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Original Research: ANTITHROMBOTIC THERAPY |

Clinical Outcome of Patients With Upper-Extremity Deep Vein Thrombosis*: Results From the RIETE Registry FREE TO VIEW

Francisco José Muñoz, MD, PhD; Patrick Mismetti, MD; Renzo Poggio, MD; Reina Valle, MD; Manuel Barrón, MD; María Guil, MD; Manuel Monreal, MD, PhD; for the RIETE Investigators
Author and Funding Information

Affiliations: *From the Department of Internal Medicine (Dr. Muñoz), Hospital de Mollet, Mollet del Vallès, Barcelona, Spain; Department of Internal Medicine (Dr. Mismetti), Hospital Bellevue, Saint-Etienne, France; Internal Medicine Thrombosis Center (Dr. Poggio), Hospital Galliera, Genoa, Italy; Department of Internal Medicine (Dr. Valle), Hospital Sierrallana, Torrelavega, Cantabria, Spain; Department of Pneumology (Dr. Barrón), Complejo Hospitalario San Millán y San Pedro, Logroño, La Rioja, Spain; Department of Internal Medicine (Dr. Guil), Hospital de la Axarquía, Vélez, Málaga, Spain; and Department of Internal Medicine (Dr. Monreal), Hospital Germans Trias i Pujol, Barcelona, Spain.,  A full list of RIETE investigators is given in the Appendix.

Correspondence to: Manuel Monreal, MD, PhD, Professor of Medicine. Serviicio de Medicina Interna, Hospital Universitari Germans Trias i Pujol, 08916 Badalona, Spain; e-mail: mmonreal.germanstrias@gencat.net


Affiliations: *From the Department of Internal Medicine (Dr. Muñoz), Hospital de Mollet, Mollet del Vallès, Barcelona, Spain; Department of Internal Medicine (Dr. Mismetti), Hospital Bellevue, Saint-Etienne, France; Internal Medicine Thrombosis Center (Dr. Poggio), Hospital Galliera, Genoa, Italy; Department of Internal Medicine (Dr. Valle), Hospital Sierrallana, Torrelavega, Cantabria, Spain; Department of Pneumology (Dr. Barrón), Complejo Hospitalario San Millán y San Pedro, Logroño, La Rioja, Spain; Department of Internal Medicine (Dr. Guil), Hospital de la Axarquía, Vélez, Málaga, Spain; and Department of Internal Medicine (Dr. Monreal), Hospital Germans Trias i Pujol, Barcelona, Spain.,  A full list of RIETE investigators is given in the Appendix.


Chest. 2008;133(1):143-148. doi:10.1378/chest.07-1432
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Published online

Background: There is little information on the clinical outcome of patients with upper-extremity deep vein thrombosis (DVT).

Methods: RIETE is an ongoing registry of consecutive patients with objectively confirmed, symptomatic, acute DVT or pulmonary embolism (PE). In this analysis, we analyzed the demographic characteristics, treatment, and 3-month outcome of all patients with DVT in the arm.

Results: Of the 11,564 DVT patients enrolled, 512 patients (4.4%) had arm DVT. They presented less often with clinically overt PE (9.0% vs 29%; odds ratio, 0.24; 95% confidence interval [CI], 0.18 to 0.33) than those with lower-limb DVT, but their 3-month outcome was similar. Of the 512 patients with arm DVT, 196 patients (38%) had cancer and 228 patients (45%) had catheter-related DVT. During follow-up, those with cancer DVT had an increased incidence of major bleeding (4.1% vs 0.9%; odds ratio, 4.4; 95% CI, 1.2 to 21), recurrent venous thromboembolism (6.1% vs 2.8%; odds ratio, 2.2; 95% CI, 0.91 to 5.6; p = 0.04), and death (22% vs 3.5%; odds ratio, 7.8; 95% CI, 4.0 to 16). Thirty patients had the composite event of recurrent DVT, symptomatic PE, or major bleeding. They were significantly older, more often had cancer, and presented more frequently with symptomatic PE on hospital admission. On multivariate analysis, only cancer patients with arm DVT had an increased risk for the composite event (odds ratio, 3.0; 95% CI, 1.4 to 6.4).

Conclusions: At presentation, patients with arm DVT have less often clinically overt PE than those with lower-limb DVT, but their 3-month outcome is similar. Among patients with arm DVT, those with cancer have the worse outcome.

