Thrombotic and Hemorrhagic Complications after Surgery in Patients with Essential Thrombocythemia and Polycythemia Vera.
Authors: Ruggeri Marco , Rodeghiero Francesco , Tosetto Alberto , Castaman Giancarlo , Scognamiglio Francesca , Finazzi Guido , Delaini Federica , Micò Caterina , Vannucchi Alessandro M. , Antonioli Elisabetta , De Stefano Valerio , Zà Tommaso , Gugliotta Luigi , Tieghi Alessia , Mazzucconi Maria Gabriella , Santoro Cristina , Barbui Tiziano ,   the GIMEMA MPD Working Party
Published: October 2019

Abstract
Essential Thrombocythemia (ET) and Polycythemia Vera (PV) are chronic myeloproliferative diseases characterized by frequent episodes of deep venous thrombosis (DVT), arterial thromboembolism (AT) and by hemorrhagic complications. Surgical procedures could represent a risk factor for thrombosis and bleeding, but no data on the real frequency of these complications are available. To estimate the frequency of thrombosis and haemorrhages after surgical procedures and their outcomes, a multicenters retrospective analysis was performed. Data from 105 PV and 150 ET patients (128 males, 127 females, median age at diagnosis 60, were analyzed, for a total of 311 surgical interventions. At least one risk factor for arterial thrombosis (diabetes mellitus, hypercholesterolemia, arterial hypertension, previous AT, smoke) was present in 128/255 (50.1%), more frequently in PV than in ET patients (58.5 vs. 46.8%, p=0.02). An excess of male and older patients in PV than in ET explained this finding (multivariate analysis). Previous DVT was present in 9/255 patients (3.5%). After diagnosis, antiplatelet drugs were given to 211/255 patients (82.7%); cytoreductive treatments to 188/255 (74%), warfarin to 16/255 (6.2%); all PV patients were phlebotomized. In 25/311 surgeries (8.0%), an emergency procedure was performed; 195 surgeries were done under general anaesthesia; 21/91 abdominal interventions (23%) were performed under laparoscopy. Major surgeries were 160/311 (51.4%). Data about antithrombotic prophylaxis were available for 292/311 surgeries: in 126 (43.2%) low molecular heparin, in 38 (13%) unfractioned heparin, in 5 (1.7%) warfarin and in 123 no anticoagulant therapy was administered. In 45/123 (36.6%) patients without antithrombotic prophylaxis, antiplatelet therapy was administered before surgery. 189/255 (74%) were on cytoreductive therapy before surgery; for 9 surgical procedures, a short cycle of chemotherapy was administered before surgery. Clinical outcomes after surgery were recorded with a 3 months follow-up. No event was observed in 259/311 procedures (83.2%); there were 12 arterial and 12 venous thrombotic events, 23 major and 7 minor hemorrhages and 5 deaths. AT were more frequent in ET patients (5.3 vs. 1.5%, p=0.08) while venous events were more frequent in PV patients (7.7 vs. 1.1%, p=0.002). There was a strong risk gradient for AT associated with the presence of one or more arterial risk factors (OR for 4 or more risk factors: 40.9, p=0.003). Platelet count and hematocrit at surgery (median 477 x 109 /l and 42.6%, respectively) were not associated with either venous or arterial thrombosis. There was no correlation between bleeding episodes and type of diagnosis, use of antithrombotic prophylaxis and type of surgery. In conclusion, despite an active approach (cytoreduction and antithrombotic prophylaxis in the majority of the cases) a high proportion of PV and ET surgeries was complicated by DVT and AT (7.7%) but also by major hemorrhages (7.3%), requiring more investigation on the optimal prophylaxis in these patients.