Increased Tendency of Venous Thrombosis in Patients with Hematology Malignancies with Over-Expression of TF and Heparanase.

Patients with hematology malignancies have an increased risk of deep vein thrombosis and lower limb lymphedema which is often increased by an intensive chemioterapy or by a myeloablative regimen that often requires multiple platelet-transfusion. Hypercoagulability in cancer patients is associated to phlogosis (the mRNA levels for pro-inflammatory cytokines IL-1, IL-8, LIF, MIP2-alfa were also increased), dysprotidemia, age, bed rest, cancer cell prothrombotic properties (including activation of blood coagulation), impairment of fibrinolytic pathways, alterations of endothelium, increase of the clotting activation markers, and up-regulation of such genes as those coding for transcription factors (c.fos EGR-1, ETO101, c-Myc, Fry-1), over-expression of TF, over-expression of heparanase and formation of a fibrin coat.

Both the over-expression of TF and the formation of the TF/VIIa complex induce multiple cellular responses that include proteolytic activity, calcium fluxes, p44/p42 mitogen activated protein kinase phosphorylation, and generation of thrombin. The over-expression of heparanase increased angiogenesis, tumor growth, and metastasis.

To investigate the incidence of VTE (venous thromboembolism), and DVT (deep venous thrombosis) in patients with hematology malignancies we have studied 22 patients: 7 with a myeloproliferative disorder (5 with polycythemia rubra vera, 2 with essential thrombocyhemia), 4 with lymphoma, and 11 with leukemia. No patients had suffered from venous or arterial thrombosis before diagnosis of cancer, 14 patients had a first symptomatic thrombosis occurring five months after diagnosis, 4 after starting cytoreductive treatment, 5 patients had a recurrent thrombosis during remission of their disease, no significant differences were found in the cumulative incidence of thrombosis after stratification of the patients respectiely to sex, age, and transient factors (surgery, immobilization, cateteri). For the diagnosis of DVT: CUS (compression ultrasonografy) was performed in all patients combined with D-Dimer levels. Besides we have studied the levels of TF and Heparanase (anti-heparanase antibodies IgG 2BK: HP3/17). The incidence of VTE/DVT has been demonstrated to be associated with the highest levels of TF and Heparanase.