A Prospective Cohort Study of Upper Extremity Deep Vein Thrombosis

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 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

Figure. Kaplan-Meier survival curve for VTE recurrence