Thromboembolic Events in Mesothelioma

Background. Thromboembolic event (TEE) rates in the general population and the cancer population are 0.1% to 2% and 10% to 15%, respectively. Our clinical observation is that mesothelioma patients are very susceptible to TEE, including arterial thromboses, but the TEE incidence has not been reported. This retrospective study attempts to determine the rates of TEE in patients with mesothelioma. Methods. Three hundred seventy-four patients with mesothelioma were identified through the New Mexico SEER database. Sixty-five of them were included in the University of New Mexico tumor registry from 1973 to 2003. Documented TEE rates were abstracted from the patient charts. Chi-square test, Fisher’s exact test, and logistic regression were used to identify potentially associated prognostic factors. Results. Fifty-four medical records were reviewed. Patients had a median of six visits (range, 1 to 63 visits). Median age was 60 years (range, 29 to 79 years). Sex distribution was 11 women and 43 men. Anatomic locations of the primary tumor were 35 pleural, 17 peritoneal, 1 pericardial, and 1 pericardial or pleural mesothelioma. The TEE rate was 27.7% (15 of 54), including 10 deep venous thromboses, 2 arterial clots, 2 myocardial infarctions, and 1 pulmonary embolus. No association between the development of TEE and any known prognostic factors were observed. Conclusions. The 27.7% TEE incidence rate in mesothelioma patients is higher than in other cancer patients. The true incidence of TEE in mesothelioma is likely to be higher than the rate observed in our review, owing to the retrospective nature of the data. Prophylactic anticoagulation trials are recommended to determine the prevention benefit in this high-risk population. (Ann Thorac Surg 2008;85:1032– 8) © 2008 by The Society of Thoracic Surgeons Mesothelioma is a rare type of cancer that arises from mesothelial cells within the pleura, the peritoneum, the pericardium, and the tunica vaginalis. The pleura is the most frequently diseased organ seen in about 80% of cases. The median survival of patients is generally short once mesothelioma is diagnosed; untreated and treated patients survive between 4 and 13 and 6 and 18 months, respectively [1, 2]. Thromboembolic events (TEE) are common in cancer patients [3, 4]. Such events include deep venous thrombosis (DVT), pulmonary embolism, and more rarely, but not infrequently, arterial thrombosis. The incidence of first episode of symptomatic TEE has been estimated to be 0.1% to 2% in the general population [5] and 10% to 15% in the cancer population [6]. About 40% of all patients with TEE develop clinical symptoms [7]. Pulmonary embolism often develops as a sequelae of DVT and accounts for 10% of all hospital deaths in nonmalignant patients, and death occurs in another 5% independent of diagnosis and treatment [8]. In patients who have developed TEE, the risk of developing cancer is increased in the first 6 months to 1 year, with a continued risk for up to 10 years [9]. A strong association between cancer and thrombosis has been documented in several large-scale retrospective studies [10]. One in every 7 hospitalized cancer patients dies secondary to pulmonary embolism [11]. A dual diagnosis of TEE and malignancy often is an indicator of a more aggressive cancer with a worse prognosis and decreased survival [11]. Ovarian, pancreatic, brain, and hepatic cancers induce a hypercoagulable state and are associated with a high incidence of TEE [12]. Mesothelioma cells secrete procoagulant factors and interleukin 6, which could enhance platelet function and thrombosis while promoting inhibition of fibrinolysis [13, 14]. Several studies have examined DVT prophylaxis in cancer patients, including the CLOT, FAMOUS, and MALT trials [15–17]. Data emerging from these large-scale studies have confirmed that a survival benefit is conferred from low-molecularweight heparin prophylaxis. Low-molecular-weight heparin in combination with chemotherapy may also improve outcomes secondary to an antineoplastic effect [18]. Our study attempts to determine the rate of TEE in patients with mesothelioma and to possibly correlate known prognostic factors with the development of TEE. Factors of poor prognosis in mesothelioma include site of origin, male sex, older age, and poor performance status. Other factors that have been reported to affect prognosis are leukocytosis, anemia, thrombocytosis, increased lactate dehydrogenase levels, nonepithelial histologic identification, chest pain, and fever [19, 20]. We have also included possibly