Presence of paroxysmal nocturnal hemoglobinuria in patients with idiopathic portal vein thrombosis: a single-center study

Background/aim: Paroxysmal nocturnal hemoglobinuria (PNH) is a very rare clonal hematopoietic stem cell disease characterized by chronic hemolytic anemia and thrombosis. We report data from a study of the occurrence of PNH among patients with idiopathic portal vein thrombosis (PVT). Materials and methods: Patients who were followed up with the diagnosis of idiopathic PVT were enrolled into this study. Those with laboratory and/or imaging evidence of any local or systemic factor that could lead to PVT were excluded. PNH clone was examined in all patients using established FLAER methodology. Results: A total of 112 patients (42 males and 70 females), none of them had a markedly PNH clone, but 4 patients (3.6%) with confirmed tests two times had small PNH clones (size between 3.02% and 4.62%). The median ages of PNH clone (-) and PNH clone (+) patients were 42 (range; 24–59) vs 39 (range; 36–42) years, respectively. The median hemoglobin concentration, platelet count and leukocyte count were lower in the PNH clone (+) group than the PNH clone (-) group. Anemia, thrombocytopenia, and leukopenia were detected in all PNH clone (+) patients. In addition, the PNH clone positivity size in monocytes was higher than erythrocytes in all of 4 patients. Conclusions: PNH should be considered during differential diagnosis among patients with idiopathic PVT. Small PNH clones can be detected in PVT patients that we cannot clearly determine its relationship with PVT. We need furthermore studies to explore the potential role of this finding.

PDF

___

1. Hillmen P, Lewis SM, Bessler M, Luzzatto L, Dacia JV. Natural history of paroxysmal nocturnal hemoglobinuria. The New England Journal of Medicine 1995; 333 (19): 1253-1258.
2. Parker CJ. Paroxysmal nocturnal hemoglobinuria. Current Opinion in Hematology 2012; 19 (3): 141-148.
3. Devalet B, Mullier F, Chatelain B, Dogné JM, Chatelain C. Pathophysiology, diagnosis, and treatment of paroxysmal nocturnal hemoglobinuria: a review. European Journal of Haematology 2015; 95 (3): 190-198.
4. Hill A, Ridley SH, Esser D, Oldroyd RG, Cullen MJ et al. Protection of erythrocytes from human complement-mediated lysis by membrane-targeted recombinant soluble CD59: a new approach to PNH therapy. Blood 2006; 107 (5): 2131-2137.
5. Parker C, Omine M, Richards S, Nishimura J, Bessler M et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood 2005; 106 (12): 3699-3709.
6. Hill A, Kelly RJ, Hillmen P. Thrombosis in paroxysmal nocturnal hemoglobinuria. Blood 2013; 121 (25): 4985-4996.
7. Dirik Y, Ekinci Ö, Kara O, Dirik D, Doğan A et al. The role of paroxysmal nocturnal hemoglobinuria in idiopathic habitual abortion. Eastern Journal of Medicine 2017; 22 (4): 143-146.
8. Ekinci Ö, Doğan A, Demir C. The presence of paroxysmal nocturnal hemoglobinuria in patients with idiopathic chronic renal failure. Eastern Journal of Medicine 2017; 22 (4): 133-136.
9. Borowitz MJ, Craig FE, Digiuseppe JA, Illingworth AJ, Rosse W et al. Guidelines for the diagnosis and monitoring of paroxysmal nocturnal hemoglobinuria and related disorders by flow cytometry. Cytometry. Part B, Clinical Cytometry 2010; 78 (4): 211-230.
10. Sutherland DR, Keeney M, Illingworth A. Practical guidelines for the high-sensitivity detection and monitoring of paroxysmal nocturnal hemoglobinuria clones by flow cytometry. Cytometry Part B Clinical Cytometry 2012; 82 (4): 195-208.
11. Ponziani FR, Zocco MA, Campanale C, Rinninella E, Tortora A et al. Portal vein thrombosis: insight into physiopathology, diagnosis, and treatment. World Journal of Gastroenterology 2010; 16 (2): 143-155.
12. Lee JW, Jang JH, Kim JS, Yoon SS, Lee JH et al. Clinical signs and symptoms associated with increased risk for thrombosis in patients with paroxysmal nocturnal hemoglobinuria from a Korean Registry. International Journal of Hematology 2013; 97 (6): 749-757.
13. Hillmen P, Muus P, Dührsen U, Risitano AM, Schubert J et al. Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria. Blood 2007; 110 (12): 4123-4128.
14. Gayer G, Zandman-Goddard G, Raanani P, Hertz M, Apter S. Widespread abdominal venous thrombosis in paroxysmal nocturnal hemoglobinuria diagnosed on CT. Abdominal Imaging 2001; 26 (4): 414-419.
15. Tomizuka H, Hatake K, Kitagawa S, Yamashita K, Arai H et al. Portal vein thrombosis in paroxysmal nocturnal haemoglobinuria. Acta Haematologica 1999; 101 (3): 149-152.
16. Schmets L, Hagège H, Merlet C, Zylberberg H, Chousterman M. Porto-hepatic thrombosis, revealing paroxysmal nocturnal hemoglobinuria, followed by regression induced by heparin therapy. Gastroentérologie Clinique et Biologique 1993; 17 (12): 955-958.
17. Socié G, Mary JY, De Gramont A, Rio B, Leporrier M et al. Paroxysmal nocturnal haemoglobinuria: long-term follow-up and prognostic factors. French Society of Haematology. Lancet 1996; 348 (9027): 573-577.
18. Ekinci O, Dogan A, Demircioglu S, Sonmez GM, Demir C. Clinical features and responses to eculizumab of paroxysmal nocturnal hemoglobinuria patients: a single-center experience. Medicine Science 2019; 8 (3): 624-627.
19. Moyo VM, Mukhina GL, Garrett ES, Brodsky RA. Natural history of paroxysmal nocturnal haemoglobinuria using modern diagnostic assays. British Journal of Haematology 2004; 126 (1): 133-138.
20. Nishimura J, Kanakura Y, Ware RE, Shichishima T, Nakakuma H et al. Clinical course and flow cytometric analysis of paroxysmal nocturnal hemoglobinuria in the United States and Japan. Medicine (Baltimore) 2004; 83 (3): 193-207.
21. Ageno W, Dentali F, De Stefano V, Barco S, Lerede T et al. Clonal populations of hematopoietic cells with paroxysmal nocturnal hemoglobinuria phenotype in patients with splanchnic vein thrombosis. Thrombosis Research 2014; 133 (6): 1052-1055.
22. Ahluwalia J, Naseem S, Sachdeva MU, Bose P, Bose SK et al. Paroxysmal Nocturnal Hemoglobinuria is rare cause for thrombosis of the intra-abdominal veins in the ethnic Indian population - results from FLAER-based flowcytometry screening. European Journal of Haematology 2014; 92 (5): 435- 443.
23. Qi X, He C, Han G, Yin Z, Wu F et al. Prevalence of paroxysmal nocturnal hemoglobinuria in Chinese patients with BuddChiari syndrome or portal vein thrombosis. Journal of Gastroenterology and Hepatology 2013; 28 (1): 148-152.
24. Pu JJ, Brodsky RA. Paroxysmal nocturnal hemoglobinuria from bench to bedside. Clinical and Translational Science 2011; 4 (3): 219-224.