Venous Thromboembolism

Background

Venous thromboembolism (VTE) is a known complication of patients with cancer. Approximately 15% of patients with cancer will develop a VTE, and for some patients without cancer, a diagnosis of thrombosis may predict the development of a malignancy. Patients with VTE may also have reduced survival.¹ Tumor type, individual chemotherapy agents, and placement of vascular access devices can contribute to the development of a deep vein thrombosis (DVT) . Some specific tumor types associated with DVT are brain tumors and gastrointestinal cancers, including CRC.²

Patients with a new VTE may describe swelling, tenderness, or warmth in the affected extremity. These complaints should prompt a physical exam and, if warranted, a Doppler or radiologic exam to confirm the presence of VTE. Shortness of breath, chest pain, or cough may indicate a pulmonary embolism (PE), and in most cases, radiologic exam for this complication would include a radiologic scan, such as multislice computed tomographic pulmonary angiography to rule out PE.

Virchow’s triad (Figure 1) describes the components that play a role in the development of a thrombosis

Stasis
Vascular endothelial damage
Hypercoagulability

Most CRCs are adenocarcinomas and, as such, contain mucin,³ which could contribute to hypercoagulability. Many patients with CRC also receive chemotherapy, and some of these agents contribute to hypercoagulability (fluorouracil [5-FU], growth factors, and bevacizumab). Additionally, many patients receive central catheters, which can increase the risk of thrombosis by contributing to vascular endothelial damage. Lastly, many patients with CRC can suffer from fatigue, which can contribute to stasis.

Review of Literature

A retrospective analysis of all patients with CRC diagnosed in California during 1993-1995 and 1997-1999 showed that

Of 68,142 patients diagnosed with the disease, the 2-year cumulative incidence of thrombosis was 3.1% (or 2,100 patients)⁴
Approximately 5% of the patients developed VTE in the first 6 months after diagnosis, with a significantly decreased incidence rate after the first 6 months
Metastatic disease and a higher number of chronic medical comorbidities were the most important predictors of VTE
Almost one-third of the patients with incident VTE had reduced survival, leading the researchers to suspect that the presence of VTE might indicate a more biologically aggressive cancer

One hundred ninety-three patients with newly diagnosed CRC who were admitted for potentially curative surgery were examined with compression ultrasonography to detect the presence of DVT prior to surgery.¹ Of these patients

7.8% (15) had an existing DVT
16% in the female patients versus 2.6% in the male patients
1% of the patients had a pulmonary embolism (2 of 193)

The authors concluded that patients with CRC, especially women and those at higher risk, had a high preoperative prevalence of DVT.¹

Scappaticci and colleagues⁵ reported on the incidence of arterial or thromboembolic events during chemotherapy vs. chemotherapy plus bevacizumab in a variety of cancer types and chemotherapy regimens. They concluded that the combination treatment with bevacizumab and chemotherapy, compared with chemotherapy alone, was associated with an increased risk of arterial thromboembolism but not venous thromboembolism.

Risk factors for an arterial thromboembolic event included a prior arterial thromboembolic event or age >65 years. A summary of the study can be found here.

Patients with CRC who received central venous catheters to facilitate the delivery of 5-FU chemotherapy were also found to have a higher risk of VTE.⁶ These patients (7 of 350 or 2%) developed VTE after placement of a central venous catheter. This prompted investigators to suggest thromboprophylaxis in patients with D-dimers above 7.0 mcg/mL.

Because of the increased risk associated with surgery in CRC patients, clinicians should provide anticoagulant therapy, although the optimal thromboprophylaxic dose is not yet known. Simonneau and colleagues⁷ investigated the benefits of nadroparin (2,850 IU) and enoxaparin (4,000 IU) SC for 9 + 2 days in a randomized, double-blind study in 950 evaluable CRC patients undergoing CRC surgery. The results showed that the VTE rate was 15.9% in the patients treated with nadroparin and 12.6% in the enoxaparin group, with a rate of proximal DVT comparable between the two groups but a lower rate of symptomatic VTE in the patients receiving nadroparin. Less bleeding occurred with nadroparin, as well (7.3% vs 11.5%).

The benefits of sequential compression devices (SCD) also contribute to prophylaxis treatment for high-risk colorectal surgery patients. Ramirez and colleagues⁸ searched a computerized database for information on patients with CRC or inflammatory bowel disease over a 7-year period. Patients who had major abdominal surgery and received SCD for VTE prophylaxis were identified. Of these patients, 1,281 were classified as highest risk using published parameters by the American Society of Colon and Rectal Surgeons, with an incidence of clinically detectable postoperative VTE of 0.78%. Prophylaxis for perioperative VTE with SCD was found to be a treatment option for patients at highest risk in this study. A Cochrane review conducted in 2003 confirmed that graduated compression stockings in combination with low-dose unfractionated heparin or low molecular weight heparin provide the optimal prophylaxis for this population of patients in the prevention of VTE.⁹

Treatment of VTE in patients with CRC is virtually the same as for most patients with cancer and may include the use of heparins (either unfractionated or low molecular weight) and/or oral anticoagulants such as warfarin. There have been cautionary reports in the literature regarding the use of minidose warfarin in patients receiving chemotherapy treatment with FOLFOX (5-FU, leucovorin [LV], and oxaliplatin) or 5-FU/LV because an elevation in the international normalized ratio (INR) may occur.^{10, 11} Clinicians are urged to be aware of this potential drug interaction.