Upper-extremity deep vein thrombosis (DVT) is an infrequent condition, originally considered benign and self-limited.110 When DVT in the arm is confirmed, anticoagulant therapy is the treatment of choice, but there is no consensus on their optimal management because only few patients with arm DVT have been included in clinical trials of anticoagulant therapy, and no prospective, comparative studies have been performed in this specific field.

The RIETE initiative is an ongoing, international (Spain, France, Italy, Israel, Argentina), multicenter, prospective registry of consecutive patients presenting with symptomatic, acute DVT or pulmonary embolism (PE) confirmed by objective tests.1115 The aim of the present study was to analyze the clinical characteristics, treatment options, and 3-month outcome in all patients with arm DVT.

Patient Entry Criteria

Consecutive patients with symptomatic, acute DVT or PE confirmed by objective tests (contrast venography or ultrasonography for suspected DVT, pulmonary angiography, lung scintigraphy, or helical CT scan for suspected PE) are enrolled in RIETE. Patients are excluded if they are currently participating in a therapeutic clinical trial or if they will not be available for a 3-month follow-up. All patients provided oral consent to their participation in the registry, according to the requirements of the ethics committee within each hospital.

Study End Point

The major outcome was the development of symptomatic, objectively confirmed PE, recurrent DVT, or major bleeding, within 90 days of therapy. All patients were followed up for at least 3 months after hospital discharge. During each visit, any signs or symptoms suggesting recurrences of DVT or PE, or bleeding complications were noted. Each episode of clinically suspected recurrent DVT or PE was documented by repeat compression ultrasonography, venography, lung scanning, helical CT scan, or pulmonary angiography. Bleeding complications were classified as “major” if they were overt and required a blood transfusion ≥ 2 U, or were retroperitoneal, spinal, or intracranial.

Variables

The parameters recorded by the registry include details of each patient’s baseline characteristics, risk factors for DVT, clinical characteristics of the thromboembolic event, treatment received on diagnosis, and main clinical outcomes such as bleeding, recurrent DVT or PE, and death. Patients were managed according to the clinical practice of each participating hospital and were not subject to any predetermined intervention.

Clinical Definitions

Immobilized patients are defined in this analysis as nonsurgical patients who had been immobilized (ie, total bed rest with bathroom privileges) for ≥ 4 days in the 2-month period prior to venous thromboembolism (VTE) diagnosis. Surgical patients were defined as those who had undergone an operation in the 2 months prior to diagnosis. Fatal PE was defined as any death occurring shortly after PE diagnosis (either the initial episode or recurrent PE), in the absence of an alternative cause of death. Bleeding complications were classified as “major” if they were overt and required a blood transfusion ≥ 2 U, or were retroperitoneal, spinal, or intracranial.

Data Collection

Study outcomes were adjudicated by the attending physicians, and data were recorded on to a computer-based case report form at each participating hospital and submitted to a centralized coordinating center through a secure Web site. Data quality was regularly monitored electronically to detect inconsistencies or errors, and by periodic visits to participating hospitals by contract research organizations, which compared the medical records with the data on the Web site. A full data audit was performed at periodic intervals.

Statistical Analysis

A commercial software package (SPSS version 12.0; SPSS; Chicago, IL) was used to calculate odds ratios and corresponding 95% confidence intervals (CIs), and a p value < 0.05 was considered statistically significant. The predictive value of selected variables for the composite event of symptomatic, objectively confirmed PE, recurrent DVT, or major bleeding during the first 3 months of therapy was evaluated by logistic regression. Candidate variables were based on published literature. Multivariate logistic analysis was performed to identify independent predictors of the composite event after adjustment for interactions between variables.

Study Support

The RIETE registry is an independent registry partially supported by Sanofi-Aventis in Spain and Red Respira from the Instituto Carlos III, Spain (Red Respira-ISCiii-RTIC-03/11). Sanofi-Aventis has no right to accede to the database, and there is no payment per recruited patient.

