The role of ADAMTS‐13 and von Willebrand factor in cancer patients: Results from the Vienna Cancer and Thrombosis Study

Abstract

Cancer is associated with increased risk of developing venous thrombosis. Cancer patients were studied for ADAMTS‐13 and VWF levels and occurrence of venous thrombosis. Increased VWF in cancer patients is associated with a higher risk of venous thrombosis. Low levels of ADAMTS‐13 and/or increased VWF in cancer patients are associated with worse survival. Background Cancer‐associated venous thromboembolism (VTE) is an important complication in the course of a malignant disease. Low ADAMTS‐13 (a disintegrin‐like and metalloproteinase with thrombospondin type 1 motif 13) and increased von Willebrand Factor (VWF) levels in cancer patients have been described numerously. Objectives Investigation of the influence of ADAMTS‐13 and VWF on the probability of VTE and survival in malignancy. Patients/Methods In the framework of the ongoing prospective Cancer and Thrombosis Study (CATS) ADAMTS‐13 activity and VWF antigen levels were investigated in cancer patients. Results In total, 795 patients with various tumor types (364 female/431 male, median age 62 years) were included; of those, 56 developed VTE and 359 patients died during a median follow‐up time of 730 days. The hazard ratio (HR) of VTE per doubling of VWF level was 1.56 (95% confidence interval [CI] 1.13‐2.16) in multivariable competing risk analysis. ADAMTS‐13 levels showed no correlation with the incidence of VTE in univariate competing risk analysis. The HR of mortality per doubling of VWF level was 1.46 (95% CI 1.28‐1.66) and per SD increment of ADAMTS‐13was 0.90 (95% CI 0.81‐1.00) in multivariable Cox regression analysis. Patients with VWF >75th percentile and concomitant low (<25th percentile) or medium (25‐75th percentile) ADAMTS‐13 values had the highest probability of mortality (HR 4.31 and 4.75, respectively). Conclusions High VWF levels were significantly associated with the risk of developing VTE in cancer patients, whereas ADAMTS‐13 was not. Low ADAMTS‐13 and increased VWF levels were independently associated with worse overall survival.

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

“…Similar studies were conducted by Pepin et al 35 from France and Obermeier et al 36 from Austria: these authors reported different perspectives on the role of ADAMTS-13 in relation to high vWF:Ag. Previous studies have shown that the activity and level of ADAMTS-13 are slightly lower in cancer patients than in healthy controls.…”

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

“…We hypothesized several possible mechanisms for this phenomenon, including impaired protein synthesis in the liver or endothelial dysfunction associated with direct chemotherapy toxicity and consumption by increased vWF substrates. 36,43 Various oncogenes have also been found to regulate the expression of extracellular proteinases, including matrix-degrading metalloproteinases, which can directly disrupt ADAMTS-13 activities. 43 Both the mechanisms of declination and to what extent ADAMTS-13 contributes require further study using different approaches.…”

Thrombotic microangiopathy in cancer patients

“…Одним из факторов патогенеза ТМА у онкологических больных будет активация эндотелия опухолевыми клетками (опосредованная тканевым фактором, цистеиновой протеазой и другими эффекторами), что ведет к высвобождению мультимеров vWF, активации ADAMTS13, а затем, вследствие интенсивного потребления, к истощению уровня и активности ADAMTS13 [78].…”

“…Следует особо отметить, что при увеличении уровня и активности vWF даже нормальные и субнормальные уровень и активность ADAMTS13 не будут способны в достаточной мере скомпенсировать повышенную активность vWF. Другими словами, важным фактором патогенеза ТМА является не только увеличение уровня vWF и снижение ADAMTS13 в абсолютных цифрах, но именно соотношение ADAMTS13/vWF, дисбаланс которого возникает у онкологических больных и это может служить одним из прогностических факторов [78].…”