Patients with CRC have a higher risk for the development of VTE and benefit from anticoagulant prophylaxis with surgery. Additionally, chemotherapeutic treatments and placement of vascular access devices can increase their risk after surgery. Oncology nurses and clinicians caring for these patients should be aware of the risk for VTE and the signs and symptoms that may indicate the presence of a new thrombosis. Prompt recognition of VTE with appropriate anticoagulant therapy can help to improve patient outcome.

Clinical Practice Guidelines

The National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology version 1.2007 is available at: http://www.nccn.org/professionals/physician_gls/PDF/vte.pdf. Accessed: December 12, 2007.

The American Society of Clinical Oncology (ASCO) Guideline: Recommendations for Venous Thromboembolism Prophylaxis and Treatment in Patients with Cancer is available at: http://jco.ascopubs.org/cgi/reprint/JCO.2007.14.1283v1.pdf. Accessed: December 12, 2007.

An algorithm, based on the ASCO Guideline, is available as a patient tool is located here. Assessed December 12, 2007.

References

Stender MT, Nielsen TS, Frokjaer JB, et al. High preoperative prevalence of deep venous thrombosis in patients with colorectal cancer. Br J Surg. 2007 Apr 17; [Epub ahead of print]. Accessed September 3, 2007, from http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17440957&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Viale PH, Schwartz RN. Venous thromboembolism in patients with cancer Part I Survey of oncology nurses’ attitudes and treatment practices for ambulatory settings. Clin J Oncol Nurs. 2004;8:455-461.
Caine GJ, Stonelake PS, Lip GYH, Kehoe ST. The hypercoagulable state of malignancy: pathogenesis and current debate. Neoplasia, 2002;4:465-473.
Alcalay A, Wun T, Khatri V, et al. Venous thromboembolism in patients with colorectal cancer: incidence and effect on survival. J Clin Oncol. 2004;24:1112-1118.
Scappaticci FA, Skillings JR, Holden SN et al. Arterial Thromboembolic Events in Patients with Metastatic Carcinoma Treated with Chemotherapy and Bevacizumab. J Natl Can Inst. 2007;99:1232-1239. Available full text without charge or subscription at http://jnci.oxfordjournals.org/cgi/reprint/99/16/1232. Accessed September 3, 2007.
Yoshikawa R, Yanagi H, Noda M, et al. Venous thromboembolism in colorectal cancer patients with central venous catheters for 5-FU infusion-based pharmacokinetic modulating chemotherapy. Oncol Rep. 2005;13:627-632
Simonneau G, Laporte S, Mismetti P, et al. A randomized study comparing the efficacy and safety of nadroparin 2850 IU (0.3 mL) vs. enoxaprin 4000 IU (40 mg) in the prevention of venous thromboembolism after colorectal surgery for cancer. J Thromb Haemost. 2006;4:1693-1700.
Ramirez JI, Vassiliu P, Gonzalez-Ruiz C, et al. Sequential compression devices as prophylaxis for venous thrombosis in high-risk colorectal surgery patients: reconsidering American Society of Colorectal Surgeons parameters. Am Surg. 2003;69:941-945.
Wille-Jorgensen P, Rasmussen MS, Andersen BR, Borly L. Heparins and mechanical methods for thromboprophylaxis in colorectal surgery. Cochrane Database Syst Rev. 2003;(4):CD001217.
Magagnoli M, Masci G, Carnaghi C, et al. Minidose warfarin is associated with a high incidence of International Normalized Ratio elevation during chemotherapy with FOLFOX regimen. Ann Oncol. 2003;14:959-960.
Brown MC. An adverse interaction between warfarin and 5-fluorouracil: a case report and review of the literature. Chemotherapy. 1999;45:392-395

Key Definitions

adenocarcinomas—adeno means gland; carcinoma is a malignancy that begins in epithelial tissue accounting for 90%-95% of all CRC

compression ultrasonography—uses sound waves to visualize inside the leg. The patient lies supine, then prone as an ultrasound wand is applied to the leg. Considered the test of choice for suspected DVT

computed tomographic pulmonary angiography (CPTA)—effective method for diagnosing large pulmonary emboli; questionable for detecting small emboli

D-dimer—used to rule out DVT and often increased in individuals with VTE or PE. D-dimer molecules are released as the clot breaks down. A critical value is > 0.51 mg/L.

heparin (low molecular weight) (LMW)—about 3,000 daltons; generally given once daily SC, not IM. Dosages in units and mg are not interchangeable. Two examples: enoxaparin and nadroparin.

heparin (unfractionated)—naturally occurring; molecular weight of ~20,000-30,000 daltons; requires continuous dosing

mucin—an albumin-like substance found in mucous glands

sequential compression device (SCD)—alternating air current in a sleeve wrapped around the leg or arm to improve venous return and prevent stasis

thrombosis (deep vein) (DVT)—most commonly, a blood clot that forms in the deep veins of the leg; clots can form in the arms

thrombosis (prophylaxis)—usually heparins, to prevent clot formation in at-risk patients

thromboembolism (venous) (VTE)— a blood clot that forms in a vein

vascular endothelial damage—the flat cells that compose the inner lining of the entire circulatory system. They function to reduce friction, allowing blood to pass quickly and without trauma.

Virchow’s triad—in 1856 Rudolf Virchow is credited with identifying factors that led to the development of thrombosis. The triad is thought to have come later as research confirmed and refined his findings.

You've reached the end of this section.

[ Previous Page ] [ Home ]

This page was last modified on 12/14/2007, at 11:34:12 am ET.

You need to upgrade your Flash Player. Please upgrade here.

Keeping Current | Nurse-to-Nurse Forum | Resources | Side Effect and Symptom Management | Breaking News | Events