Walter Ageno1, Francesco Dentali2, Valerio De Stefano3, Stefano Barco4, Teresa Lerede5, Mario Bazzan6, Antonietta Piana7, Rita Santoro8, Rita Duce9, Daniela Poli10, Ida Martinelli11, Sergio Siragusa12, Giovanni Barillari13, Marco Cattaneo14, Gianpaolo Vidili15, Monica Carpenedo16, Elena Rancan2, Ilaria Giaretta17, Alberto Tosetto17. 1. Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy. Electronic address: agewal@yahoo.com. 2. Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy. 3. Institute of Hematology, Catholic University, Rome. 4. IRCCS Fondazione Policlinico San Matteo, Pavia, Italy. 5. Department of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy. 6. Department of Hematology, Ospedale S. Giovanni Bosco, Turin, Italy. 7. Department of Internal Medicine, Ospedale S. Martino, Genoa, Italy. 8. Hemophilia and Thrombosis Center, Department of Hematology, Azienda Ospedaliera "Pugliese-Ciaccio", Catanzaro, Italy. 9. Centro Trombosi, S.C. Medicina Interna, Ospedale Galliera, Genoa, Italy. 10. Thrombosis Center, Ospedale Careggi, Florence, Italy. 11. A. Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Internal Medicine and Medical Specialties, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, Italy. 12. U.O. di Ematologia con trapianto, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Italy. 13. Department of Transfusional Medicine, Ospedale S. Maria della Misericordia, Udine, Italy. 14. Medicina 3, Ospedale S.Paolo and Dipartimento di Scienze della Salute, University of Milan, Italy. 15. Clinica Medica, Azienda Ospedaliero Universitaria, Sassari, Italy. 16. U.O.C Ematologia e Centro Trapianti, A.O. San Gerardo di Monza, Italy. 17. Department of Hematology, Ospedale S. Bortolo, Vicenza, Italy.
Abstract
INTRODUCTION: Splanchnic vein thrombosis (SVT) is a serious complication in patients with paroxysmal nocturnal hemoglobinuria (PNH). Mutant PNH clones can be associated with an increased risk of SVT even in the absence of overt disease, but their prevalence in non-selected SVT patients remains unknown. MATERIALS AND METHODS: Patients with objective diagnosis of SVT and without known PNH were tested for the presence of PNH clone using high-sensitivity flow cytometric analysis. RESULTS: A total of 202 SVT patients were eligible, 58.4% were males, mean age was 54.6years (range 17-94), site of thrombosis was portal in 103 patients, mesenteric in 67, splenic in 37, and supra-hepatic in 10. SVT was associated with JAK2 V6167F in 28 of 126 (22.2%) screened patients, liver cirrhosis in 15.3% patients, recent surgery in 10.9%, and myeloproliferative neoplasm in 10.6%, whereas in 34.6% of patients neither permanent nor transient risk factors were detected. None of the patients had a clearly demonstrable PNH clone, but in two patients (0.99%, 95% CI 0.17-3.91) we observed very small PNH clones (size 0.014% and 0.16%) confirmed in two independent samples. One patient had portal vein thrombosis and no associated risk factors, the second had superior mesenteric vein thrombosis and inflammatory bowel disease. CONCLUSIONS: Very small PNH clones can be detected in patients with SVT and no clinical manifestations of disease. Future studies are needed to explore the potential role of this finding in the pathogenesis of SVT.
INTRODUCTION:Splanchnic vein thrombosis (SVT) is a serious complication in patients with paroxysmal nocturnal hemoglobinuria (PNH). Mutant PNH clones can be associated with an increased risk of SVT even in the absence of overt disease, but their prevalence in non-selected SVT patients remains unknown. MATERIALS AND METHODS:Patients with objective diagnosis of SVT and without known PNH were tested for the presence of PNH clone using high-sensitivity flow cytometric analysis. RESULTS: A total of 202 SVT patients were eligible, 58.4% were males, mean age was 54.6years (range 17-94), site of thrombosis was portal in 103 patients, mesenteric in 67, splenic in 37, and supra-hepatic in 10. SVT was associated with JAK2 V6167F in 28 of 126 (22.2%) screened patients, liver cirrhosis in 15.3% patients, recent surgery in 10.9%, and myeloproliferative neoplasm in 10.6%, whereas in 34.6% of patients neither permanent nor transient risk factors were detected. None of the patients had a clearly demonstrable PNH clone, but in two patients (0.99%, 95% CI 0.17-3.91) we observed very small PNH clones (size 0.014% and 0.16%) confirmed in two independent samples. One patient had portal vein thrombosis and no associated risk factors, the second had superior mesenteric vein thrombosis and inflammatory bowel disease. CONCLUSIONS: Very small PNH clones can be detected in patients with SVT and no clinical manifestations of disease. Future studies are needed to explore the potential role of this finding in the pathogenesis of SVT.