Supplementary Online Content

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1 Supplementary Online Content Ageno W, Riva N, Schulman S, et al. Long-term clinical outcomes of splanchnic vein thrombosis: results of an international registry. JAMA Intern Med. Published online July 13, doi: /jamainternmed eappendix. List of Investigators and Participating Centers efigure. Kaplan-Meier Curves for the Cumulative Incidence of Major Bleeding Events (A) and Thrombotic Events (B) in Patients With Hematological Cancer (54 Patients, Including 49 With Myeloproliferative Neoplasms) and Solid Cancer etable 1. Characteristics of Thrombotic Events etable 2. Multivariate Analysis for Major Bleeding etable 3. Multivariate Analysis for Thrombotic Events etable 4. Tests of Interactions for Major Bleeding Events etable 5. Tests of Interactions for Thrombotic Events This supplementary material has been provided by the authors to give readers additional information about their work American Medical Association. All rights reserved. 1

2 Appendix. List of investigators and participating centers Soo-Mee Bang, Jeong-Ok Lee. Department of Internal Medicine, Seoul National University, South Korea (124 patients). Marco Senzolo, Kryssia Rodriguez, Maria Teresa Sartori, Multivisceral Transplant Unit, Gastroenterology, University Hospital of Padova and Clinical Medicine I, University Hospital of Padova, Italy (81 patients). Elvira Grandone, Donatella Colaizzo, Marianna Guardascione. IRCCS Casa Sollievo della Sofferenza, S. Giovanni Rotondo, and A.O.R.N. Ospedale Cardarelli, Napoli, Italy (49 patients). Jan Beyer-Westendorf. Svenn Pannach, Center for Vascular Medicine and Department of Medicine III, Division of Angiology, University Hospital Carl Gustav Carus Dresden, Germany (44 patients). Samantha Pasca, Giovanni Barillari. Center for Hemorrhagic and Thrombotic Diseases, University Hospital, Udine, Italy (33 patients). Elena Rancan. Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy (26 patients). Matteo Nicola Dario Di Minno. Unit of cell and molecular biology in cardiovascular diseases, Centro Cardiologico Monzino, IRCCS, Milan, Italy (23 patients). Sam Schulman. Department of Medicine, McMaster University, Hamilton, Ontario, Canada (22 patients). Renzo Poggio, Rita Duce. Thrombosis Center, Galliera Hospital, Genoa, Italy (21 patients). Alessandra Malato. Cattedra ed UO di Ematologia con Trapianto, Policlinico Universitario di Palermo, Italy (21 patients). Rita Santoro. Haemophilia Center, Azienda Ospedaliera Pugliese-Ciaccio, Catanzaro, Italy (20 patients). Daniela Poli. Thrombosis Center, Careggi Hospital, Florence, Italy (17 patients). Peter Verhamme. Vascular Medicine and Haemostasis, University of Leuven, Leuven, Belgium (15 patients). Ida Martinelli, Serena M. Passamonti. A. Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca Granda - Ospedale Maggiore Policlinico, Milan, Italy (15 patients). Pieter Kamphuisen. University of Groningen, the Netherlands (12 patients) American Medical Association. All rights reserved. 2

3 Adriano Alatri. Centro Emostasi e Trombosi, A.O. Istituti Ospitalieri di Cremona, Italy (11 patients). Doyeun Oh. Department of Internal Medicine, Pochon CHA University, Seoul, Korea (11 patients). Elbio Antonio D Amico. Hospital das Clínicas da Faculdade de Medicina, Universidade de Sao Paulo, Brazil (10 patients). Cecilia Becattini. Department of Internal and Vascular Medicine, University of Perugia, Ospedale S. Maria della Misericordia, Perugia, Italy (7 patients). Eugenio Bucherini. Ospedale di Faenza, Italy (6 patients). Antonietta Piana. Department of Internal Medicine, University of Genoa, Italy (5 patients). Valerio De Stefano, Silvia Betti. Institute of Hematology, Catholic University, Rome, Italy (5 patients). Gianpaolo Vidili. Department of Clinical Medicine, University Hospital of Sassari, Italy (5 patients). Antonella Vaccarino. UOSD di Ematologia e Malattie Trombotiche Ospedale San Giovanni Bosco - Torino (5 patients). Barbara Nardo. Department of Medicine I, Busto Arsizio Hospital, Italy (5 patients). Marcello Di Nisio. Department of Medical, Oral, and Biotechnological Sciences, University G. D Annunzio, Chieti, Italy (4 patients). Maria T. DeSancho. Hematology-Medical Oncology Division, Weill-Cornell Medical College (3 patients). Dominique Farge-Bancel, Cécile Durant. Unité dei Médecine Interne et Pathologie Vasculaire, Université Denis Diderot, Paris, France (1 patient). Asher Winder. Coagulation Unit, Wolfson Medical Center, Israel (1 patient). Elena Elli. Hematology Division, S. Gerardo Hospital, Monza, Italy (1 patient). Etienne Ciantar. Leeds General Infirmary, UK (1 patient) American Medical Association. All rights reserved. 3

