Originally published as JCO Early Release 10.1200/JCO.2005.06.084 on March 14 2005

This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Verso, M. Articles by Mosca, S. Search for Related Content PubMed PubMed Citation Articles by Verso, M. Articles by Mosca, S. Related Articles Related Editorial Social Bookmarking                            What's this?

Enoxaparin for the Prevention of Venous Thromboembolism Associated With Central Vein Catheter: A Double-Blind, Placebo-Controlled, Randomized Study in Cancer Patients

From the Sezione di Medicina Interna e Cardiovascolare, Dipartimento di Medicina Interna; Sezione di Anestesia, Analgesia e Terapia Intensiva, Dipartimento di Medicina Clinica e Sperimentale; and Istituto di Radiologia Diagnostica ed Interventistica, Università di Perugia, Perugia; Unità Operativa di Chirurgia Gastroenterologica, Dipartimento di Oncologia, and Dipartimento di Chirurgia, Istituto Nazionale per la Ricerca sul Cancro, Genua; Dipartimento di Medicina Clinica, Universita' dell'Insubria, Varese; Ospedale Evangelico Valdese, Turin; Divisione di Medicina, Ospedale di Gubbio, Gubbio; Unità di Patologia Vascolare e della Coagulazione, Azienda Ospedaliera di Parma, Parma; Unità Organica di Oncologia Medica e Sperimentale, Bari; Istituto Clinico Humanitas Rozzano, Milan; III° Unità Operativa di Medicina Interna e Oncoematologia, Ospedale di Piacenza, Piacenza; and Unità Operativa di Oncologia, Ospedale di Camposampiero, Padua, Italy

Address reprint requests to Melina Verso, MD, Sezione di Medicina Interna e Cardiovascolare, Dipartimento di Medicina Interna, Università di Perugia, Via Enrico dal Pozzo, 06123 Perugia, Italy; e-mail: agnellig{at}unipg.it

	ABSTRACT

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Appendix Authors' Disclosures of... REFERENCES

 
PURPOSE: The extent of venous thromboembolism (VTE) associated with central vein catheters (CVC) in cancer patients remains unclear. The aim of this study was to evaluate the efficacy and safety of the low molecular weight heparin, enoxaparin, in the prevention of VTE.

PATIENTS AND METHODS: In a multicenter, double-blind study, consecutive cancer patients scheduled for CVC insertion were randomly assigned to receive either subcutaneous enoxaparin 40 mg once a day or placebo. Treatment was started 2 hours before CVC insertion and continued for 6 weeks. The primary end points of the study were deep vein thrombosis (DVT), confirmed by venography of the CVC limb performed 6 weeks after randomization, or clinically overt pulmonary embolism, confirmed by objective testing during the study drug administration. Patients were assessed for bleeding complications.

RESULTS: Three hundred eighty-five patients were randomized, of which 321 (83.4%) underwent venography. A venography was adequate for adjudication in 155 patients in each treatment group. A DVT was observed in 22 patients (14.1%) treated with enoxaparin and in 28 patients (18.0%) treated with placebo, corresponding to a relative risk of 0.78 (95% CI, 0.47 to 1.31). No major bleeding occurred. Five patients (2.6%) in the enoxaparin group and two patients (1.0%) in the placebo group died during the treatment period.

CONCLUSION: In this study, no difference in the rate of CVC-related VTE was detected between patients receiving enoxaparin and patients receiving placebo. The dose of enoxaparin used in this study proved to be safe. Clinical trials evaluating higher enoxaparin doses could optimize the efficacy of this agent for this indication.

	INTRODUCTION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Appendix Authors' Disclosures of... REFERENCES

 
Venous thromboembolism (VTE) is a common complication in patients with cancer. In these patients VTE may occur at any stage of their disease; however, the risk is particularly high after surgery, during chemotherapy, and in association with central vein catheters (CVC).