As of September 2006, 11,564 consecutive patients with symptomatic, acute DVT were enrolled at 124 participating centers. Of these, 512 patients (4.4%) had arm DVT. Patients with arm DVT were more often male, younger, and weighed less than those with lower-limb DVT (Table 1 ). They had less frequently recent immobility or prior VTE, but cancer was more common. Only 46 patients (9.0%) with arm DVT had clinically overt PE at presentation, compared to 29% of those with lower-limb DVT. During the 3-month study period, there were no differences among groups in the incidence of major or fatal bleeding, recurrent DVT, recurrent PE, or fatal PE (Table 1), but those with arm DVT had a higher mortality rate. Interestingly, although at baseline the percentage of patients with clinically overt PE was fourfold lower among those with arm DVT, the incidence of new PEs during follow-up was similar.

Of the 512 patients with arm DVT, 196 patients (38%) had cancer and 228 patients (45%) had catheter-related DVT (Table 2 ). The most common sites of cancer were the lung (28%), breast (15%), or colorectal (13%). The most frequent catheters were central lines (49%), port systems (22%), peripheral lines (14%), or pacemakers (11%). Catheter-related DVT was significantly more common in patients with cancer (53% vs 39%; odds ratio, 1.7; 95% CI, 1.2 to 2.5). Most patients (91%) were initially treated with low-molecular-weight heparin (LMWH). As for long-term therapy, 75% of patients with cancer received LMWH, while 76% of those with no cancer switched to oral anti-vitamin K drugs.

Among patients with arm DVT, bilateral DVT was significantly more common in those with cancer (7.7% vs 1.6%; odds ratio, 5.1; 95% CI, 1.9 to 16.0), while the presence of with clinically overt PE at presentation was similar (10% vs 8.2%). As for 3-month outcomes, cancer patients with arm DVT had an increased incidence of major bleeding (4.1% vs 0.9%; odds ratio, 4.4; 95% CI, 1.2 to 21), recurrent VTE (6.1% vs 2.8%; odds ratio, 2.2; 95% CI, 0.91 to 5.6; p = 0.04), and death (22% vs 3.5%; odds ratio, 7.8; 95% CI, 4.0 to 16). Two cancer patients with arm DVT had major bleeding and recurrent VTE: one patient bled shortly after increasing the LMWH doses for recurrent DVT, and one patient presented with recurrent PE after discontinuing coumarin due to GI bleeding.

Thirty patients had the composite event (recurrent DVT, symptomatic PE, or major bleeding) during the 3-month study period. They were significantly older, more often had cancer, and presented more frequently with clinically overt PE on hospital admission, as shown in Table 3 . Multivariate analysis confirmed that only cancer patients with arm DVT had an increased risk for the composite event (odds ratio, 3.0; 95% CI, 1.4 to 6.4).

The findings from this analysis, obtained from a large prospective series of consecutive patients in the RIETE registry, reveal the existence of significant differences in clinical characteristics and underlying diseases between patients with upper-limb or lower-limb DVT. However, despite the lower incidence of clinically overt PE in patients with arm DVT at baseline, their incidence of symptomatic PE, recurrent DVT, or major bleeding complications during the study period was similar. These findings have important implications for the targeting of arm DVT prophylaxis and therapy. In a recent retrospective study, Spencer et al16also found similar rates of recurrent DVT between patients with upper-limb vs lower-limb DVT. However, only 56% of their patients with arm DVT were prescribed warfarin at hospital discharge. Since the guidelines from the American College of Chest Physicians suggest that arm DVT should be treated similarly to lower-limb DVT,17 these data suggest a perception among clinicians that arm DVT does not require long-term anticoagulant therapy.

Because of the relative rarity of the disease, only studies with small sample sizes are available so far and, therefore, knowledge on the clinical outcome of patients with arm DVT is very limited. The largest series8 published so far included 592 patients with arm DVT but had no data on outcomes. Without accurate information on the clinical history of arm DVT, it is difficult to determine the need for thromboprophylaxis or the benefits of therapy.

Interestingly, the outcome in patients with arm DVT largely varies according to the presence or absence of cancer. Cancer patients with arm DVT had the worse prognosis, with a 9.7% incidence (19 of 196 patients) of recurrent DVT, symptomatic PE, or major bleeding during the study period. This is not unexpected because it is largely known that cancer patients with lower-limb DVT also have an increased incidence of VTE recurrences and bleeding.18Hence, measures for preventing arm DVT in patients with cancer should be considered as a first-line aim for the oncologists, although trials1921 have ailed to demonstrated any benefit in these patients. On the other side, those with no cancer or catheter had the better outcome, with only 0.5% (1 of 192 patients) having symptomatic PE, and no major bleeding.

