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.

Table 1.

Population characteristics

Spontaneous UEDVTCatheter-related UEDVTTotalP-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 UEDVTCatheter-related UEDVTTotalP-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 
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Figure 1.
Figure 1. Kaplan-Meier survival curve for VTE recurrence
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Kaplan-Meier survival curve for VTE recurrence

Figure 1.
Figure 1. Kaplan-Meier survival curve for VTE recurrence
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Kaplan-Meier survival curve for VTE recurrence

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Disclosures

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.

Topics:
deep venous thrombosis of upper extremity, prospective studies, central venous catheters, venous thromboembolism, hemorrhage, warfarin, cancer, catheters, dalteparin, low-molecular-weight heparin

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2015 by The American Society of Hematology
2015
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