In cancer patients, the use of long-term CVC facilitates chemotherapy, transfusions, parenteral nutrition, and blood sampling. Unfortunately, long-term CVC use is associated with an increased risk of infections and deep venous thrombosis (DVT). The incidence of clinically overt CVC-related VTE has been reported to vary between 0.3% and 28.3%,¹ and the incidence of CVC-related DVT, as assessed by venography, has been reported to range between 27% and 66%.¹ Pulmonary embolism (PE) has been reported to occur in 15% to 25% of cancer patients with CVC-related DVT.¹

Several studies^2-9 have evaluated the clinical benefit of antithrombotic prophylaxis for CVC-related VTE in cancer patients. Most of the initial studies were open-label studies and of limited sample size. There are no double-blind studies that evaluate the efficacy of prophylaxis of DVT by means of venography. Double-blind studies are also required to properly assess the incidence of bleeding complications associated with VTE prophylaxis in cancer patients. A safety assessment is particularly important because bleeding associated with the administration of anticoagulants is a major concern in cancer patients. We performed a multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of the low molecular weight heparin (LMWH), enoxaparin, administered for 6 weeks, for the prevention of VTE in cancer patients with CVC. In this study, venography, which was scheduled at the end of the study treatment, was used to assess the incidence of upper limb DVT.

	PATIENTS AND METHODS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Appendix Authors' Disclosures of... REFERENCES

 
Study Patients
Consecutive cancer patients aged 18 years or older who were scheduled for CVC insertion for chemotherapy were eligible for the study if they had a life expectancy of at least 3 months and adequate venous access to perform venography of the upper limb and if the CVC was to be left in site for longer than 6 weeks. The exclusion criteria were renal failure (serum creatinine > 2.0 mg/dL [180 µmol/L]); known hypersensitivity to x-ray contrast medium; previous CVC insertion on the ipsilateral side; cerebral thrombosis or bleeding in the previous 6 months or known cerebral metastasis; bleeding disorders (activated partial thromboplastin time and/or prothrombin time 30% longer than the control values) or platelet count less than 80 x 10⁹/L; active gastric peptic ulcer or severe hepatic disease; uncontrolled arterial hypertension (diastolic pressure > 120 mmHg, despite treatment); known hypersensitivity to unfractionated heparin or LMWHs; objectively confirmed DVT within the previous 3 months; treatment with heparin, LMWH, oral anticoagulants, or antiplatelet agents within 5 days before CVC insertion; pregnancy; anticipated inability to participate in the study for 3 months; and consent refusal. Patients having CVC inserted for total parenteral nutrition only were excluded from the study. The study protocol was approved by the ethical committees of the participating centers. Patients provided written informed consent.

Second-generation polyurethane or silicon catheters of 6 to 9.5 F (including the totally implantable CVCs) were allowed in the study. The correct position of the catheter tip (at the junction of the superior caval vein and the right atrium) was checked by chest x-ray or fluoroscopic examination on the same day of CVC insertion.

Study Design and Interventions
This study was designed as a multicenter, randomized, double-blind, placebo-controlled study. The study was performed in 11 Italian centers.

On the day of CVC insertion, eligible patients were randomly assigned to receive subcutaneously either enoxaparin (Clexane; Aventis Pharmaceutical, Milan, Italy) at the dose of 40 mg once daily or placebo by using preloaded syringes. The first dose of study medication was administered 2 hours before CVC insertion, and the treatment was continued for 42 ± 2 days. Permuted blocks of four were used for treatment allocation. Concomitant treatment with aspirin, other antiplatelet agents, or nonsteroidal anti-inflammatory agents was not allowed during the trial.

Competent patients or their caregivers or nurses were trained about the injection procedure. The amount of dispensed ampoules of study drug was recorded. Compliance was checked by counting the returned empty or full syringes.

The interruption of study drug administration was recommended when thrombocytopenia occurred. The study drug was to be withdrawn when the platelet count decreased to less than 70,000/µL and resumed when the platelet count returned above this value.