The main limitation of our study lies on its design. In contrast to randomized controlled trials, no experimental intervention is imposed in RIETE; treatment is determined entirely by the treating physicians. Although this limits the nature of the conclusions that can be drawn, data captured and reported in the registry reflect “real-world” practices and outcomes in the treatment of VTE. Besides, selection bias was avoided by including consecutive patients with objectively confirmed, symptomatic, arm DVT who were referred to study centers. Another limitation lies on the likely underestimated incidence rate of fatal PE. Certainly, the death of some patients may have been due to PE, but these would not have been included because the Adjudication Committee only accepts VTE events that have been objectively confirmed. In any case, data from the registry are hypothesis generating and provide feedback from real-world clinical situations that may be of value when designing new randomized clinical studies.

In summary, although at presentation patients with arm DVT have less often clinically overt PE than those with lower-limb DVT, their 3-month clinical outcome is similar. These findings suggest that their appropriate therapy (drug, intensity, duration) should not differ.

Members of the RIETE Group include the following: Spain: Arcelus JI, Barba R, Blanco A, Barrón M, Bugés J, Casado I, Cisneros E, Conget F, Del Molino F, Del Toro J, Epelde F, Falgá C, Fernández-Capitán C, Font Ll, Gabriel F, Gallego P, García-Bragado F, Guijarro R, Guil M, Gutiérrez J, Gutiérrez MR, Hernández L, Jiménez D, Lecumberri R, López F, López L, López I, Maestre A, Martín-Villasclaras JJ, Monreal M, Muñoz FJ, Naufall MD, Nieto JA, Núñez MJ, Orue MT, Otero R, Portillo J, Rabuñal R, Román P, Ruiz-Giménez N, Sahuquillo JC, Samperiz AL, Sánchez JF, Sánchez R, Soler S, Soto MJ, Tiberio G, Todolí JA, Tolosa C, Trujillo J, Uresandi F, Valdés M, Valdés V, Valle R, and Vela J; France: Mismetti P, Rivron-Guillot K; Italy: Di Micco P, Enea I, Moretti V, Poggio R, Quintavalla R, Tiraferri E, Visonà A.

Abbreviations: CI = confidence interval; DVT = deep vein thrombosis; LMWH = low-molecular-weight heparin; PE = pulmonary embolism; VTE = venous thromboembolism

This study was supported by an unrestricted educational grant from Sanofi-Aventis, and by logistic and administrative support from the Registry Coordinating Center, S & H Medical Science Service.

The project was partially supported by Red Respira, Instituto Carlos III (RedRespira-ISCiii-RTIC-03/11).

The authors have no conflicts of interest to disclose.

Table Graphic Jump Location
Table 1. Clinical Characteristics and 3-Month Outcomes of the 11,564 DVT Patients According to the Location of DVT*
* 

Data are presented as No. (%) or mean ± SD unless otherwise indicated. NS = not significant.

Table Graphic Jump Location
Table 2. Three-Month Outcomes in 512 Patients With Arm DVT According to the Existence of Cancer and/or Catheter*
* 

Data are presented as No. (%) or mean ± SD unless otherwise indicated.

Table Graphic Jump Location
Table 3. Univariate Analysis on the Risk for Recurrent VTE or Major Bleeding in the 512 Patients With Arm DVT*
* 

Data are presented as No. (%) unless otherwise indicated. See Table 1 for expansion of abbreviation.

 

Two patients had major bleeding and recurrent VTE.

Tilney, NL, Griffiths, HJG, Edwards, EA (1970) Natural history of major venous thrombosis of the upper extremity.Arch Surg101,792-796. [PubMed] [CrossRef]
 
Prescott, SM, Tikoff, G Deep venous thrombosis of the upper extremity: a reappraisal.Circulation1979;59,350-355. [PubMed]
 
Demeter, SL, Pritchard, JS, Piedad, OH, et al Upper extremity thrombosis: etiology and prognosis.Angiology1982;33,743-755. [PubMed]
 
Davis, G, Kaplan, K, Kwaan, HC Pulmonary emboli from a platelet-rich thrombus attached to a pacemaker electrode.Pace1983;6,883-886. [PubMed]
 
Anderson, AJ, Krasnow, SH, Boyer, MW, et al Thrombosis: the major Hickman catheter complication in patients with solid tumor.Chest1989;95,71-75. [PubMed]
 
