Von Willebrand factor:antigen and ADAMTS-13 level, but not soluble P-selectin, are risk factors for the first asymptomatic deep vein thrombosis in cancer patients undergoing chemotherapy

Budi Setiawan; Cecilia Oktaria Permatadewi; Baringin de Samakto; Ashar Bugis; Ridho M Naibaho; Eko Adhi Pangarsa; Damai Santosa; Catharina Suharti

doi:10.1186/s12959-020-00247-6

Von Willebrand factor:antigen and ADAMTS-13 level, but not soluble P-selectin, are risk factors for the first asymptomatic deep vein thrombosis in cancer patients undergoing chemotherapy

Thromb J. 2020 Nov 11;18(1):33. doi: 10.1186/s12959-020-00247-6.

Authors

Budi Setiawan¹, Cecilia Oktaria Permatadewi², Baringin de Samakto², Ashar Bugis², Ridho M Naibaho^{3

4}, Eko Adhi Pangarsa³, Damai Santosa³, Catharina Suharti³

Affiliations

¹ Division of Hematology and Medical Oncology, Department of Internal Medicine, Medical Faculty of Diponegoro University and Dr. Kariadi Hospital, Semarang, Indonesia. boedhi_smg73@yahoo.com.
² Department of Internal Medicine, Medical Faculty of Diponegoro University and Dr. Kariadi Hospital, Semarang, Indonesia.
³ Division of Hematology and Medical Oncology, Department of Internal Medicine, Medical Faculty of Diponegoro University and Dr. Kariadi Hospital, Semarang, Indonesia.
⁴ Fellow in Hematology and Medical Oncology, Department of Internal Medicine, Medical Faculty of Mulawarman University, Parikesit General Hospital, Kutai Kartanegara, Indonesia.

Abstract

Background: There is a high incidence of deep vein thrombosis (DVT) among cancer patients undergoing chemotherapy. Chemotherapy-induced vascular endothelial cell activation (VECA) is characterized by increased plasma levels of von Willebrand factor (vWF) and soluble P-selectin (sP-selectin), leading to the activation of endothelial cells and signaling cascades. The biological role of a disintegrin-like and metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS-13) is to control the activity of vWF and consequently the risk of thrombosis. The objective of this study was to investigate the roles of sP-selectin, vWF, and ADAMTS-13 as risk factors for the first episode of DVT in cancer patients undergoing chemotherapy.

Methods: This prospective cohort study was conducted at Dr. Kariadi Hospital, Indonesia, on 40 cancer patients. Prechemotherapy (baseline) and postchemotherapy sP-selectin, vWF antigen (vWF:Ag), and ADAMTS-13 plasma levels were determined with ELISAs before and 3 months after chemotherapy. The clinical characteristics of the patients, cancer type, cancer stage, chemotherapy regimen, ABO blood type, D-dimer level and Khorana risk score were also analyzed using logistic regression. Patients were observed for the possibility of developing DVT during chemotherapy.

Results: DVT was confirmed in 5 patients (12.5%) after a period of 3 months. In patients with DVT, sP-selectin and vWF were significantly higher while ADAMTS-13 was lower than in their counterparts. The levels of baseline vWF:Ag and ADAMTS-13, with cut-off points ≥ 2.35 IU/mL and ≤ 1.03 IU/mL, respectively, were found to independently predict the incidence of DVT. In the multivariate logistic regression analysis, the relative risk (RR) for DVT in patients with high vWF:Ag was 3.80 (95% CI 1.15-12.48, p = 0.028), and that for patients with low ADAMTS-13 was 2.67 (95% CI 1.22-23.82, p = 0.005). The vWF:Ag/ADAMTS-13 ratio and both vWF:Ag and ADAMTS-13 dynamics during treatment were also able to differentiate those with prospective DVT. However, sP-selectin and other covariates showed no statistical significance.

Conclusion: We found that prechemotherapy plasma levels of vWF:Ag ≥ 2.35 IU/mL and ADAMTS-13 ≤ 1.03 IU/mL are independent risk factors for DVT incidence among cancer patients.

Keywords: ADAMTS-13; Cancer; Chemotherapy; Deep vein thrombosis; sP-selectin; vWF.