Objectives
Tumour growth is associated with development of a hypercoaguable state and increased risk of thrombosis. In the absence of manifest thrombosis patients with solid tumours can present with abnormalities of blood coagulation, underlying a sub clinical hypercoagulable condition, characterised by varying degrees of blood-clotting activation. Factor VIII plasma concentration has been shown to be an independent and dose-dependant risk factor for venous Thromboembolism. Von Willebrand factor, the carrier molecule of circulating FVIII is expressed by vascular endothelial cells and in vitro observations indicate that chemotherapy induces endothelial damage with subsequent dysfunction. This study assessed FVIII, Protein C and Protein S response following multi modal therapy and surgery for oesophageal carcinoma.
Methods
Fifty oesophageal cancer patients were studied, (multimodal n= 25, surgery only, n=25), at time points 0 (pre-operatively, following the first and final cycles of chemoradiation, and on days 1, 3, 7, 14, 21 and 28 days, and at 3 and 6 months postoperatively. Blood samples were collected in tubes containing 0.109mmol/L trisodium citrate anticoagulant. Samples were centrifuged at 3000g for 20 minutes to obtain platelet poor plasma and stored in 5ml capped plastic tubes. Factor VIII levels were measured by one stage clotting assay with factor VIII-deficient plasma. Automated functional assays for Protein C and Protein S in plasma were performed. Results Factor FVIII levels were significantly elevated in the multimodal cohort following the 1st (p<0.008) and 2nd (p<0.001) cycles of chemoradiotherapy and at all time points following surgery, compared to baseline readings (p<0.001). Similar elevation was noted in the surgery only patients. No significant difference in factor FVIII levels between the multimodal group and surgery only patients was seen, except on day 21 (p < 0.04). Preliminary findings indicate a significant difference between the multimodal and surgery only cohorts in Protein C (0.74-1.32 IU/ml) levels (p < 0.05) at two timepoints.
Conclusion
Factor VIII serum levels are significantly elevated following preoperative chemoradiotherapy. The pattern of response post oesophagectomy did not differ between the two cohorts. Elevated levels are a risk factor for both primary and recurrent venous thrombolism. The precise pathogenetic mechanism and cause of this elevation remains to be elucidated. Further studies investigating Protein C activity and, relating Factor VIII to thrombosis and inflammation in the oesophageal cancer patient are required.