Cancer patients are at high risk for venous thromboembolism (VTE). Laboratory parameters with a predictive value for VTE could help stratify patients into high-or low-risk groups. The cell adhesion molecule P-selectin was recently identified as risk factor for VTE. To investigate soluble P-selectin (sP-selectin) in cancer patients as risk predictor for VTE, we performed a prospective cohort study of 687 cancer patients and followed them for a median (IQR) of 415 (221-722) days.Main tumor entities were malignancies of the breast (n ‫؍‬ 125), lung (n ‫؍‬ 86), gastrointestinal tract (n ‫؍‬ 130), pancreas (n ‫؍‬ 42), kidney (n ‫؍‬ 19), prostate (n ‫؍‬ 72), and brain (n ‫؍‬ 80); 91 had hematologic malignancies; 42 had other tumors. VTE occurred in 44 (6.4%) patients. In multivariable analysis, elevated sPselectin (cutoff level, 53.1 ng/mL, 75th percentile of study population) was a statistically significant risk factor for VTE after adjustment for age, sex, surgery, chemotherapy, and radiotherapy (hazard ratio ‫؍‬ 2.6, 95% confidence interval, 1.4-4.9, P ‫؍‬ .003). The cumulative probability of VTE after 6 months was 11.9% in patients with sP-selectin above and 3.7% in those below the 75th percentile (P ‫؍‬ .002). High sP-selectin plasma levels independently predict VTE in cancer patients. Measurement of sP-selectin at diagnosis of cancer could help identify patients at increased risk for VTE. (Blood. 2008;112: 2703-2708)

Measurement of thrombin generation may help identify patients with cancer at high risk of VTE.

Background:The cell adhesion molecule P-selectin has an important role in the pathophysiology of thrombosis. The effect on venous thromboembolism (VTE) of increased circulating concentrations of soluble P-selectin (sP-selectin) and their association with the P-selectin variant Thr715Pro is still uncertain. Methods: This study was a case-control study of 116 patients with confirmed recurrent VTE and at least 1 event of unprovoked deep venous thrombosis or pulmonary embolism, and 129 age-and sex-matched healthy individuals. We measured sP-selectin by ELISA and P-selectin gene (SELP) variation by genotyping and sampled blood after a mean interval of 2.55 years after the most recent VTE event. Results: The mean (SD) sP-selectin concentration was higher in patients than in controls: 47.3 (15.0) g/L vs 36.8 (11.0) g/L, P <0.001. The unadjusted odds ratio (OR) for sP-selectin >55.1 g/L, representing the 95th percentile for controls, was 8.5 (95% CI, 3.7-23.3; P <0.001) and increased after adjustment for factor V Leiden, the prothrombin G20210A variant, increased factor VIII, and hyperhomocysteinemia (OR, 10.6; 95% CI, 4.1-31.2; P <0.001). Pro715 carriers were more prevalent among controls than patients (21.7% vs 14.7%).

Cancer patients are at high risk for venous thromboembolism (VTE), which represents an additional burden and a frequent cause of increased mortality. Laboratory parameters with a predictive value for VTE could help to assign a patient to a high or low risk group. In recent studies the cell adhesion molecule P-selectin was identified to be a strong risk factor for VTE. However, the role of soluble P-selectin (sP-selectin) in cancer-associated VTE is not known because up to now clinical data are not available. Therefore, we assessed sP-selectin plasma levels in cancer patients as a risk predictor for VTE and provide a report from the ongoing prospective observational CATS. Patients with newly diagnosed cancer or progression of disease who had no chemotherapy within the last three months were enrolled from October 2003 to October 2006 and followed prospectively via phone and mail. Occurrence of VTE and information on the patientś anti-cancer-treatment within the follow up period were recorded. VTE has always been confirmed by imaging. sP-selectin levels were measured with a highly sensitive ELISA. Kaplan Meier and Cox regression analysis were applied for statistical calculation. We included 687 patients (319 female/368 male, median age [IQR]: 62 [54–68] yrs) with malignant disease and followed them for a median observation period of 415 days. Main tumour entities were malignancies of the breast (n=125), lung (n=86), upper (n=30) and lower gastrointestinal tract (n=100), pancreas (n=42), kidney (n=19) and prostate (n=72). Furthermore, 80 patients had high-grade glioma, 73 lymphomas, 18 multiple myeloma and 42 other tumour types. Distant metastases were found in 268 patients at the time of recruitment. During the observation period VTE occurred in 45 patients (21 female/24 male, median age [IQR]: 62 [48–66] yrs). Elevated plasma levels of sP-selectin (cut-off level 53.1 ng/mL representing the 75th percentile of the total study population, 173 patients) [hazard ratio (HR): 2.5, 95% CI 1.4 – 4.6], surgery [HR: 3.9, 95% CI 1.8 – 8.5] and radiotherapy [HR: 3.2, 95% CI 1.6 – 6.4] were statistically significant risk factors for VTE in multivariable analysis including sP-selectin, age, sex, surgery, chemotherapy and radiotherapy. The cumulative probability of VTE after 6 months was 11.9% in patients with sP-selectin plasma levels above and 3.7% in those below the 75th percentile. In conclusion, high plasma levels of sP-selectin independently predict VTE in cancer patients. Measurement of sP-selectin at diagnosis of cancer would help to identify patients at increased risk for VTE.

Venous thromboembolism (VTE) is a frequent complication in cancer patients. Platelet activation is thought to be involved in cancer-associated VTE. Here, we determined the association between evolving markers of platelet activation (soluble P-selectin [sP-selectin], soluble CD40 ligand [sCD40L], thrombospondin-1 [TSP-1] and platelet factor-4 [PF-4]) and the development of cancer-associated VTE. A nested matched case-control study was applied within a cohort of 1779 patients with different types of cancer that had been included in the Vienna Cancer and Thrombosis Study (CATS), a prospective, observational study on patients with newly diagnosed or progressive cancer after remission. Primary endpoint is symptomatic VTE during a maximum follow-up of 2 years. Cases (patients who developed VTE during follow-up) were matched in a 1:2 ratio to controls without VTE during follow-up with respect to tumor type, stage and time of observation in the study. In total, 131 VTE cases were compared to 262 controls. In logistic regression analysis, only sP-selectin was associated with risk of VTE. The odds ratios (OR) per double increase of sP-selectin, sCD40L, TSP-1 and PF-4 were 1.66 (95% confidence interval: 1.17-2.35, p = 0.005), 1.04 (0.89-1.21, p = 0.635), 1.09 (0.90-1.32, p = 0.360) and 1.03 (0.87-1.21, p = 0.737), respectively. In conclusion, sP-selectin, but not sCD40L, TSP-1 or PF-4 were associated with risk of VTE in cancer patients in this nested case-control study.