Correlation between Angiogenic and Coagulation-Fibrinolysis Factors and Stage of Disease in Non Hodgkin’s Lymphoma Patients.

BACKGROUND: Angiogenesis and activation of coagulation system in cancer patients are common and are thought to be unfavorable clinical parameters. Vascular endothelial growth factor (VEGF) and fibroblast growth factor (bFGF) are well-known angiogenic cytokines. The elevations of plasma fibrinogen and D-dimer level indicate coagulation and fibrinolysis activation. There may be links between angiogenic cytokines and coagulation - fibrinolysis factors in cancer. Possible specific interactions include releasing angiogenic factors, such as VEGF by activated platelets and binding of VEGF and bFGF to fibrin and fibrinogen resulting in an increase in endothelial cell proliferation.

AIM: The purpose of our study was: (a) to analyze relations of VEGF, bFGF serum levels and fibrinogen, D-dimer plasma levels with stage of disease according to Ann Arbor Staging System (AASS); (b) to evaluate correlation between serum levels of angiogenic cytokines and plasma levels of coagulation-fibrinolysis factors in non Hodgkin’s lymphoma patients.

MATERIAL AND METHODS: 52 non Hodgkin’s lymphoma patients (31 men, 21 women; median age 52,1 ± 14,7 years) in II, III or IV stage of disease according to AASS were assessed. In stage II were 15, in stage III- 10 and in stage IV- 27 persons. Serum VEGF, bFGF and plasma D-dimer levels were measured by enzyme-linked immunosorbent assay (ELISA). Plasma levels of fibrinogen were determined using Behring Coagulation System (BCS) equipment.

RESULTS: Plasma level of D-dimer was elevated in majority of patients, mean plasma D-dimer levels [ng/ml] were in stage II: 1654,3 ± 1301,5, in stage III: 1816,6 ± 1370,7, in stage IV: 2747,1 ± 1410,8. There was significantly higher D-dimer level in IV stage of disease in comparison to stage II and III. p<0,01. The mean serum VEGF levels [pg/mL] in following stages of disease were: in II: 387,4 ± 219,8, in III: 399,2 ± 235,0, in IV: 406,9 ± 308,8; mean serum bFGF levels [pg/mL] were: in II: 4,3 ± 2,9, in III: 4,6 ± 2,5, in IV: 4,4 ± 3,4; mean plasma fibrinogen levels [mg%] were: in II: 514,3 ± 198,7, in III: 518,0 ± 209,2, in IV: 495,4 ± 155,3). Differences in levels of VEGF, bFGF and fibrinogen between II, III and IV stage of disease were not statistically significant We observed positive linear correlation between VEGF and fibrinogen (r = 0,45; p<0,01) and between bFGF and fibrinogen (r = 0,52; p<0,05) and negative linear correlation between VEGF and D-dimer (r = −0,69; p<0,001) and between bFGF and D-dimer (r = −0,72; p<0,001).

CONCLUSIONS: Our study indicates that D-dimer level correlates with Ann Arbor Staging System in non Hodgkin’s lymphoma patients. Significant correlations between levels of VEGF/bFGF and fibrinogen/D-dimer suggest specific interactions between angiogenic and coagulation-fibrinolysis system.