Alterations in serum prothrombotic markers induced by treatment with bevacizumab-based chemotherapy regimens

Abstract

15034 Background: An increase in thrombotic events has been observed during treatment with chemotherapy and bevacizumab in patients with metastatic carcinoma. A better understanding of the effect of bevacizumab on haemostasis is necessary to determine the true thrombogenic potential of this drug. Methods: 10 patients with metastatic colorectal cancer (mCRC) commencing first line or salvage chemotherapy with bevacizumab were included in this prospective trial. Plasma samples were drawn at baseline, after the first cycle of treatment containing chemotherapy alone and after the second cycle containing chemotherapy plus bevacizumab. The study evaluated alterations of markers of procoagulant activation, natural anticoagulants, endothelial cell and platelet activation. The markers analysed were: prothrombin time (PT), activated partial thromboplastin (aPTT), D-Dimer (D-Di), fibrinogen (Fibn), factor VIII (FVIII), activated protein C (APCR), protein C (PC), free protein S (fPS), soluble P-selectin (sP-sel), platelet count (plt), von Willebrand factor antigen (vWF:ag) and von Willebrand factor activity (vWF:act). Results: The mean basal levels of D-Di and Fibn were increased above the normal range and remained elevated throughout the course of treatment analysed. Significant differences were noted in the levels of PC, plt and vWF:ag between the basal values and post-cycle 2 results (p=0.003, p=0.007 and p=0.05 respectively). The mean pre-treatment and post-chemotherapy cycle 1 levels of sP-sel were also above the normal range but were in the normal range after the second cycle. A thrombotic event occurred in one patient after the second cycle of chemotherapy. Conclusion: Metastatic CRC is associated with a prothrombotic state. A reduction in natural anticoagulation (PC) and increased vascular activation (vWF:ag) was seen in patients treated with bevacizumab. Platelet activation, as demonstrated by P-selectin levels was reduced with chemotherapy and normalised with the addition of bevacizumab. These data not only support prior observations of the prothrombotic state in cancer patients treated with chemotherapy, but also provides in vivo evidence of the mechanisms of the procoagulant effect of bevacizumab-based chemotherapy. No significant financial relationships to disclose.