Sub-Clinical Activation of Thrombosis May Predict Survival in Cancer Patients

Background : Approximately 10% of newly diagnosed cancer patients will develop thromboembolic disease (TED) in the first year following diagnosis. We hypothesize that a subgroup of cancer patients at diagnosis will have subclinical changes in their coagulation system that will indicate increased risk for subsequent TED and/or predict increased adverse cancer outcome. Methods : We performed a prospective, non-interventional study of recently diagnosed cancer patients who were scheduled to start chemotherapy. We obtained a single plasma sample at the time of diagnosis and prior to therapy, and measured prothrombin 1.2 fragment (F1.2), a measure of thrombin activation, and plasma microparticle levels (MP), a measure of platelet, endothelial, and other cell activation. We reviewed subsequent clinical outcomes including survival and incidence of venous thrombosis. We accrued 22 patients with mean age 63 years (range 39 to 89; 20 males, 2 females), 12 with lung, 6 with colorectal, and 4 with head and neck cancer. Mean follow-up was 24 months (range 3 to 57). Plasma F1.2 and MP were assayed using commercially available ELISA kits. Results : T1.2 concentrations were significantly higher in the deceased subgroup (table 1; p<0.002), and in patients with venous thrombosis (table 2; p<0.05). MPs were not informative. Sensitivity and specificity for prediction of survival and venous thrombosis (table 3) were determined by comparing patients in highest quartile of levels with lower quartiles combined and by using threshold value of mean +2.5 SD’s determined by measuring levels in 8 healthy controls. | | Deceased Patients (N=7) | Alive Patients (N=15) | | ----------- | ----------------------- | --------------------- | --------- | | Mean +/- SD | Median | Mean +/- SD | Median | p-value | | F1.2 (pM) | 436+/-214 | 355 | 121+/-117 | 105 | <0.002 | | MP (nM) | 10+/-10 | 3 | 8.8+/-2.8 | 2.8 | Not Significant | Table 1. Survival: F1.2 and MP (Mann-Whitney) | | Thrombosis (N=4) | No Thrombosis (N=18) | | ----------- | ---------------- | -------------------- | ---------- | | Mean +/- SD | Median | Mean +/- SD | Median | p-value | | F1.2 (pM) | 368+/-267 | 313 | 189+/-191 | 163 | <0.05 | | MP (nM) | 5.9+/-5.3 | 3.9 | 9.8+/-15.6 | 2.7 | Not Significant | Table 2. Venous Thrombosis: F1.2 and MP (Mann-Whitney) | | >mean + 2.5 SD’s | Highest Quartile | | | ---------------------- | ---------------- | ---------------- | --- | ---- | | | MP | T1.2 | MP | T1.2 | | Death SENSITIVITY | 43% | 43% | 43% | 71% | | Death SPECIFICITY | 87% | 100% | 87% | 93% | | Thrombosis SENSITIVITY | 25% | 25% | 25% | 50% | | Thrombosis SPECIFICITY | 78% | 89% | 78% | 78% | | | | | | | | Table 3. Sensitivity/Specificity Analysis Conclusion: T1.2 levels measured at time of diagnosis of cancer correlated with increased mortality and development of venous thrombosis. MP levels were not informative, possibly due to the limited size of the study population. Additional studies are needed to elucidate whether these biomarkers may be useful in identifying a higher risk population for death and/or venous thrombosis, and to help guide enhanced therapy for such higher risk patients. Disclosures No relevant conflicts of interest to declare.