Management of Cancer-Associated Upper Extremity Deep Vein Thrombosis with and without Venous Catheters at a Tertiary Care Center

Introduction: Data on management of upper extremity deep vein thrombosis(UEDVT) in patients with cancer is limited. Patients in this subgroup were excluded from the large clinical trials that showed the efficacy of extended duration low-molecular-weight heparin (LMWH) for cancer-associated thrombosis. Furthermore, risk factors for cancer-associated UEDVT in patients who do not have central lines in situ have not been well defined. The goal of our study was to determine the risk factors for cancer-associated UEDVT and to examine the approach to management of these patients in a real-world setting.

Methods: We conducted a retrospective review of 200 consecutive patients who were assessed for cancer-associated UEDVT between January 2010 and June 2014 at a tertiary care center. Outcome measures were recurrent VTE, and major and clinically relevant non-major bleeding. Risk factors for recurrent VTE and bleeding were assessed using multivariable analysis. 

Results: Median duration of follow-up 11 months. Median age was 61.5 years and 55% were male. Cancer subtypes included colorectal (24%), lung (15%), breast (14%), lymphoma (10%), leukemia (5%), esophageal (4%), pancreatic (4%), head & neck (3%), sarcoma (2%), and others 17%. Metastatic disease at the time of diagnosis was present in 37% of patients and 7% of the study population had a previous history of VTE. Of the study population, 138 (69%) had line-associated UEDVT. Risk factors for UEDVT other than presence of a line after univariate analysis were lung cancer, breast cancer and extrinsic compression of vessels by local tumour on diagnostic imaging.

The proportion of patients with UEDVT in the absence of a line according to cancer subtype was as follows: lung cancer (83%), pleural mesothelioma (66%), breast cancer (51%) and head & neck cancer (50%). Of these patients, greater than half had evidence of local mass effect on vessels on diagnostic imaging studies. Of the 138 patients with line-associated UEDVT, 20 (15%) had their line removed within one week of diagnosis for reasons unrelated to thrombosis and 107 (84%) had their line removed after completion of at least 3 months of anticoagulant therapy.

Recurrent VTE was documented in 35 patients (17.5%), of which 16 (8%) were UEDVT (PE – 10, lower limb DVT-8, other-2). Recurrent VTE while receiving anticoagulants occurred in 23 (65.7%) of all recurrences and in 10 (62.5%)of UEDVT recurrences. Recurrent VTE occurred in 26 patients with a central line and in 9 patients without a central line. All of the patients with recurrent VTE had solid tumours, and 45% had metastatic disease. Multivariant analysis revealed that male gender(OR 2.42, 95% CI;1.1-5.1,p-value=0.02) and active cancer at the end of follow-up (OR 2.47, 95% CI; 0.1-0.9, p-value=0.04) were the only factors significantly associated with recurrent VTE (Figure 1 and 2). None of the following were significant risk factors for recurrence: type of antineoplastic treatment, accompanying PE, white cell count, initial UEDVT while anticoagulated, cancer stage, previous VTE, number of involved venous segments, removal of line during first week after index event or switching to a different anticoagulant. In the group with UEDVT without a venous catheter, the presence of radiologically proven extrinsic compression of vessels was not statistically associated with recurrent VTE.

Patients were treated with LMWH for a median duration of 5 months. Six and 8 patients were switched to rivaroxaban and warfarin, respectively. Clinically relevant non-major bleeding occurred in 24 patients (12%), 61% of the bleeds were gastrointestinal and 83% of the bleeds occurred while receiving anticoagulants. On multivariate analysis, bleeding was significantly associated with ongoing anticoagulation (OR 5.6, 95% CI;1.6-19.3, p-value=0.006) and liver metastasis (OR 7.2, 95% CI;0.9-7.2,p-value=0.05).The use of concomitant clopidogrel or aspirin significantly increased the risk of bleeding (OR 6.6 and 5.5, respectively).

Conclusions: While the presence of a venous catheter was the primary risk factor for UEDVT for the majority of our cohort, extrinsic compression of vessels by local tumour appeared to be equally important for certain cancer types. Furthermore, our finding that the majority of recurrent events did not occur in the upper limb suggests that UEDVT may be predictive of overall increased thrombogenic risk rather than just a local effect caused by the line.