title: Clonal populations of hematopoietic cells with paroxysmal nocturnal hemoglobinuria phenotype in patients with splanchnic vein thrombosis.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy. Electronic address: agewal@yahoo.com.
authors.forename: Walter
authors.initials: W
authors.lastname: Ageno
authors.affiliation: Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Dentali
authors.affiliation: Institute of Hematology, Catholic University, Rome.
authors.forename: Valerio
authors.initials: V
authors.lastname: De Stefano
authors.affiliation: IRCCS Fondazione Policlinico San Matteo, Pavia, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Barco
authors.affiliation: Department of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Lerede
authors.affiliation: Department of Hematology, Ospedale S. Giovanni Bosco, Turin, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Bazzan
authors.affiliation: Department of Internal Medicine, Ospedale S. Martino, Genoa, Italy.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Piana
authors.affiliation: Hemophilia and Thrombosis Center, Department of Hematology, Azienda Ospedaliera "Pugliese-Ciaccio", Catanzaro, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Santoro
authors.affiliation: Centro Trombosi, S.C. Medicina Interna, Ospedale Galliera, Genoa, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Duce
authors.affiliation: Thrombosis Center, Ospedale Careggi, Florence, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Poli
authors.affiliation: A. Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Internal Medicine and Medical Specialties, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Ida
authors.initials: I
authors.lastname: Martinelli
authors.affiliation: U.O. di Ematologia con trapianto, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Siragusa
authors.affiliation: Department of Transfusional Medicine, Ospedale S. Maria della Misericordia, Udine, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Barillari
authors.affiliation: Medicina 3, Ospedale S.Paolo and Dipartimento di Scienze della Salute, University of Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Cattaneo
authors.affiliation: Clinica Medica, Azienda Ospedaliero Universitaria, Sassari, Italy.
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Vidili
authors.affiliation: U.O.C Ematologia e Centro Trapianti, A.O. San Gerardo di Monza, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Carpenedo
authors.affiliation: Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Rancan
authors.affiliation: Department of Hematology, Ospedale S. Bortolo, Vicenza, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Giaretta
authors.affiliation: Department of Hematology, Ospedale S. Bortolo, Vicenza, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Tosetto
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003430:Cross-Sectional Studies; D005260:Female; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D020246:Venous Thrombosis / Q000097:blood / Q000473:pathology*; D055815:Young Adult