillmen P, Young NS, Schubert J, Brodsky RA, Socie G, Muus P, et al. Te complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2006; 355: 1233–43.
Preložnik Zupan I. Paroksizmalna nočna hemoglobinurija – prve izkušnje zdravljenja z ekulizumabom pri slovenskih bolnikih.
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