Patients with cancer are at high risk for developing venous thromboembolism (VTE), and the risk is much higher if the patient has higher von Willebrand factor (vWF) and ADAMTS-13 activity levels, according to results from a case-control study published in the Journal of Thrombosis and Haemostasis by Marion PÃ©pin, from the HÃ´pital Louis Mourier in France, and colleagues. Adding these factor level measurements to a clinical prediction tool for VTE increased the tool's predictive value, as well.
Dr. PÃ©pin and co-authors analyzed data from an ongoing, multi-center, international, prospective cohort study of consecutive ambulatory patients with recently diagnosed cancer to investigate the predictive value of parameters for the occurrence of VTE.
Adult patients were included in the study if they had a histologically confirmed diagnosis of solid organ cancer stage III or IV or tumor progression after a remission period. Chemotherapy was initiated within three months prior to study inclusion and up to one week after inclusion, though patients receiving therapeutic anticoagulant treatment or adjuvant chemotherapy were excluded.
The study included 160 patients: 20 cases (patients with cancer and VTE) and 140 controls (patients with cancer but no VTE). The mean patient age was 61.9 years, and the majority of patients were male (68.1%; n=109). Within the case cohort, most patients developed VTE after a median of 2.2 months, and VTE was symptomatic in a majority of these patients (55%).
Patients' risk for VTE was calculated using the Khorana score and the Vienna Cancer and Thrombosis Study (CATS) score, which are clinical prediction tools that incorporate the following biomarkers that are associated with VTE risk: soluble P-selectin (sP-sel), factor VIII, and D-dimer or prothrombin fragment 1 + 2 (F1 + 2).
Once risk scores were calculated, patients were stratified as:
- Low risk: score = 0
- Intermediate risk: score = 1-2
- High risk: score = â‰¥3
See the TABLE for ADAMTS-13 and vWF levels in both patient cohorts.
ADAMTS-13 (activity or antigen) levels were in the normal range (50-150% and 400-1200 ng/mL, respectively) and not significantly different between cases and controls, even after adjustment for vWF levels. However, vWF levels were increased in all patients, and VTE patients had higher levels (326 IU/mL) compared with cancer patients without VTE (242 IU/mL; p=0.02). This difference remained significant when adjusting for ADAMTS-13 levels (p=0.02).
High vWF levels (>290 IU/mL) were found to be independently associated with a higher risk of VTE (odds ratio [OR] = 4.3; 95% CI 1.6-11.7; p=0.004). "Interestingly, vWF levels did not improve the scores in multivariate analysis, maybe due to a confounding parameter," the authors added.
vWF levels, but not ADAMTS-13 activity and antigen levels, corresponded with the biomarker levels used in the Khorana and Vienna CATS scores. However, when F1 + 2 levels (OR=5.7; 95% CI 1.9-19.6) were added to the Khorana prediction score measurements, the tool's predictive value significantly improved. The Vienna CATS scores also improved when vWF or F1 + 2 levels were added (OR=4.3; 95% CI 1.6-11.8). Adding ADAMTS-13 activity and F1 + 2 levels significantly improved both the Khorana (OR=5.0; 95% CI 1.2-23.5; p=0.03 and OR=6.8; 95% CI 2-25.9; p=0.002, respectively) and the Vienna CATS scores' ability to predict future VTE (OR=5.8; 95% 1.4-28.2; p=0.02 and OR=4.0; 95% CI 1.2-5.5; p=0.03, respectively).
Although Dr. PÃ©pin and colleagues noted that there was a potential bias in the rates of VTE in the study's design (as each patient with cancer who developed VTE was matched with seven patients with cancer without VTE), "in our population the Khorana score did not discriminate between patients with and without VTE."
"Our study demonstrates that investigation of hemostasis biomarkers contributes to distinguishing between patients with different VTE-risk categories, which is an essential step toward targeted thromboprophylaxis in patients with cancer," the authors concluded.
Tests to measure ADAMTS-13 are not widely available – mostly due to standardization issues – which could impact the real-world use of these findings. The small patient population is also a limitation. The researchers recommend future larger, prospective studies to define the potential role of ADAMTS-13 in the development of cancer.
|TABLE. ADAMTS-13 and vWF Levels in Study Participants|
|242 IU/mL||2.7 (95% CI 1.1-6.5)||
|81%||1 (95% CI 0.9-1.1)||
|564 ng/mL||1 (95% CI 0.9-1.1)||
|0.44||0.5 (95% CI 0.2-1.1)||
|0.15||4.8 (95% CI 0.2-133)||
|vWF = von Willebrand factor; OR = odds ratio|