Systemic thrombin generation in cancer patients is correlated with extrinsic pathway activation.
Costantini V. De Monte P. Cazzato AO. Stabile AM. Deveglia R. Frezzato E. Paolucci MC.
Istituto di Medicina Interna e di Medicina Vascolare, Universita degli Studi di Perugia, Italy. Vincenzo@unipg.it
Since the first report by Trousseau in 1865, several experimental and clinical studies have established that activation of coagulation is common in cancer. However, the biochemical basis of the activation of coagulation in cancer patients is still not completely understood. The current most accepted opinion is that initiation of coagulation in malignancy is driven primarily by activation of the extrinsic (tissue factor-dependent) pathway. In order to further prove that such a pathogenetic mechanism is actually involved in cancer patients, we correlated the plasma levels of activated factor VIIa (FVIIa), which represent a very small fraction of plasma FVII, with some well-established markers of systemic thrombin generation. Circulating FVIIa was measured using a prothrombin time-based assay that employs a truncated form of human recombinant tissue factor, while plasma levels of the thrombin-antithrombin complex, the prothrombin fragments 1 + 2 and D-dimer were determined by commercially available ELISA kits. The study was carried out in 37 patients with different types of cancer and 20 healthy controls. Plasma levels of FVIIa were significantly increased while those of FVII antigen (FVIIag) were decreased in cancer patients compared with controls. Furthermore, the FVIIa/ VIIag ratio was more than two-fold higher in cancer patients than in controls. In addition, an excess of thrombin generation was observed in cancer patients. Interestingly, a positive correlation between the FVIIa/VIIag ratio and the plasma levels of either D-dimer (Spearman's r = 0.325; P = 0.027) or prothrombin fragments 1 + 2 (r = 0.309; P = 0.034) was observed in cancer patients. In conclusion, our study further supports the hypothesis that the tissue factor/VIIa complex is the main determinant of coagulation activation in cancer patients. Large clinical studies will be necessary to determine whether FVIIa and the FVIIa/VIIag ratio are useful prognostic factors of thromboembolic events in cancer patients.
Soluble platelet endothelial cell adhesion molecule-1 (sPECAM-1) in inflammatory vascular disease, atherosclerotic vascular disease, and in cancer.
Blann AD. Wadley MS. Dobrotova M. Sanders P. Jayson MI. McCollum CN.
Department of Medicine, City Hospital, Birmingham, UK.
Cell surface adhesion molecule expression is likely to be important in inflammation, atherosclerosis and cancer, and soluble forms of many of these molecules are present in plasma. We measured levels of the soluble form of platelet endothelial cell adhesion molecule-1 (sPECAM) by ELISA in the serum of 77 patients with frank atherosclerosis, 69 patients with inflammatory connective tissue disease, and 39 patients with cancer. Each group of patients was controlled by an equal number of age- and sex-matched healthy subjects. There was no difference between sPECAM in patients with atherosclerosis and their matched controls or between patients with connective tissue disease and their controls. However, sPECAM levels were lower (16.6 +/- 5.0 ng/ml, mean +/- SD) in patients with cancer than in their controls (21.1 +/- 4.4 ng/ml, P < 0.001). No differences were found in sPECAM levels between the major subgroups of each type of disease, or as a result of factors such as age, sex or smoking in the controls. In contrast to levels of many other soluble adhesion molecules, levels of sPECAM are not altered in inflammatory or atherosclerotic vascular disease and therefore appear to have little relevance in these conditions. However, there may be significant differences in sPECAM levels in patients with low levels in cancer. Additional investigations are therefore justified.
The coagulation profile in hepatosplenic schistosomiasis.
El-Bassiouni NE. El Bassiouny AE. Hussein NA. El-Sayed HH. Ibrahim IM. Lotfy MG. Omran SA.
Haematology Department, Theodor Bilharz Research Institute, Giza, Egypt.
The biological activity of blood coagulation factors II, V, VII, VIII, IX, X, XI and XII, fibrinogen and prekallikrein was assessed in 15 healthy subjects and 60 patients with endemic Egyptian hepatosplenomegaly. The degree of liver disease was graded according to the Child-Pugh classification, the intensity of S. mansoni infection was monitored by determination of circulating schistosome immune complexes (CSIC) level using a monoclonal antibody and hemostasis activation was detected by measurement of hemostatic markers D-dimer and prothrombin fragment 1 + 2 (F1+2). Functional activity of antithrombin III, alpha2-antiplasmin and protein C as well as quantitative determination of plasma concentrations of alpha1-antitrypsin, C1 activator inhibitor and alpha2-macroglobulin were also carried out. The progressive deterioration of liver function which matched the severity of the disease and the intensity of schistosomal infection led to a reduction in anticoagulant proteins (decreases in antithrombin III and protein C) resulting in hypercoagulability and thrombin generation (increased F1+2) subsequently followed by consumption (prolongation of coagulation screening tests, thrombocytopenia, hypofibrinogenemia and decreased factor VIII resulting in hypocoagulability and secondary fibrinolysis (increased D-dimer and decreased alpha2-antiplasmin). A significant decline in fibrinogen and factors VII, XII and prekallikrein was detected in bleeders compared with ascitic patients. The decline in factor XII was closely related to CSIC high titers in all disease groups, but was not correlated to D-dimer or F1+2 concentrations. This suggests that circulating schistosome immune complexes may exert an inhibitory effect on contact factor XII which should be taken into account when considering the reasons for schistosomal coagulopathy and bleeding in hepatosplenic schistosomiasis.