Assessment of End Points
The primary efficacy end point of the study was the composite of upper limb DVT, confirmed by venography (CVC limb) performed 6 weeks after random assignment, or clinically overt PE, confirmed by objective testing during study drug administration. Upper CVC limb venography was scheduled at the end of the treatment period (day 42 ± 2) or earlier if there was a clinical suspicion of upper limb DVT or PE or compulsory catheter removal. Venography was performed using a nonionic contrast agent¹⁰ infused in an antecubital vein of the ipsilateral arm. Venographies were evaluated by a central adjudication committee consisting of three radiologists who were unaware of the patients’ clinical status, the assigned treatment, or the local interpretation of the venography result. The adjudicating panel first classified venography as adequate or inadequate. A venography was considered adequate if the entire deep venous system was visualized from the axillary vein to the superior vena cava. An upper limb DVT was defined as an intraluminal filling defect in a deep vein of the upper limb if it was constantly seen on two or more views or after a second injection of contrast medium. Symptomatic PE was to be confirmed by high-probability ventilation-perfusion lung scanning, thoracic computed tomography scan, pulmonary angiography, or autopsy. Secondary efficacy end points were clinically overt thromboembolic events confirmed by objective testing, death from thromboembolic disease, or death from any cause during the study treatment period or within 3 months from its completion.

The main safety end point was major bleeding. Bleeding was considered major when it was clinically overt and associated with a decrease in the hemoglobin level of at least 2 g/dL or requiring a transfusion of two or more units of packed red cells. Intracranial, retroperitoneal, and intraocular bleeding and bleeding requiring surgical intervention and withdrawal of treatment were also considered major. All other bleedings were considered minor.

Data on clinically overt events and bleedings were reviewed by a central panel unaware of treatment assignment. The central panel also classified all deaths as caused by PE, bleeding, cancer progression, or other causes. To analyze the cause of death and the data on bleeding, the central panel received all relevant information available.

Surveillance Program and Follow-Up
Patients were assessed at the scheduled visits (at 7 ± 2 days, at 14 ± 2 days, and 42 ± 2 days after CVC insertion) to ensure their compliance with the study protocol and to review their clinical status; special attention was paid to symptoms and signs of VTE, bleeding, and other adverse events. Each scheduled visit also included blood sampling for CBC count and measurement of liver enzymes and renal function. In case of symptoms and/or signs suggestive of VTE, patients were instructed to contact the investigators and, if the clinical suspicion of upper limb DVT was confirmed, venography of the CVC upper limb was performed within 24 hours. If venography was positive, the patient was treated with unfractionated heparin, LMWH, or warfarin, as appropriate. If venography was negative, the patients continued to receive the study drug until the scheduled venography at the end of the treatment period, according to the study protocol. Pharmacologic prophylaxis of upper limb DVT after the scheduled venography was left to the discretion of the attending physician. Patients with clinical features suggestive of PE were scheduled to undergo perfusion lung scanning. A normal perfusion scan ruled out PE. A high-probability scan, defined as a scan showing one or more segmental or larger perfusion defects with relatively preserved ventilation, or an intermediate-probability lung scan associated with documented DVT was considered to confirm the diagnosis. Patients with nondiagnostic lung scans were scheduled to undergo pulmonary angiography or thoracic computed tomography scan.

Patients were subsequently monitored by means of hospital visits or telephone contacts to record the occurrence of clinically overt VTE, bleeding, or death. Follow-up started immediately after venography or at study withdrawal when this occurred. For all patients, the overall duration of follow-up was 3 months.

Statistical Analysis
The primary efficacy analysis compared the rate of the composite of upper limb DVT as screened by mandatory venography or confirmed symptomatic PE in patients receiving enoxaparin and in patients receiving placebo. Data analysis was performed on an intent-to-treat basis. The intent-to-treat population was defined as all randomized patients who received at least one dose of study medication and underwent venography of the CVC limb or had a confirmed symptomatic PE.

