The vWF/ADAMTS13 Ratio as a Potential Marker of Endotheliopathy in Malignancies.

Abstract

Background: Endothelial activation and thromboinflammation play an important role in cancer-associated thrombosis. An imbalance between von Willebrand factor (vWF) and its physiological regulator ADAMTS13 may reflect the development of a prothrombotic endothelial state in patients with malignancies. However, the dynamics of the vWF-ADAMTS13 axis during chemotherapy and thromboprophylaxis remain insufficiently characterized. Objectives: To characterize the vWF-ADAMTS13 axis as a potential laboratory marker of endotheliopathy in patients with gynecologic malignancies and to assess its dynamics during chemotherapy and thromboprophylaxis with low-molecular-weight heparin (LMWH). Materials and Methods: This prospective comparative study included 74 patients with stage I-III gynecologic malignancies undergoing chemotherapy after surgical treatment. Group I comprised 34 patients with a history of thrombotic complications (VTE), including 23 patients with ovarian cancer and 11 with cervical adenocarcinoma. Group II included 40 patients without previous VTE, including 20 patients with ovarian cancer and 20 with cervical adenocarcinoma. The control group consisted of 25 healthy women. Plasma vWF levels, ADAMTS13 antigen and functional activity, ADAMTS13 inhibitor levels, and the vWF/ADAMTS13 ratio were assessed before chemotherapy and after 1-2 chemotherapy cycles. Patients in Group I additionally received thromboprophylaxis with nadroparin calcium. Results: Before chemotherapy, an imbalance of the vWF-ADAMTS13 axis was observed in patients with malignancies compared with healthy controls and was most pronounced in patients with a history of thrombosis. The vWF/ADAMTS13 ratio was 0.65 in controls, 1.02 and 0.84 in patients without previous VTE with ovarian and cervical cancer, respectively, and 1.59 and 1.34 in the corresponding subgroups with a history of thrombosis (p < 0.05). After 1-2 chemotherapy cycles, the vWF-ADAMTS13 axis showed a further shift toward imbalance, characterized by increased vWF levels, decreased ADAMTS13 antigen levels and functional activity, and increased ADAMTS13 inhibitor concentrations. The vWF/ADAMTS13 ratio increased to 2.04 in patients with ovarian cancer and to 1.65 in those with cervical cancer and a history of thrombosis. In Group I, the subsequent assessment following chemotherapy and LMWH thromboprophylaxis demonstrated partial reversal of these changes: ADAMTS13 antigen levels increased, while vWF levels and ADAMTS13 inhibitor concentrations decreased, and the vWF/ADAMTS13 ratio declined from 2.04 to 1.30 in ovarian cancer and from 1.65 to 1.14 in cervical cancer. Conclusions: The vWF-ADAMTS13 axis is markedly altered in patients with gynecologic malignancies, including those without previous VTE, with the most pronounced imbalance observed in patients with a history of thrombosis. The post-chemotherapy assessment demonstrated a further shift toward imbalance, whereas the subsequent assessment following chemotherapy and LMWH thromboprophylaxis in Group I showed partial reversal of these changes. The vWF/ADAMTS13 ratio may represent a potential integrative and dynamic marker of endothelial-hemostatic imbalance in patients with gynecologic malignancies.