**12.1 Cancer-related factors**

#### **12.1.1 Site of cancer**

In studies looking at pooled groups of patients with different types of malignancy, the rate of VTE is consistently highest in patients with cancer of the pancreas, stomach, brain, kidney, uterus, lung or ovary 128,129,130,131.

Both large retrospective studies by Stein et al and Chew et al based on discharge claims databases reported the highest rates of VTE in patients with pancreatic cancer (4.3% and 5.3%, respectively). Patients with stomach cancer had the second and third highest risk of developing VTE in these studies 128,132. In patients with testicular and lung cancer, those with metastases to the liver and brain were shown to have higher rates of VTE compared with patients with other sites of metastases 133,134. The rates of VTE for specific types of cancer have been reported in many studies.

#### **12.1.2 Cancer stage**

Multiple studies have shown an increased risk of VTE in patients with advanced-stage cancer. In a retrospective study of over 500 000 patients from the California Cancer Registry, patients with metastatic cancer stage were twice as likely to have developed VTE in the year

Risk Factors of Deep Vein Thrombosis 13

Surgery is a well-known risk factor for development of VTE in patients without cancer. The incidence of DVT in cancer patients undergoing general surgery is estimated at 37% compared with 20% in patients without cancer 150. Factors related to immobility, tissue destruction and venous stasis are likely to be related to the increased risk of VTE after

Indwelling central venous catheters (CVC) greatly facilitate treatment in cancer patients, but they are also associated with complications including a significant risk of catheter-associated thrombosis. The incidence of symptomatic catheter-related DVT in adult patients ranges from 0.3% to 28%, while the rate of catheter-related DVT assessed by venography is 27–

Studies have not consistently demonstrated an association between use of haematopoietic growth factors and risk of cancer-associated VTE. İn a prospective study of ambulatory patients receiving chemotherapy, both the use of white cell growth factors and the use of red cell growth factors or decreased haemoglobin were independent predictors of VTE in multivariate analysis 152. This association was only significant in types of cancer already known to have high rates of thrombosis, and it is possible that these agents are used more frequently in patients with other markers of poor prognosis or more aggressive disease.

The authors' group was the first to identify an elevated prechemotherapy platelet count as a significant risk factor for cancer-associated thrombosis 152. In a prospective study of outpatients receiving chemotherapy, 21.9% had a platelet count of 350 000/mm3 or more prior to starting chemotherapy. The incidence of VTE was 3.98% (1.66% per month) for these patients, which was significantly higher than the rate of 1.25% (0.52% per month) for patients with a prechemotherapy platelet count of less than 200 000/mm3 (P for trend¼ 0.0003). The distribution of rechemotherapy platelet counts in patients who subsequently developed VTE was significantly higher than that for patients who did not develop VTE (t-

Tissue factor (TF), a transmembrane glycoprotein present on subendothelial tissue, platelets and leukocytes, is a key component in the initiation of coagulation and may play a role in cancer- associated thrombosis 153-155. The authors recently demonstrated a correlation between the level of TF expression in pancreatic tumours and subsequent development of VTE 156. VTE was four-fold more common (P ¼ 0.04) among patients with high TFexpressing carcinomas (26.5%) than among patients with low TF-expressing carcinomas

From 1979 to 1999, among 40,787,000 patients hospitalized in short-stay hospitals with any of 19 malignancies studied, 827,000 (2.0%) had VTE.157 This was twice the incidence in patients without these malignancies.157 The highest incidence of VTE was in patients with

**12.5 Surgery** 

surgery.

66%151.

**12.6 Indwelling catheters** 

**12.7 Platelet and leukocyte counts** 

**12.8 Tissue factor** 

(5.5%).

test P ¼0.002, Wilcoxon rank sum test P ¼0.0002).

prior to diagnosis of cancer 135. In a population-based case–control study of patients with newly diagnosed VTE, including 389 patients with cancer, those with distant metastases had a higher risk of VTE (OR 19.8, CI 2.6–149) 136.

A multicentre retrospective study of VTE in hospitalized cancer patients reported an incidence of 10.3% in patients with advanced-stage cancer compared with 5.6% in patients with localized disease (P < 0.0005, OR 1.92, CI 1.21–3.04) 137, and these findings have been supported by other large studies in hospitalized cancer patients 138. Other studies in ovarian, colorectal, pancreatic, lung and breast cancer support the finding that advanced-stage disease increases the risk of cancer- associated VTE 139,140,141,142,143,144.