The safety analysis compared the rates of bleeding between the enoxaparin and placebo groups. All patients receiving at least one dose of the study treatment were included in the safety analysis.

The evaluation of the sample size was based on the estimated rates of venography-detected upper limb DVT at day 42 ± 2 in the two treatment groups. On the basis of previous venography studies,^2,3 an incidence of VTE of 30% in the control group and of 15% in the enoxaparin group was assumed. To demonstrate this 50% risk reduction with an of 5% and a ß of 80% in a two-sided test, approximately 150 patients for each group were required. Assuming a drop out rate of 25% of enrolled patients, a total of 400 patients was to be included in the study.

The rates of VTE events and bleedings were compared using the ² test.¹¹ Relative risks and 95% CIs were calculated. The reported P values are based on two-sided tests.

	RESULTS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Appendix Authors' Disclosures of... REFERENCES

 
Between March 2000 and March 2003, 385 patients were entered onto the study; 191 patients were assigned to enoxaparin, and 194 were assigned to placebo (Fig 1). Because the drop out rate was lower than expected (17% instead of 25%), the recruitment was stopped after the inclusion of 385 patients when it was clear that we would have more than 300 assessable patients.

View larger version (16K): [in this window] [in a new window]   Fig 1. Study population. VTE, venous thromboembolism.

VTE
The overall incidence of venography-detected upper limb DVT was 16.1% (50 of 310 patients). In the enoxaparin group, the incidence of DVT was 14.1% (22 of the 155 patients), and in the placebo group, the incidence of DVT was 18.0% (28 of the 155 patients), corresponding to a relative risk of 0.78 (95% CI, 0.47 to 1.31; P = .35).

DVT was occlusive in 14 patients and nonocclusive in 36 patients. Eight cases (2.1%) of symptomatic upper limb DVT were observed; two cases (1.0%) were in the enoxaparin group, and six cases (3.1%) were in the placebo group, corresponding to a relative risk of 0.32 (95% CI, 0.07 to 1.66). Only one patient with an upper limb DVT presented clinical signs or symptoms of PE during the study period. None of the patients who were randomized but not included in the analyzed population had a symptomatic VTE event.

Bleeding Episodes
One hundred eighty-nine patients in the enoxaparin group (98.9%) and 193 patients in the placebo group (99.5%) completed the study treatment. No major bleeding was observed in either group. During the treatment period, 12 episodes of minor bleeding were observed in the enoxaparin group (6.3%), and seven episodes were observed in the placebo group (3.6%), corresponding to a relative risk of 1.75 (95% CI, 0.70 to 4.33). No bleeding complications associated with the procedure of the CVC insertion were observed.

Deaths
During the study drug administration, five patients in the enoxaparin group and two patients in the placebo group died. These patients all died of cancer progression. The five patients in the enoxaparin group who died had gastrointestinal, head and neck, breast, genital, and metastatic cancer of unknown origin (one patient each). The two patients in the placebo group who died had gastrointestinal cancer and lymphoma (one patient each).

Thrombocytopenia
Nine patients (4.7%) in the enoxaparin group and 12 patients (6.2%) in the placebo group developed thrombocytopenia during the administration of the study treatment. This was definitively discontinued in eight patients (four patients in each treatment group), whereas in five enoxaparin patients and in eight placebo patients, the study treatment was restarted after a median of 10.5 and 11 days, respectively.

Follow-Up
During the follow-up period, three patients (1.6%) in the placebo group and none in the enoxaparin group presented a clinically overt VTE event. Eight patients in the enoxaparin group and 18 in the placebo group died during the follow-up period (relative risk, 0.46; 95% CI, 0.20 to 1.02). Most of the patients died from cancer progression. The eight patients in the enoxaparin group who died had breast cancer (three patients), gastrointestinal cancer (two patients), lymphoma (two patients), and cancer of unknown origin (one patient). The 18 patients in the placebo group had gastrointestinal cancer (10 patients), lymphoma (seven patients), and breast cancer (one patient). Overall, 13 enoxaparin patients and 20 placebo patients died during the study period.

