Abstract
Introduction. Upper extremity deep vein thrombosis (UEDVT) is a relatively uncommon event with potentially serious complications. Its optimal treatment and clinical outcomes are not well studied. The objective of our study was to assess the safety and efficacy of a standardized management protocol for UEDVT as well as its long term complications.
Patients and methods. We conducted a prospective cohort study at 5 Canadian centres and enrolled adult patients with a symptomatic UEDVT confirmed by compression ultrasound involving the brachial or more proximal veins, with or without a pulmonary embolism (PE). Exclusions included pregnancy, dialysis catheter thrombosis, active or high bleeding risk, platelet count <100x109/L, creatinine clearance < 30 ml/min, on warfarin for other indications, hemodynamically unstable PE, acute leukemia or undergoing a stem cell transplant within 3 months, geographical inaccessibility, life expectancy <3 months or treatment with low molecular weight heparin (LMWH) or warfarin for more than 7 days since diagnosis. Standardized treatment regimens were as follows: spontaneous or central venous catheter (CVC)-related UEDVT were treated with dalteparin at therapeutic doses for at least 5 days followed by warfarin adjusted according to INR results. Spontaneous UEDVT was treated for at least 6 months and CVC-related events were treated for at least 3 months or for as long as the line remained in place and for at least 1 month after line removal. Cancer patients with non CVC-related UEDVT were treated using dalteparin alone for a minimum of 6 months. Main outcomes were objectively documented venous thromboembolism (VTE) recurrence, major bleeding and death. All outcomes were centrally adjudicated. Patients were followed for 2 years. Data was analyzed using descriptive statistics. Survival data was analyzed using the Kaplan-Meier Method. Post-hoc analyses were conducted comparing CVC and spontaneous events. The study was approved by all institutional review boards.
Results. Between 2009 and 2012, we enrolled 141 patients: 75 with spontaneous and 66 with CVC related UEDVT. Mean age was 51 years; 55% were males. The population characteristics are shown in the Table. The 2 year cumulative incidence of VTE recurrence was 3.5% (95% CI 1.5-8), of major bleeding was 2.8% (95% CI 1.1-7.1) and of death was 22% (95% CI 16-29.5). VTE recurrence rate was no different for spontaneous vs. CVC-related groups (4% vs. 3%; Log-Rank P = 0.690; Figure).
Conclusion. The use of a standardized management protocol for patients with UEDVT results in a low risk of VTE recurrence and major bleeding at 2 years of follow up, in both CVC-related and spontaneous UEDVT.
Population characteristics
| Spontaneous UEDVT | Catheter-related UEDVT | Total | P-value | ||||
|---|---|---|---|---|---|---|---|
| N | % | N | % | N | % | ||
| Demographics | |||||||
| Age (Mean [SD]) | 48.6 | [17.8] | 54.9 | [13.6] | 51.6 | [16.2] | NS |
| Male gender | 44 | 58.7 | 34 | 51.5 | 78 | 55.3 | NS |
| Caucasian | 67 | 89.3 | 64 | 97.0 | 131 | 92.9 | NS |
| Comorbidities | |||||||
| Previous VTE | 3 | 4.0 | 2 | 3.0 | 5 | 3.5 | NS |
| Prior or concurrent cancer | 22 | 29.3 | 48 | 72.7 | 70 | 49.6 | <0.001 |
| Prior gastrointestinal Bleeding | 6 | 8.0 | 5 | 7.6 | 11 | 7.8 | NS |
| Type of Catheter | NE | ||||||
| Hickman | - | - | 1 | 1.5 | 1 | 0.7 | |
| PICC | - | - | 49 | 74.2 | 49 | 34.8 | |
| Porta Cath | - | - | 16 | 24.2 | 16 | 11.3 | |
| Thrombus Location | |||||||
| Subclavian | 54 | 72.0 | 43 | 65.2 | 97 | 68.8 | NS |
| Superior vena cava | 0 | 0.0 | 2 | 3.0 | 2 | 1.4 | NS |
| Brachiocephalic | 5 | 6.7 | 10 | 15.2 | 15 | 10.6 | NS |
| Internal Jugular | 16 | 21.3 | 14 | 21.2 | 30 | 21.3 | NS |
| Axillary | 39 | 52.0 | 34 | 51.5 | 73 | 51.8 | NS |
| External Jugular | 1 | 1.3 | 2 | 3.0 | 3 | 2.1 | NS |
| Treatment Duration | |||||||
| 3 Months | 26 | 34.7 | 19 | 28.8 | 45 | 31.9 | <0.001 |
| 6 Months | 37 | 49.3 | 4 | 6.1 | 41 | 29.1 | 0.000 |
| Other | 12 | 16.0 | 43 | 65.2 | 55 | 39.0 | 0.000 |
| Spontaneous UEDVT | Catheter-related UEDVT | Total | P-value | ||||
|---|---|---|---|---|---|---|---|
| N | % | N | % | N | % | ||
| Demographics | |||||||
| Age (Mean [SD]) | 48.6 | [17.8] | 54.9 | [13.6] | 51.6 | [16.2] | NS |
| Male gender | 44 | 58.7 | 34 | 51.5 | 78 | 55.3 | NS |
| Caucasian | 67 | 89.3 | 64 | 97.0 | 131 | 92.9 | NS |
| Comorbidities | |||||||
| Previous VTE | 3 | 4.0 | 2 | 3.0 | 5 | 3.5 | NS |
| Prior or concurrent cancer | 22 | 29.3 | 48 | 72.7 | 70 | 49.6 | <0.001 |
| Prior gastrointestinal Bleeding | 6 | 8.0 | 5 | 7.6 | 11 | 7.8 | NS |
| Type of Catheter | NE | ||||||
| Hickman | - | - | 1 | 1.5 | 1 | 0.7 | |
| PICC | - | - | 49 | 74.2 | 49 | 34.8 | |
| Porta Cath | - | - | 16 | 24.2 | 16 | 11.3 | |
| Thrombus Location | |||||||
| Subclavian | 54 | 72.0 | 43 | 65.2 | 97 | 68.8 | NS |
| Superior vena cava | 0 | 0.0 | 2 | 3.0 | 2 | 1.4 | NS |
| Brachiocephalic | 5 | 6.7 | 10 | 15.2 | 15 | 10.6 | NS |
| Internal Jugular | 16 | 21.3 | 14 | 21.2 | 30 | 21.3 | NS |
| Axillary | 39 | 52.0 | 34 | 51.5 | 73 | 51.8 | NS |
| External Jugular | 1 | 1.3 | 2 | 3.0 | 3 | 2.1 | NS |
| Treatment Duration | |||||||
| 3 Months | 26 | 34.7 | 19 | 28.8 | 45 | 31.9 | <0.001 |
| 6 Months | 37 | 49.3 | 4 | 6.1 | 41 | 29.1 | 0.000 |
| Other | 12 | 16.0 | 43 | 65.2 | 55 | 39.0 | 0.000 |
Kaplan-Meier survival curve for VTE recurrence
Lazo-Langner:Bayer: Honoraria; Pfizer: Honoraria. Wells:Bayer: Honoraria; BMS/Pfizer: Research Funding. Carrier:BMS: Research Funding; Bayer: Consultancy; Pfizer: Consultancy; LEO Pharma: Consultancy, Research Funding. Kovacs:Bayer: Honoraria, Research Funding; LEO Pharma: Honoraria; Daiichi Sankyo Pharma: Research Funding; Pfizer: Honoraria, Research Funding.
