Paroksismal nokturnal hemoglobinüri
Paroksismal nokturnal hemoglobinüri (PNH) hemolitik anemi ile seyreden edinsel klonal hematopoetik bir kök hücre hastalÕ÷ÕdÕr. Özellikle CD55 ve CD59 gibi yüzey proteinleri, kompleman etkisine karúÕ hücreleri korur ve bu proteinler PNHlÕ mutasyona u÷ramÕú hematopoetik kök hücrelerden kaynaklanan olgun hücrelerde eksiktir. PNH, kronik intravasküler Coombs negative hemolitik anemi, tromboz ve kemik ili÷i yetmezli÷i bulgularÕ ile seyreden bir hastalÕktÕr. AkÕm sitometri, CD55 ve CD59 eksikli÷inin saptanmasÕnda en yaygÕn kullanÕlan tanÕ yöntemidir. PNH tanÕsÕnda FLAER (fluorescent aerolysin) yeni bir yöntemdir. PNHda küratif olan tek tedavi; allojenik kök hücre naklidir (AKHN), fakat mortalite ve morbidite insidansÕ yüksek bir tedavi yöntemidir. AntiC5 monok- lonal antikoru olan eculizumab ile hastalÕ÷Õn en önemli komplikasyonu olan tromboz geliúimi baúta olmak üzere morbidite ve mortalite oranlarÕ azalmÕútÕr. Eculizumab ve yeni geliútirilecek PNH tedavi ajanlarÕ ile PNH da mortalite ve morbiditesi yüksek bir tedavi olan allojenik kök hücre nakline olan gereksinim azalacaktÕr.
Paroxysmal nocturnal hemoglobşnuria
ABSTRACT Paroxysmal nocturnal hemoglobinuria is an acquired clonal hematopoietic stem cell disease undergoing with hemolytic anemia. Surface antigenic proteins, especially like CD55 and CD59, protects cells against the complement effect and these proteins does not exist in PNH mutant hematopoietic stem cell originated mature cells. PNH is a disease presenting with chronic intravascular Coombs negative hemolytic anemia, thrombosis and bone marrow failure. Flow cytometry is the most common diagnosis test in determining CD55 and CD59 deficiency. FLAER (fluorescent aerolysin) is a new method in PNH diagnosis. The only curative treatment is allogenic stem cell transplantation (ASCT) but it has a high incidence of mortality and morbidity. With eculizumab, an anti C5 monoclonal antibody, mortality and morbidity rates and the most important complication; thrombosis, is reduced. Allogenic stem cell transplantation requirement will be reduced with eculizumab and the new medications that are going to be developed for PNH treatment.
___
- 1. Hillmen P, Lewis SM, Bessler M, Luzzatto L, Dacie JV. Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med 1995;333: 1253-8.
- 2. Parker C, Omine M, Richards S, et al. International PNH Interest Group. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood 2005;106:3699-709.
- 3. Kelly RJ, Hill A, Arnold LM, et al. Long-term treatment with eculizumab in paroxysmal nocturnal hemoglobinuria: sustained efficacy and improved survival. Blood 2011; 23:6786-92.
- 4. Parker CJ. Paroxysmal nocturnal hemoglobinuria. Curr Opin Hematol 2012;19:141-8.
- 5. Parker CJ. The pathophysiology of paroxysmal nocturnal hemoglobinuria. Exp Hematol 2007;35:523-33.
- 6. Parker CJ. Hemolysis in PNH. In: Young NS, Moss J, editors. Paroksismal nokturnal hemoglobinüriand the glycosylphosphatidylinositol- linked proteins. San Diego: Academic Press; 2000:49-100.
- 7. Çetiner M. Paroksismal Nokturnal Hemoglobinüri. Turkiye Klinikleri J Hem Onc-Special Topics 2011;4:23-8.
- 8. Socie G, Mary JY, de Gramont A, Rio B, Leporrier M, Rose C, et al.Paroxysmal nocturnal haemoglobinuria: long-term follow-up and prognostic factors. French Society of Haematology. Lancet 1996;348:573-7.
- 9. Rosse WF, Dacie JV. Immune lysis of normal human and paroxysmal nocturnal hemoglobinuria (PNH) red blood cells. I. The sensitivity of PNH red cells to lysis by complement and specific antibody. J Clin Invest 1966;45:736-48.
- 10. 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.
- 11. Hillmen P, Muus P, Dührsen U, et al. Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria. Blood 2007;110:4123-8.
- 12. Paroksismal Nokturnal Hemoglobinüri TanÕ ve Tedavi KÕlavuzu, Kemik øli÷i Yetersizlikleri TanÕ ve Tedavi KÕlavuzu. Türk hematoloji Derne÷i, Ulusal TanÕ ve Tedavi KÕlavuzu, 2011:15-25.
- 13. Brodsky RA, Mukhina GL, Li S, et al. Improved detection and characterization of Paroksismal nokturnal hemoglobinuri using fluorescent aerolysin.Am J Clin Pathol 2000;114(3):459-66.
- 14. Sears DA, Anderson PR, Foy AL, Williams HL, Crosby WH. Al Urinary øron Excretion and Renal Metabolism of Hemoglobin in Hemolytic Diseases. Blood 1966;5:28:708-25.
- 15. Jeffrey J Pu and Robert A. Brodsky Paroxysmal Nocturnal Hemoglobinuria from Bench to Bedside Clin Transl Sci 2011;4:219-24.
- 16. Rother RP, Rollins SA, Mojcik CF, Brodsky RA, Bell L. Discovery and Development of the Complement ønhibition Eculizumab for the Treatment of Paroxysmal Nocturnal Hemoglobinuria Nat. Biotechnol 2007;25:1256-64.
- 17. Schubert J, Hillmen P, Roth A, et al. Eculizumab, a terminal complement inhibitor, improves anaemia in patients with paroxysmal nocturnal haemoglobinuria. Br J Haematol 2008;142:263-72.
- 18. Schrezenmeier H, Höchsmann B. Drugs that inhibit complement. Transfus Apher Sci 2012;4:87-92.