Influence of fucoidans on hemostatic system.

Three structurally different fucoidans from the brown seaweeds Saccharina latissima (SL), Fucus vesiculosus (FV), and Cladosiphon okamuranus (CO), two chemically modified fucoidans with a higher degree of sulfation (SL-S, CO-S), and a synthetic totally sulfated octasaccharide (OS), related to fucoidans, were assessed on anticoagulant and antithrombotic activities in different in vitro experiments. The effects were shown to depend on the structural features of the compounds tested. Native fucoidan SL with a degree of sulfation (DS) of 1.3 was found to be the most active sample, fucoidan FV (DS 0.9) demonstrated moderate activity, while the polysaccharide CO (DS 0.4) was inactive in all performed experiments, even at high concentrations. Additional introduction of sulfate groups into fucoidan SL slightly decreased the anticoagulant effect of SL-S, while sulfation of CO, giving rise to the preparation CO-S, increased the activity dramatically. The high level of anticoagulant activity of polysaccharides SL, SL-S, and CO-S was explained by their ability to form ternary complexes with ATIII-Xa and ATIII-IIa, as well as to bind directly to thrombin. Synthetic per-O-sulfated octasaccharide OS showed moderate anticoagulant effect, determined mainly by the interaction of OS with the factor Xa in the presence of ATIII. Comparable tendencies were observed in the antithrombotic properties of the compounds tested.

Hypercoagulability as a prognostic factor for survival in patients with metastatic renal cell carcinoma.

BACKGROUND: In experimental systems, interference with coagulation can affect tumor biology. We suggested that abnormal coagulation could be a negative predictor for response to immunotherapy and survival among patients with metastatic renal cell carcinoma (MRCC). METHODS: To address this issue, retrospective analysis of 289 previously untreated MRCC patients entering on institutional review board-approved clinical trials was conducted between 2003 and 2006. In addition, two groups of MRCC patients with (n = 28) or without (n = 28) hypercoagulability were compared in a case-control study. Baseline and treatment characteristics were well balanced. RESULTS: Hypercoagulability was present at treatment start in 40% of patients. Median baseline fibrinogen was 6.2 mg/dl. Serious disorders were found in 68% of patients. Abnormal coagulation was strongly associated with a number of metastatic sites (2 and more metastatic sites vs. 0-1 (P = .001). Patients with high extent of hypercoagulability had significantly higher number of metastatic sites (P = .02). On univariate analysis, patients with hypercoagulability had significantly shorter overall survival than patients with normal coagulation; median survivals of 8.9 and 16.3, respectively (P = .001).Short survival and low response rate also were significantly associated with hypercoagulability in a case-control study. Median survival was 8.2 months and 14.6 months, respectively (P = .0011). Disease control rate (overall response + stable disease) was significantly higher in patients with normal coagulation: 71.4 versus 42.9% (P = .003). CONCLUSION: Hypercoagulability disorders were found to be prognostic factor for response rate to systemic therapy and survival in patients with MRCC.