4 efigure 1. Kaplan-Meier curves for the cumulative incidence of major bleeding events (A) and thrombotic events (B) in patients with hematological cancer (54 patients, including 49 with myeloproliferative neoplasms) and solid cancer Major bleeding events Hematological cancer Solid cancer 0.20 Cumulative incidence Follow-up (years) 0.25 Vascular thrombotic events Hematological cancer Solid cancer 0.20 Cumulative incidence Follow-up (years) 2015 American Medical Association. All rights reserved. 4

5 etable 1. Characteristics of Thrombotic Events Thrombotic events, n 68 Incidence rate of thrombotic events (95% CI) 7.3 ( ) per 100 pt-y Venous thrombotic events * o SVT, n 41 o Other site VTE (DVT and/or PE), n 13 Arterial thrombotic events * o Stroke or TIA, n 2 o Acute coronary syndrome, n 3 o Peripheral artery disease, n 1 Intestinal infarct, n 1 Vascular death, n 9 CI: confidence intervals; pt-y: patient-years; SVT: Splanchnic vein thrombosis; VTE: venous thromboembolism; DVT: deep vein thrombosis; PE: pulmonary embolism; TIA: transient ischemic attack *One patient had a concomitant diagnosis of an arterial and a venous thrombotic event, while another patient had a concomitant diagnosis of SVT and VTE in another site 12 thrombotic events occurred during vitamin K antagonists treatment: the INR was above the therapeutic range in 1 patient, within the therapeutic range in 5 patients, below the therapeutic range in 4 patients, and not available in 2 patients American Medical Association. All rights reserved. 5

6 etable 2. Multivariate Analysis for Major Bleeding Whole study cohort Liver cirrhosis with ascites Liver cirrhosis without ascites Ascites without liver cirrhosis Hazard Ratio % confidence interval p value < Patients without liver cirrhosis Anemia Patients with liver cirrhosis American Medical Association. All rights reserved. 6

7 etable 3. Multivariate Analysis for Thrombotic Events Whole study cohort Age (year) Male sex Hazard Ratio % confidence interval p value < Patients without liver cirrhosis Male sex Solid cancer Incidentally detected SVT Post-surgical SVT Myeloproliferative neoplasm Unprovoked SVT Patients with liver cirrhosis Male sex < SVT: Splanchnic vein thrombosis 2015 American Medical Association. All rights reserved. 7

8 etable 4. Tests of Interactions for Major Bleeding Events Interaction P value Cirrhosis Age Cirrhosis Male sex Cirrhosis Asian ethnicity Cirrhosis Personal History of VTE Cirrhosis Incidentally detected SVT Cirrhosis Gastrointestinal bleeding at onset Cirrhosis Ascites Cirrhosis Supra-hepatic vein thrombosis Non-computable Cirrhosis Unprovoked SVT Non-computable Cirrhosis Solid cancer Cirrhosis Myeloproliferative neoplasm Non-computable Cirrhosis Post-surgical SVT Cirrhosis Inflammatory bowel disease Non-computable Cirrhosis Anemia Cirrhosis Thrombocytopenia Cirrhosis Treatment duration VTE: Venous thromboembolism SVT: Splanchnic vein thrombosis 2015 American Medical Association. All rights reserved. 8

9 etable 5. Tests of Interactions for Thrombotic Events Interaction P value Cirrhosis Age Cirrhosis Male sex Cirrhosis Asian ethnicity Cirrhosis Personal History of VTE Cirrhosis Incidentally detected SVT Cirrhosis Gastrointestinal bleeding at onset Cirrhosis Ascites Cirrhosis Supra-hepatic vein thrombosis 1 Cirrhosis Unprovoked SVT Non-computable Cirrhosis Solid cancer Cirrhosis Myeloproliferative neoplasm Non-computable Cirrhosis Post-surgical SVT 1 Cirrhosis Inflammatory bowel disease Non-computable Cirrhosis Anemia Cirrhosis Thrombocytopenia Cirrhosis Treatment duration VTE: Venous thromboembolism SVT: Splanchnic vein thrombosis 2015 American Medical Association. All rights reserved. 9