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Ovarian Vein Thrombosis Is a Rare 2,8 , Paul R Original Research Ovarian Vein Thrombosis Incidence of Recurrent Venous Thromboembolism and Survival 08/29/2018 on BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD327SBzrFI0+nKTXy59vy3XxjnbOCDYUPQxSKWe9FqkYPnhp+DW18uqA== by https://journals.lww.com/greenjournal from Downloaded Charles J. Lenz, MD, Waldemar E. Wysokinski, MD, PhD, Stanislav Henkin, MD, Kevin P. Cohoon, DO, Ana Casanegra, MD, Benjamin S. Simmons, Rayya A. Saadiq, DO, Paul R. Daniels, MD, Downloaded Ewa M. Wysokinska, MD, Haraldur Bjarnason, MD, and Robert D. McBane, MD from https://journals.lww.com/greenjournal OBJECTIVE: To identify the risk of venous thromboem- tion (hazard ratio 6.7, P5.04 and hazard ratio 13.6, P5.03, bolism recurrence, major bleeding, and mortality in respectively). There was no significant difference in over- patients with ovarian vein thrombosis so as to better all survival. define optimal treatment strategies. CONCLUSION: Ovarian vein thrombosis is a rare METHODS: Patients with ovarian vein thrombosis thrombotic condition with an incidence 60-fold lower by (1990–2015) and age- and gender-matched patients with compared with leg DVT in our institution. The striking BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD327SBzrFI0+nKTXy59vy3XxjnbOCDYUPQxSKWe9FqkYPnhp+DW18uqA== contemporary leg deep vein thrombosis (DVT) were as- association with cancer adversely affects overall survival sessed for differences in etiology, venous thromboembo- rates in patients with ovarian vein thrombosis. Venous lism recurrence, and survival in a case–control study. thromboembolism recurrence rates argue for anticoagu- RESULTS: Over the timeframe of this study, only 219 lation with a direct oral anticoagulant or vitamin K ovarian vein thrombosis cases were identified compared antagonist, particularly in those with a history of venous with 13,417 leg DVTs. Median duration of follow-up was thromboembolism. 1.23 years (interquartile range 0.25–4.14). Pulmonary em- (Obstet Gynecol 2017;130:1127–35) bolism was identified at presentation in 6% of patients DOI: 10.1097/AOG.0000000000002319 with ovarian vein thrombosis and 16% of those with DVT P5 ( .001). Frequent causes of ovarian vein thrombosis varian vein thrombosis is an uncommon event included cancer, hormonal stimulation, surgery, and hos- Ohistorically attributed to either pelvic inflamma- pitalization. Cancer was twofold more frequent in pa- tory disease or the postpartum period. In recent years, tients with ovarian vein thrombosis (44% compared gynecologic surgery and pelvic malignancy have with 21%; P,.01). Despite being less frequently treated – emerged as important causative associations.1 4 Ovar- with anticoagulation (ovarian vein thrombosis 54% com- ian vein thrombosis is estimated to complicate 1 per pared with DVT 98%, P,.001), venous thromboembolism 600 to 1 per 2,000 pregnancies, typically in the post- recurrence rates were similar between groups (ovarian vein thrombosis 2.3 compared with DVT 1.8 per 100 partum period. The incidence has been reported to be 5,6 patient-years, P5.49). A personal history of venous as high as 0.18% of the general population, yet the thromboembolism and preceding surgery was found to natural history of ovarian vein thrombosis is not well be an independent risk factor for venous thromboembo- described including risk factors and recurrence rates. lism recurrence among those treated with anticoagula- Knowledge of these variables would be useful for the development of optimal treatment strategies. In the From the Gonda Vascular Center, Mayo Clinic, Rochester, Minnesota; and Duke absence of such data, there is little to guide clinicians on Medical Center, Durham, North Carolina. in the management of these patients. 08/29/2018 Each author has indicated that he or she has met the journal’s requirements for Anatomically, the ovarian vein represents a portion authorship. of the deep venous system with a direct connection to Corresponding author: Robert D. McBane, MD, Department of Cardiovascular theinferiorvenacavaontherightandtherenalveinon Medicine, Mayo Clinic and Foundation for Education and Research, 200 SW the left.7 Treatment with anticoagulation has been sug- First Street, Rochester, MN 55905; email: [email protected]. gested, but societal guidelines on the issue have not Financial Disclosure 2,8–12 The authors did not report any potential conflicts of interest. been published. Despite this, the risk of thrombus propagation, pulmonary embolism, and venous throm- © 2017 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved. boembolism recurrence remains poorly defined. ISSN: 0029-7844/17 Recent evidence suggests that the risk of