**5. Ambulatory cancer patients**

Cancer patients treated in the outpatient setting can also be at high risk for VTE. Current guidelines do not recommend anticoagulant prophylaxis for ambulatory cancer patients. Khorana et al tried to establish a risk assessment model for VTE prophylaxis in ambulatory cancer patients after the initiation of chemotherapy. Five predictive variables were identified in a multivariate model: site of cancer (2 points for very high-risk site, 1 point for high-risk site), platelet count of 350 x 109/L or more, hemoglobin less than 100 g/L (10 g/dL) and/or use of erythropoiesis-stimulating agents, leukocyte count more than 11 x 109/L, and body mass index of 35 kg/m2 or more (1 point each). Rates of VTE in the validation part of their study were 0.3% in low-risk (score = 0), 2.0% in intermediate-risk (score = 1-2), and 6.7% in high-risk (score 3) category over a median of 2.5 months. The application of this model can identify patients with a nearly 7% short-term risk of symptomatic VTE and may be used to select cancer outpatients for studies of thromboprophylaxis (Khorana et al., 2008).

More recently, researchers focused on biomarkers that can predict the occurrence of VTE. Pselectin, found in the α granules of platelets and endothelial cells and expressed on the cell surface on activation, mediates the adhesion of leukocytes, platelets, and cancer cells in inflammation, thrombosis, and cancer growth and metastasis ( Chen et al., 2006). Recent studies have demonstrated that high plasma levels of soluble P-selectin are strongly associated with VTE (Rectenwald et al., 2005). In a prospective cohort study, P-selectin was also shown to be a risk factor for recurrent VTE (Kyrle et al., 2007).

In a recent study, the Vienna Cancer and Thrombosis Study (VCATS) group reported that elevated serum P-selectin levels predicts VTE in 687 newly diagnosed cancer patients. The cumulative probability of VTE after 6 months of follow up was 11.9% in patients with serum P-selectin above and 3.7% in those below the 75th percentile (P = 0.002). Authors postulated that such biomarker could identify cancer patient who may benefit from prophylaxis (Ay et al., 2008).

Venous Thromboembolism Prophylaxis in Cancer Patients 117

confidence interval 7-44). Bleeding events were not increased with prolonged compared

A recent meta-analysis of eligible clinical studies compared safety and efficacy of extended use of LMWH (for three to four weeks after surgery) versus conventional in-hospital prophylaxis among patients undergoing major abdominal surgeries. The indication for surgery was neoplastic disease in 70.6% (780/1104) of patients. The administration of extended LMWH prophylaxis significantly reduced the incidence of VTE, 5.93% versus 13.6%, RR 0.44 (CI 95% 0.28 - 0.7); DVT 5.93% versus 12.9%, RR 0.46 (CI 95% 0.29 - 0.74); proximal DVT 1% versus 4.72%, RR 0.24 (CI 95% 0.09 - 0.67). These superior efficacy results were obtained with no significant difference in major or minor bleeding between the two groups: 3.85% in the extended thrombo-prophylaxis group versus 3.48% in the conventional prophylaxis group; RR 1.12 (CI 95% 0.61 - 2.06) (Bottaro et al., 2008). Given the results of these studies, one can conclude that extended thromboprophylaxis with LMWH should be considered as a safe and useful strategy to prevent VTE in high-risk major abdominal and pelvic surgeries especially in cancer patients. Similar conclusions were reached in a more recent Cochrane database analysis (Rasmussen et al., 2009). Results of these studies are

Central venous catheters (CVC) are commonly inserted in cancer patient and are utilized to deliver chemotherapy, blood and blood component transfusion and occasionally for blood sampling. Central catheter per se is a risk factor for VTE, this risk is even higher when such catheters are placed in cancer patients especially so when used for active chemotherapy

Fig. 1. Extended out-of-hospital VTE prophylaxis for cancer patients undergoing major

with short-term thromboprophylaxis (Rasmussen et al., 2006).

(Bona, 1999; Rooden et al., 2005; Rosovsky & Kuter, 2005).

summarized in Figure-1.

surgery

**7. Central venous catheters** 

The concept of VTE prophylaxis for ambulatory cancer patients was tested in a recent double-blind study; patients with metastatic or locally advanced cancer of lung, colo-rectal, stomach, ovary, pancreas, or bladder who are initiating a new chemotherapy course, were randomized to receive subcutaneous semuloparin ( a new ultra low molecular weight heparin) or placebo. The drug was given at a dose of 20 mg subcutaneously and continued until change of chemotherapy. Twenty of the 1,608 patients treated with semuloparin (1.2%) and 55 of the 1,604 patients treated with placebo (3.4%) had a thromboembolic event, representing a 64% risk reduction in such event rate (hazard ratio [HR] = 0.36, 95% confidence interval [CI] 0.21–0.60, p<0.0001, intent-to-treat analysis). Nineteen of 1,589 patients (1.2%) in the semuloparin and 18 of the 1,583 patients (1.1%) in the placebo group had a major bleeding (HR=1.05, 95%CI 0.55 to 1.99) (Agnelli et al., 2011).

More work is needed before taking findings of these studies to clinical practice; as such ambulatory cancer patients on active chemotherapy may be considered for VTE prophylaxis based on risk level and clinical judgment.