	DISCUSSION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Appendix Authors' Disclosures of... REFERENCES

 
This is the first randomized, double-blind study that evaluated the efficacy and safety of prophylaxis of CVC-related venous thrombosis in patients with cancer by means of venography. The observed incidence of CVC-related DVT without prophylaxis was 18%, and the administration of 40 mg of enoxaparin resulted in a non–statistically significant 21.4% reduction in the rate of the thrombosis. The incidence of bleeding was low and similar in the two groups.

The 18% rate of CVC-related DVT in patients receiving placebo was lower than anticipated in the study hypothesis because it was lower than the rates observed in two previous controlled venography studies (37.5% and 62%).^2,3 It is uncertain but quite likely that this low rate is a result of the improved biocompatibility of the CVCs currently used and/or to the less-invasive insertion procedures. We observed an incidence of clinically overt events of 2%. The ratio between venography-detected DVT and clinically overt VTE event is consistent with other studies on the prophylaxis of DVT of the lower limbs in surgical and medical conditions.¹²

The relative risk reduction associated with enoxaparin was also lower than that anticipated in the study hypothesis and lower than that seen in previous venography studies performed in the late 1980s and early 1990s with the LMWH dalteparin and warfarin.^2,3 However, our results are not completely unexpected when we consider the results of more recent studies that challenged the efficacy of LMWH and warfarin in the prevention of clinically overt CVC-related DVT in patients with cancer.^5-9 The overall low incidence of thromboembolic events and the lower than anticipated risk reduction obtained with enoxaparin reduced the power of our study to detect a clinically important difference.

The treatment period in our study was limited to 6 weeks. This choice was based on previous observations that indicated that the majority of VTE events occur during the first 6 weeks after CVC insertion.^13,14 However, we cannot exclude that extending the treatment period beyond 6 weeks could have given a higher overall rate of thrombosis in the placebo group and a greater treatment efficacy.

The administration of enoxaparin was not associated with any excessive bleeding compared with placebo. This observation leaves open the option for increasing the dose of enoxaparin in this condition. Increasing the dose is biologically plausible given the hypercoagulability observed in cancer patients. Further studies are required to assess whether a dose of enoxaparin higher than the dose used in this study could be more effective and just as safe. We did not observe any bleeding complication associated with the procedure of the CVC insertion. This observation may be important because prophylaxis with enoxaparin was started before the CVC insertion.

In conclusion, our study showed that the incidence of venography-screened upper limb DVT associated with CVC in cancer patients is lower than previously reported. Our findings do not prove the efficacy of enoxaparin for the prophylaxis of CVC-related thrombosis in cancer patients. An increased dose of enoxaparin could improve the results obtained in our study. Pending the results of further studies, the recommendation of using routine prophylaxis in these patients should be reconsidered.

	Appendix

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Appendix Authors' Disclosures of... REFERENCES

 
The following investigators participated in this study: Istituto Nazionale per la Ricerca sul Cancro, Genua: A. Grasso, P. Meszaros, L. Moresco; Università di Perugia, Perugia: M. Tonato, M. Betti, A. Del Favero, M. Martelli; Universita’ dell’Insubria, Varese: A. Squizzato; Ospedale Evangelico Valdese, Turin: A. Vaccarino; Ospedale di Gubbio, Gubbio: O. Cazzato; Azienda Ospedaliera di Parma, Parma: S. Salvagni, D. Gasparro; Istituto Clinico Humanitas Rozzano, Milan: L. Castagna, B. Sarina; Ospedale di Piacenza: A. Lazzaro, D. Vallisa, L. Cavanna; Ospedale di Camposampiero: F. Gaion; and Ospedale di Ancona: G. Leoni.

	Authors' Disclosures of Potential Conflicts of Interest

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Appendix Authors' Disclosures of... REFERENCES

 
The authors indicated no potential conflicts of interest.