recurrent VOL. 130, NO. 5, NOVEMBER 2017 OBSTETRICS & GYNECOLOGY 1127 Copyright ª by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. venous thromboembolism depends strongly on risk fac- same vascular territory was distinguished from the tors present at the time of the initial thrombotic event.2– original thrombus by comparing serial imaging 4,8 modalities.13,14 Major hemorrhage was defined as vis- Given the relative rarity of ovarian vein throm- ible bleeding and a fall in hemoglobin of 2 g/dL; bosis, it is unlikely that a randomized controlled trial hemorrhage requiring transfusion of two units of will be forthcoming. The objective of this study is to blood; or intraocular, intracerebral, or retroperitoneal identify the risk of venous thromboembolism recur- hemorrhage.13,14 rence, major bleeding, and mortality in patients with Hospitalizations, malignancy, hormonal stimula- ovarian vein thrombosis so as to better define optimal tion, trauma, infections, surgeries, or active inflam- treatment strategies. Outcomes were compared with matory disease were considered a positive risk factor a randomly selected group of female patients with if they occurred within the 3 months preceding the contemporary leg deep vein thrombosis (DVT). diagnosis of ovarian vein thrombosis. Hospitalizations included any overnight inpatient stay in a hospital. MATERIALS AND METHODS Malignancy included any active cancer or treatment A case–control study was conducted in which con- for cancer. Infection included any diagnosis of a bac- secutive patients with the diagnosis of ovarian vein terial infection that required treatment. This infection thrombosis evaluated at the Mayo Clinic between could have occurred anywhere in the body and was January 1, 1990, and October 22, 2015, were identi- further classified by organ system. Pelvic inflamma- fied using an electronic database search for “ovarian tory disease, pelvic abscess, urinary tract infections, vein thrombosis,”“gonadal vein thrombosis,” or and endometritis were considered genitourinary in- a similar variant in the text of an electronic note. Pa- fections. Trauma was considered a risk factor if an tients were confirmed by radiology report or by clear injury or trauma was severe enough as to require documentation in the electronic medical record of the medical or surgical treatment. Hormonal stimulation diagnosis including specific location. The control was considered a risk if a patient was on hormone group consisted of randomly selected female patients therapy, pregnant, or on oral contraceptive pills. diagnosed with leg DVT matched by age and diag- Surgeries were considered a risk if performed at any nosis date. Patients with ovarian vein thrombosis were location. Active inflammatory disease included any grouped by age (18–30, 30–40, 40–50, 50–60, 60–70, noninfectious inflammatory disease such as inflam- or older than 70 years) and diagnosis date (1990– matory bowel disease or an autoimmune condition. 1994, 1995–1999, 2000–2004, 2005–2009, or 2010– Thrombi were considered unprovoked if no risk 2015). All female patients with a diagnosis of DVT factors could be identified during this interval. within each diagnosis date group and age group were Differences between Kaplan-Meier curves were identified from an electronic database of patients seen determined using the two-sample log-rank test. Fisher at the Mayo Clinic. A random number generator was exact test was used to determine significance of then used to select a corresponding patient with DVT a difference in categorical variables. The Cox pro- for each patient with ovarian vein thrombosis from portional hazards model was used to assess variables among all patients with DVT identified in their cor- important in predicting survival and venous throm- responding age and diagnosis date group. Data were boembolism recurrence. Simultaneous CIs were used collected from a centralized electronic medical record when constructing 95% CIs on survival curves. that contains every inpatient hospitalization, out- Thrombotic distribution differences (right compared patient visit, radiology examination, laboratory re- with left, excluding bilateral) for patients with ovarian sults, pathology results (including autopsy reports), vein thrombosis and those with DVT was assessed death certificates, and relevant correspondence for all using the x2 test. Analysis was performed using JMP patients. The study was approved by the Mayo Clinic 10. institutional review board. Anticoagulation was defined as treatment of RESULTS thrombosis with a direct oral anticoagulant or vitamin Between January 1, 1990, and October 22, 2015, 219 K antagonist. A recurrent venous thromboembolism patients
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