Becker, DM, Philbrick, JT, Walker, FB Axillary and subclavian venous thrombosis: prognosis and treatment.Arch Intern Med1991;151,1934-1943. [PubMed]
 
Lee, AYY, Levine, MN, Butler, G, et al Incidence, risk factors, and outcomes of catheter-related thrombosis in adult patients with cancer.J Clin Oncol2006;24,1404-1408. [PubMed]
 
Joffe, HV, Kucher, N, Tapson, VF, et al Upper-extremity deep vein thrombosis: a prospective registry of 592 patients.Circulation2004;110,1605-1611. [PubMed]
 
Prandoni, P, Bernardi, E, Marchiori, A, et al The long term clinical course of acute deep vein thrombosis of the arm: prospective cohort study.BMJ2004;329,484-485. [PubMed]
 
Martinelli, I, Battaglioni, T, Bucciarelli, P, et al Risk factors and recurrence rate of primary deep vein thrombosis of the upper extremities.Circulation2004;110,566-570. [PubMed]
 
Monreal, M, Falgá, C, Valdés, M, et al Fatal pulmonary embolism and fatal bleeding in cancer patients with venous thromboembolism: findings from the RIETE registry.J Thromb Haemost2006;4,1950-1956. [PubMed]
 
Trujillo-Santos, J, Herrera, S, Page, MA, et al Predicting adverse outcome in outpatients with acute deep vein thrombosis: findings from the RIETE Registry.J Vasc Surg2006;44,789-793. [PubMed]
 
López-Jiménez, L, Montero, M, González-Fajardo, JA, et al Venous thromboembolism in very elderly patients: findings from a prospective registry (RIETE).Haematologica2006;96,1046-1051
 
Nieto, JA, Bruscas, MJ, Ruiz-Ribo, D, et al Acute venous thromboembolism in patients with recent major bleeding: the influence of the site of bleeding and the time elapsed on outcome.J Thromb Haemost2006;4,2367-2372. [PubMed]
 
Monreal, M, Falgá, C, Valle, R, et al Venous thromboembolism in patients with renal insufficiency: findings from the RIETE Registry.Am J Med2006;119,1073-1079. [PubMed]
 
Spencer, FA, Emery, C, Lessard, D, et al Upper extremity deep vein thrombosis: a community-based perspective.Am J Med2007;120,678-684. [PubMed]
 
Büller, HR, Agnelli, G, Hull, RD, et al Antithrombotic therapy for venous thromboembolic disease: the seventh ACCP conference on antithrombotic and thrombolytic therapy.Chest2004;126,401S-428S. [PubMed]
 
Prandoni, P, Lensing, AW, Piccioli, A, et al Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis.Blood2002;100,3484-3488. [PubMed]
 
Couban, S, Goodyear, M, Burnell, M, et al Randomized placebo-controlled study of low-dose warfarin for the prevention of central venous catheter-associated thrombosis in patients with cancer.J Clin Oncol2005;23,4063-4069. [PubMed]
 
Fagnani, D, Franchi, R, Porta, C, et al Thrombosis-related complications and mortality in cancer patients with central venous devices: an observational study on the effect of antithrombotic prophylaxis.Ann Oncol2007;18,551-555. [PubMed]
 
Chan, A, Iannucci, A, Dager, WE Systemic anticoagulant prophylaxis for central catheter-associated venous thrombosis in cancer patients.Ann Pharmacother2007;41,635-641. [PubMed]
 

Figures

Tables

Table Graphic Jump Location
Table 1. Clinical Characteristics and 3-Month Outcomes of the 11,564 DVT Patients According to the Location of DVT*
* 

Data are presented as No. (%) or mean ± SD unless otherwise indicated. NS = not significant.

Table Graphic Jump Location
Table 2. Three-Month Outcomes in 512 Patients With Arm DVT According to the Existence of Cancer and/or Catheter*
* 

Data are presented as No. (%) or mean ± SD unless otherwise indicated.

Table Graphic Jump Location
Table 3. Univariate Analysis on the Risk for Recurrent VTE or Major Bleeding in the 512 Patients With Arm DVT*
* 

Data are presented as No. (%) unless otherwise indicated. See Table 1 for expansion of abbreviation.

 

Two patients had major bleeding and recurrent VTE.