	NOTES

 
Supported by a grant-in-aid from Aventis, Bridgewater, NJ. This study was an investigator-initiated study.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

	REFERENCES

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Appendix Authors' Disclosures of... REFERENCES

 
1. Verso M, Agnelli G: Venous thromboembolism associated with long-term use of central venous catheters in cancer patients. J Clin Oncol 21:3665-3675, 2003[Abstract/Free Full Text]

2. Bern HM, Lokich JJ, Wallach SR, et al: Very low dose of warfarin can prevent thrombosis in central venous catheters: A randomized, prospective trial. Ann Intern Med 112:423-428, 1990

3. Monreal M, Alastrue A, Rull M, et al: Upper extremity deep venous thrombosis in cancer patients with venous access devices: Prophylaxis with a low molecular weight heparin (Fragmin). Thromb Haemost 75:251-253, 1996[Medline]

4. Boraks P, Seale J, Price J, et al: Prevention of central venous catheter associated thrombosis using minidose warfarin in patients with haematological malignancies. Br J Haematol 101:483-486, 1998[CrossRef][Medline]

5. Massicotte P, Julian JA, Gent M, et al: An open-label randomized controlled trial of low molecular weight heparin for the prevention of central venous line related thrombotic complications in children: The PROTEKT trial. Thromb Res 109:101-108, 2003[CrossRef][Medline]

6. Reichardt P, Kretzschmar A, Biakhov M, et al: A phase III, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of daily low-molecular-weight-heparin (dalteparin sodium) in preventing catheter-related complications (CRCs) in cancer patients with central venous catheters (CVCs). ASCO Annual Meeting, 2002 (abstr 1474)

7. Lagro SW, Verdonck LF, Borel Rinkes IH, et al: No effect of nadroparin prophylaxis in the prevention of central venous catheter (CVC)-associated thrombosis in bone marrow transplant recipients. Bone Marrow Transplant 26:1103-1106, 2000[CrossRef][Medline]

8. Heaton DC, Han DY, Inder A: Minidose (1 mg) warfarin as prophylaxis for central vein catheter thrombosis. Intern Med J 32: 84-88; 2002[CrossRef][Medline]

9. Couban S, Goodyear M, Burnell M, et al: A randomized double blind placebo-controlled study of low dose warfarin for the prevention of symptomatic central venous catheter-associated thrombosis in patients with cancer. Blood 100:703a, 2002 (abstr 2769)

10. Maas R, Nicolas U, Mugge-Hamann U, et al: Phlebography of the upper extremity: I. The technique and findings in 230 studies. Rofo 162:33-38, 1995[Medline]

11. Fleiss JL: Statistical Methods for Rates and Proportions (ed 2). New York, NY, John Wiley, 1981, pp 19-27

12. Geerts H, Heit JA, Clagett GP, et al: Prevention of venous thromboembolism. Chest 119:132-175, 2001 (suppl 1)

13. De Cicco M, Matovic M, Balestrieri L, et al: Central venous thrombosis: An early and frequent complication in cancer patients bearing long term silastic catheter—A prospective study. Thromb Res 86:101-113, 1997[CrossRef][Medline]

14. Luciani A, Clement O, Halimi P, et al: Catheter-related upper extremity deep venous thrombosis in cancer patients: A prospective study based on Doppler US. Radiology 220:655-660, 2001[Abstract/Free Full Text]

Submitted June 14, 2004; accepted November 18, 2004.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Related Editorial

• Catheter-Associated Thrombosis: Thromboprophylaxis or Not?
  M. Levine and A.K. Kakkar
  JCO 2005 23: 4006-4008 [Full Text]

This article has been cited by other articles:

				A. A. Khorana, M. B. Streiff, D. Farge, M. Mandala, P. Debourdeau, F. Cajfinger, M. Marty, A. Falanga, and G. H. Lyman Venous Thromboembolism Prophylaxis and Treatment in Cancer: A Consensus Statement of Major Guidelines Panels and Call to Action J. Clin. Oncol., October 10, 2009; 27(29): 4919 - 4926. [Abstract] [Full Text] [PDF]

