parking unrelated ticklers......
heparin itself is angiogenic, and, indeed, much of the effort to inhibit angiogenesis is based on attempts to block the interaction of heparans with VEGF and/or bFGF.
endogenous adenosine has been proposed as a cofactor for heparin-mediated angiogenesis.
vitronectin and anti-alphaVbeta3.
Blood Coagul Fibrinolysis 1994 Jan;5 Suppl 1:S19-23; discussion 59-64
The hypercoagulable state in cancer patients: evidence for impaired
thrombin inhibitions.
Falanga A, Ofosu FA, Delaini F, Oldani E, Dewar L, Lui L, Barbui T
Department of Haematology, Ospedali Riuniti Bergamo, Italy.
Activation of prothrombin and the subsequent reactions of thrombin with its substrates and its major inhibitors, antithrombin III
(AT III) and heparin cofactor II (HC II), likely reflect both intravascular and extravascular coagulation. Several studies have
reported increased in vivo coagulation in cancer. Whether the increased thrombin production in malignancy is accompanied by
a corresponding increase in thrombin inhibition is unknown. This study quantified prothrombin fragment 1 + 2 (F1 + 2),
thrombin-AT III (TAT), thrombin-AT III-vitronectin (TAT.V), and thrombin-HC II-vitronectin (THCII.V) in the plasmas of
healthy volunteers (n = 37); patients with localized solid tumours before treatment was initiated (n = 39); and five patients with
non-Hodgkin's lymphoma, both before and during weekly chemotherapy. Two of the five non-Hodgkin's lymphoma patients
developed deep venous thrombosis (DVT) during chemotherapy. In normal plasma, where the concentrations of the four
parameters likely reflect haemostasis, the sum of TAT, TAT.V and THCII.V was 61% that of F1 + 2, compared with 30% in
cancer plasmas. In addition, the mean +/- SEM of F1 + 2 in the plasmas of cancer patients (1.56 +/- 0.09 nM) was
significantly elevated (P < 0.001) when compared with healthy volunteers (0.89 +/- 0.06 nM). Eight weeks of chemotherapy
increased the F1 + 2 and the binary TAT in plasmas of the non-Hodgkin's lymphoma patients by approximately 1.5- and
2.9-fold, respectively. Thus, increased prothrombin activation in cancer patients, without corresponding increases in
concentrations of thrombin-inhibitor complexes, raise the possibility that a significant portion of the thrombin generated in vivo
escapes inhibition in cancer and contributes to the high risk of DVT in malignancy.
Oncology 1992;49(6):426-30
Latent coagulation disorders evaluated by the assay of plasma
thrombin-antithrombin III complexes in a large series of 'solid tumours'.
Bartoloni C, Guidi L, Tricerri A, Patriarca F, Pili R, Cursi F, Canetta M, Cappelli A, Vangeli M, Salvati F, et al
Istituto di Clinica Medica, Universita Cattolica del S. Cuore, Roma, Italia.
Coagulation disorders are frequently detected in patients affected by different tumours even though clinical symptoms occur in a
very small percentage of such subjects. Coagulation processes are probably involved in the mechanism of metastatic spread.
We assayed the plasma levels of thrombin-antithrombin III (TAT) complexes in a group of 276 patients with several tumours in
different stages in order to achieve a better understanding of the complex interactions between coagulation disorders and either
tumour growth or metastatic spread. High levels of TAT complexes were found in 51% of localized, 66.3% of metastatic and
58.3% of patients with no evidence of disease; a statistically significant difference was observed comparing metastatic cancer
either with localized (p < 0.00015) or with free-of-disease (p < 0.004) groups. Gastrointestinal tract neoplasms showed higher
levels of TAT complexes in the metastatic than in the localized group. No difference was seen between small-cell and
non-small-cell lung-localized cancer. Our results confirm the frequent coexistence of cancer and subclinical blood coagulation
disorders. The evidence of higher levels of TAT complexes in metastatic cancer than in the other groups could be related to the
mechanisms involved in tumour spread. |
