UEVT is a well-recognized complication of PICCs, and in patients without cancer, asymptomatic UEVT has been detected in 37% to 66%.1,6,10
This retrospective study is the first to our knowledge to determine the incidence of symptomatic UEVT in patients with cancer and identify the risk factors specifically associated with PICC-related UEVT in this population. Although previous studies have identified PICC-specific qualities that increase UEVT risk, this study also evaluated patient-specific risk factors. In the present study, 36 (15%) of 237 patients with cancer developed symptomatic UEVT. The incidence of 15% is somewhat higher than that in previous studies, which have reported rates of 2% to 7.8%.8,11–15
In addition, the infection rate in this study (13.9%) is higher than the 2.46% to 13.04% reported in previous studies.3,5,11,14
This was seen despite the fact that evidence-based infection-prevention strategies were performed with every PICC insertion, which entailed using appropriate sterile conditions and follow-up care.3,16–18
The higher observed rate of both UEVT and infection may be related to the number of days spent with a PICC inserted, because there was no institutional standard for the duration of PICC placement. Our results showed a median time of 50 days from the day of line insertion to infection. However, we did not examine the duration of PICC placement in those without symptomatic UEVT. Further investigation would be needed to determine the association between PICC placement duration and time to infection. Additionally, we did not examine length of hospitalization or admission diagnosis to determine if either of these variables had a significant impact on the rate of UEVT.
This analysis identified three baseline risk factors (hospitalization at time of PICC placement, infection, and use of ESAs) that predicted for development of symptomatic UEVT as well as one that showed a protective effect. Hospitalization and infection are well-established risk factors for thrombosis.19,20
The present results, showing an OR of 2.38 for hospitalization and UEVT, confirm the rate of PICC-associated thrombosis from previous studies.21–23
Of note, this study is the first to our knowledge to identify that concurrent use of ESAs significantly increased the risk for PICC-associated UEVT. This further adds to the body of literature suggesting a link between ESA use in patients with cancer and negative outcomes including thrombosis, which ultimately led the US Food and Drug Administration to restrict the use of these agents in those with cancer. Somewhat paradoxically, this analysis also demonstrated a statistically significant association between the use therapeutic anticoagulation at the time of PICC placement and UEVT. Although the precise explanation for this observation is not clear, it is possible that this group of patients is at higher risk of additional thrombotic events despite attempted therapeutic anticoagulation. A majority of these patients were receiving warfarin, and we did not attempt to ascertain whether these patients were at therapeutic dosing of anticoagulation at the time of PICC insertion or throughout the duration of placement. Results from our analysis also identified that patients receiving APAs had a lower rate of PICC-associated UEVT (OR, 0.25; 95% CI, 0.07 to 0.92; P
= .04). APAs have been well documented to protect against arterial and venous thrombosis in specific settings, but their role as antithrombotic agents in CVCs has not.
There are several limitations with our study. This was a retrospective single-center study, so the results may not be applicable to other institutions, especially if the type of catheter used and protocol for catheter maintenance and care differ from those in our institution. The present cohort consisted of predominately white male patients who received care in the VA system. As a result, the application of these results to the general population is uncertain. Furthermore, the true incidence of UEVT is likely higher, because the diagnosis of UEVT via ultrasound is less sensitive in the upper than in the lower extremity.24
Additionally, UEVT was only recorded in those patients who were symptomatic; early UEVT may not have detected. Last, the relationship between specific cancer type and primary site was not examined; because of our sample size, it would not have been significant. In addition, with the exceptions of capecitabine/FU and bevacizumab, we did not consider other potentially prothrombotic chemotherapy agents such as lenalidomide and thalidomide because their use was limited in our cohort of patients with PICCs.
In conclusion, our study identified several patient characteristics that may predispose those with cancer to PICC-associated UEVT. Specifically, at the time of PICC insertion, patients with active infections, hospitalized patients, patients receiving ESAs, and patients receiving TDA had a significantly increased risk of UEVT, whereas the use of APAs had a protective effect against UEVT. Future prospective studies are required to better define the significant risk factors for PICC-associated UEVT in this population and may then allow the development of risk stratification models for development of UEVT. Currently, there is a lack of consistent evidence on the efficacy of thrombosis prophylaxis in patients with cancer.25
Our results suggest that the use of APAs is one prophylactic strategy that could be further evaluated in those patients with cancer felt to be at high risk for the development of PICC-associated UEVT.