				A. A. Khorana and G. C. Connolly Assessing Risk of Venous Thromboembolism in the Patient With Cancer J. Clin. Oncol., October 10, 2009; 27(29): 4839 - 4847. [Abstract] [Full Text] [PDF]

				S. P. Shivakumar, D. R. Anderson, and S. Couban Catheter-Associated Thrombosis in Patients With Malignancy J. Clin. Oncol., October 10, 2009; 27(29): 4858 - 4864. [Abstract] [Full Text] [PDF]

				A. A. Khorana Cancer and thrombosis: implications of published guidelines for clinical practice Ann. Onc., October 1, 2009; 20(10): 1619 - 1630. [Abstract] [Full Text] [PDF]

				P. Debourdeau, D. Kassab Chahmi, G. Le Gal, I. Kriegel, E. Desruennes, M.-C. Douard, I. Elalamy, G. Meyer, P. Mismetti, M. Pavic, et al. 2008 SOR guidelines for the prevention and treatment of thrombosis associated with central venous catheters in patients with cancer: report from the working group Ann. Onc., September 1, 2009; 20(9): 1459 - 1471. [Abstract] [Full Text] [PDF]

				N. Starling, S. Rao, D. Cunningham, T. Iveson, M. Nicolson, F. Coxon, G. Middleton, F. Daniel, J. Oates, and A. R. Norman Thromboembolism in Patients With Advanced Gastroesophageal Cancer Treated With Anthracycline, Platinum, and Fluoropyrimidine Combination Chemotherapy: A Report From the UK National Cancer Research Institute Upper Gastrointestinal Clinical Studies Group J. Clin. Oncol., August 10, 2009; 27(23): 3786 - 3793. [Abstract] [Full Text] [PDF]

				M. De Cicco, M. Matovic, L. Balestreri, A. Steffan, R. Pacenzia, M. Malafronte, D. Fantin, C. A. Bertuzzi, F. Fabiani, S. Morassut, et al. Early and short-term acenocumarine or dalteparin for the prevention of central vein catheter-related thrombosis in cancer patients: a randomized controlled study based on serial venographies Ann. Onc., June 30, 2009; (2009) mdp235v1. [Abstract] [Full Text] [PDF]

				A. A. Khorana and G. H. Lyman Incidence and Prevention of Cancer-associated Thrombosis ASCO Educational Book, January 1, 2009; 2009(1): 321 - 325. [Abstract] [Full Text] [PDF]

				D. E. Gerber, J. B. Segal, M. Y. Levy, J. Kane, R. J. Jones, and M. B. Streiff The incidence of and risk factors for venous thromboembolism (VTE) and bleeding among 1514 patients undergoing hematopoietic stem cell transplantation: implications for VTE prevention Blood, August 1, 2008; 112(3): 504 - 510. [Abstract] [Full Text] [PDF]

				W. H. Geerts, D. Bergqvist, G. F. Pineo, J. A. Heit, C. M. Samama, M. R. Lassen, and C. W. Colwell Prevention of Venous Thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) Chest, June 1, 2008; 133(6_suppl): 381S - 453S. [Abstract] [Full Text] [PDF]

				A. A. Khorana, N. M. Kuderer, E. Culakova, G. H. Lyman, and C. W. Francis Development and validation of a predictive model for chemotherapy-associated thrombosis Blood, May 15, 2008; 111(10): 4902 - 4907. [Abstract] [Full Text] [PDF]

				S. Vescia, A. K. Baumgartner, V. R. Jacobs, M. Kiechle-Bahat, A. Rody, S. Loibl, and N. Harbeck Management of venous port systems in oncology: a review of current evidence Ann. Onc., January 1, 2008; 19(1): 9 - 15. [Abstract] [Full Text] [PDF]

