Treating Venous Thromboembolism in Patients With Cancer

Caroline Piatek; Casey L O'Connell; Howard A Liebman


Expert Rev Hematol. 2012;5(2):201-209. 

In This Article

Predicting the Risk of Developing VTE

Based on known risk factors, a simple model for predicting chemotherapy-associated VTE in ambulatory cancer patients was developed by Khorana et al.[37] The patient population from this study was previously described as part of the Awareness of Neutropenia in Chemotherapy Study Group Registry, an observational study of cancer patients initiating a new chemotherapy regimen.[38] The study included patients with breast, colorectal, lung, gynecologic, gastric, pancreatic and lymphoma who were to receive systemic chemotherapy. Other cancer sites made up the 10% of remaining patients. A derivation cohort of 2701 patients was used to develop the risk model, and an independent cohort of 1365 patients was used to validate the model. The five predictive variables identified include cancer site, elevated prechemotherapy platelet count, anemia or use of red blood cell growth factors, elevated prechemotherapy leukocyte count and elevated BMI. Very-high-risk cancer sites (pancreatic and gastric cancer) made up 2% of the derivation cohort and 1.4% of the validation cohort. Over a median follow-up period of 73 days, the rates of VTE in the derivation and validation cohorts, respectively, were 7.1 and 6.7% in patients with a risk score ≥3 out of 6 points, 1.8 and 2% in those with a score of 1–2, and 0.8 and 0.3% in those with a score of 0.[37]

This risk model was subsequently validated in another cohort of cancer patients and expanded with two additional laboratory markers, soluble P-selectin (sP-selectin) and D-dimer ( Table 1 ). Both sP-selectin and D-dimer have been previously identified as independent predictors of cancer-associated VTE in the Vienna Cancer and Thrombosis Study (CATS).[39] P-selectin is an adhesion molecule found in the Weibel–Palade bodies of endothelial cells and α-granules of platelets and is recognized to play a role in thrombosis.[40] When sP-selectin level is elevated above the 75th percentile, it is associated with a 2.6-fold increased risk of VTE compared with patients with sP-selectin levels below the upper quartile.[41]D-dimer is a degradation product of cross-linked fibrin and, when elevated, can indicate the activation of coagulation and fibrinolysis. In a study of 821 patients with newly diagnosed cancer or progression of disease, D-dimer levels were significantly higher in those patients that developed a VTE during the median follow-up period of approximately 17 months.[42]

The patient population used to generate the expanded risk model consisted of 819 patients from Vienna CATS enrolled at the time of newly diagnosed cancer or progression of the disease. The median follow-up was much longer in this study than in that of Khorana et al. (21.4 months vs 73 days). The authors applied the model developed by Khorana et al. to these patients with several modifications based on the differences in cancer type represented in the Vienna CATS patient population. Primary brain cancer, kidney cancer and multiple myeloma cumulatively made up one-fifth of the Vienna CATS patients. Primary brain tumors were added to the very-high-risk category. Kidney cancer and multiple myeloma were added to the high-risk category. Of note, head and neck cancers were not included in this study. The expanded model included one point for each elevated sP-selectin and D-dimer, with cut-off points determined by the previously mentioned studies.[41,42] This model was better able to stratify high-risk patients from low-risk patients with the cumulative probability of VTE of 35% at 6 months with a high-risk score (≥5 points) and 1.0% with a low risk score (0 points) ( Table 2 . Yet the application of this extended risk-assessment tool is limited by the fact that the sP-selectin assay is not routinely performed in clinical centers and that there is significant variability of D-dimer assays employed.


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