References

Tilney, NL, Griffiths, HJG, Edwards, EA (1970) Natural history of major venous thrombosis of the upper extremity.Arch Surg101,792-796. [PubMed] [CrossRef]
 
Prescott, SM, Tikoff, G Deep venous thrombosis of the upper extremity: a reappraisal.Circulation1979;59,350-355. [PubMed]
 
Demeter, SL, Pritchard, JS, Piedad, OH, et al Upper extremity thrombosis: etiology and prognosis.Angiology1982;33,743-755. [PubMed]
 
Davis, G, Kaplan, K, Kwaan, HC Pulmonary emboli from a platelet-rich thrombus attached to a pacemaker electrode.Pace1983;6,883-886. [PubMed]
 
Anderson, AJ, Krasnow, SH, Boyer, MW, et al Thrombosis: the major Hickman catheter complication in patients with solid tumor.Chest1989;95,71-75. [PubMed]
 
Becker, DM, Philbrick, JT, Walker, FB Axillary and subclavian venous thrombosis: prognosis and treatment.Arch Intern Med1991;151,1934-1943. [PubMed]
 
Lee, AYY, Levine, MN, Butler, G, et al Incidence, risk factors, and outcomes of catheter-related thrombosis in adult patients with cancer.J Clin Oncol2006;24,1404-1408. [PubMed]
 
Joffe, HV, Kucher, N, Tapson, VF, et al Upper-extremity deep vein thrombosis: a prospective registry of 592 patients.Circulation2004;110,1605-1611. [PubMed]
 
Prandoni, P, Bernardi, E, Marchiori, A, et al The long term clinical course of acute deep vein thrombosis of the arm: prospective cohort study.BMJ2004;329,484-485. [PubMed]
 
Martinelli, I, Battaglioni, T, Bucciarelli, P, et al Risk factors and recurrence rate of primary deep vein thrombosis of the upper extremities.Circulation2004;110,566-570. [PubMed]
 
Monreal, M, Falgá, C, Valdés, M, et al Fatal pulmonary embolism and fatal bleeding in cancer patients with venous thromboembolism: findings from the RIETE registry.J Thromb Haemost2006;4,1950-1956. [PubMed]
 
Trujillo-Santos, J, Herrera, S, Page, MA, et al Predicting adverse outcome in outpatients with acute deep vein thrombosis: findings from the RIETE Registry.J Vasc Surg2006;44,789-793. [PubMed]
 
López-Jiménez, L, Montero, M, González-Fajardo, JA, et al Venous thromboembolism in very elderly patients: findings from a prospective registry (RIETE).Haematologica2006;96,1046-1051
 
Nieto, JA, Bruscas, MJ, Ruiz-Ribo, D, et al Acute venous thromboembolism in patients with recent major bleeding: the influence of the site of bleeding and the time elapsed on outcome.J Thromb Haemost2006;4,2367-2372. [PubMed]
 
Monreal, M, Falgá, C, Valle, R, et al Venous thromboembolism in patients with renal insufficiency: findings from the RIETE Registry.Am J Med2006;119,1073-1079. [PubMed]
 
Spencer, FA, Emery, C, Lessard, D, et al Upper extremity deep vein thrombosis: a community-based perspective.Am J Med2007;120,678-684. [PubMed]
 
Büller, HR, Agnelli, G, Hull, RD, et al Antithrombotic therapy for venous thromboembolic disease: the seventh ACCP conference on antithrombotic and thrombolytic therapy.Chest2004;126,401S-428S. [PubMed]
 
Prandoni, P, Lensing, AW, Piccioli, A, et al Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis.Blood2002;100,3484-3488. [PubMed]
 
Couban, S, Goodyear, M, Burnell, M, et al Randomized placebo-controlled study of low-dose warfarin for the prevention of central venous catheter-associated thrombosis in patients with cancer.J Clin Oncol2005;23,4063-4069. [PubMed]
 
Fagnani, D, Franchi, R, Porta, C, et al Thrombosis-related complications and mortality in cancer patients with central venous devices: an observational study on the effect of antithrombotic prophylaxis.Ann Oncol2007;18,551-555. [PubMed]
 
Chan, A, Iannucci, A, Dager, WE Systemic anticoagulant prophylaxis for central catheter-associated venous thrombosis in cancer patients.Ann Pharmacother2007;41,635-641. [PubMed]
 
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