				A. Falanga, A. Y. Y. Lee, M. B. Streiff, and G. H. Lyman Anticoagulation in the Treatment of Venous Thromboembolism in Patients with Cancer ASCO Educational Book, January 1, 2008; 2008(1): 258 - 268. [Abstract] [Full Text] [PDF]

				F. A. Spencer, D. Lessard, C. Emery, G. Reed, and R. J. Goldberg Venous Thromboembolism in the Outpatient Setting Arch Intern Med, July 23, 2007; 167(14): 1471 - 1475. [Abstract] [Full Text] [PDF]

				D Fagnani, R Franchi, C Porta, P Pugliese, K Borgonovo, A Bertolini, M Duro, A Ardizzoia, V Filipazzi, L Isa, et al. Thrombosis-related complications and mortality in cancer patients with central venous devices: an observational study on the effect of antithrombotic prophylaxis Ann. Onc., March 1, 2007; 18(3): 551 - 555. [Abstract] [Full Text] [PDF]

				H. C. Kwaan Double Hazard of Thrombophilia and Bleeding in Leukemia Hematology, January 1, 2007; 2007(1): 151 - 157. [Abstract] [Full Text] [PDF]

				D. Gaitini, N. Beck-Razi, N. Haim, and B. Brenner Prevalence of Upper Extremity Deep Venous Thrombosis Diagnosed by Color Doppler Duplex Sonography in Cancer Patients With Central Venous Catheters. J. Ultrasound Med., October 1, 2006; 25(10): 1297 - 1303. [Abstract] [Full Text] [PDF]

				A Fennerty Venous thromboembolic disease and cancer. Postgrad. Med. J., October 1, 2006; 82(972): 642 - 648. [Abstract] [Full Text] [PDF]

				A. Y.Y. Lee, M. N. Levine, G. Butler, C. Webb, L. Costantini, C. Gu, and J. A. Julian Incidence, Risk Factors, and Outcomes of Catheter-Related Thrombosis in Adult Patients With Cancer J. Clin. Oncol., March 20, 2006; 24(9): 1404 - 1408. [Abstract] [Full Text] [PDF]

				G. Ferretti, E. Bria, A. Felici, P. Carlini, D. Giannarelli, M. Ciccarese, P. Papaldo, A. Fabi, A. Gelibter, and F. Cognetti Catheter-associated thrombosis: thromboprophylaxis for cancer patients who carry factor V Leiden? Ann. Onc., March 1, 2006; 17(3): 528 - 529. [Full Text] [PDF]

				M. Karthaus, A. Kretzschmar, H. Kroning, M. Biakhov, D. Irwin, N. Marschner, C. Slabber, G. Fountzilas, A. Garin, N. G. F. Abecasis, et al. Dalteparin for prevention of catheter-related complications in cancer patients with central venous catheters: final results of a double-blind, placebo-controlled phase III trial Ann. Onc., February 1, 2006; 17(2): 289 - 296. [Abstract] [Full Text] [PDF]

				E. A. Krzywda and D. A. Andris Twenty-five Years of Advances in Vascular Access: Bridging Research to Clinical Practice Nutr Clin Pract, December 1, 2005; 20(6): 597 - 606. [Abstract] [Full Text] [PDF]

				G. Curigliano, M. Colleoni, M. Mandala, T. De Pas, G. Spitaleri, F. de Braud, and A. Goldhirsch Prophylaxis for Venous Thromboembolism in Cancer Patients With a Central Vein Catheter: New Tones for an Old Song J. Clin. Oncol., October 1, 2005; 23(28): 7243 - 7244. [Full Text] [PDF]

				M. Levine and A.K. Kakkar Catheter-Associated Thrombosis: Thromboprophylaxis or Not? J. Clin. Oncol., June 20, 2005; 23(18): 4006 - 4008. [Full Text] [PDF]

This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Verso, M. Articles by Mosca, S. Search for Related Content PubMed PubMed Citation Articles by Verso, M. Articles by Mosca, S. Related Articles Related Editorial Social Bookmarking                            What's this?