Thrombomodulin and von Willebrand Factor: Relation to Endothelial Dysfunction and Disease Outcome in Children with Acute Lymphoblastic Leukemia

Abstract

The severe endothelial dysfunction in children with acute lymphoblastic leukemia (ALL) can result from the disease itself, from treatment, or from other conditions (e.g. sepsis). The aim of this study was to determine the levels of markers of endothelial activation in children with ALL and to assess their potential prognostic value. Fifty-two children with ALL, 19 children with ALL 1–10 years after the completion of therapy, and 28 healthy children were studied. In children with ALL, there was a significant increase in thrombomodulin (TM) and von Willebrand factor (vWF) levels during the acute phase of the disease and during treatment. Children with an unfavorable outcome had higher levels of TM. In conclusion, severe endothelial dysfunction is present during the acute phase of ALL and during treatment and appears to result from the disease itself. Serum TM and vWF levels might represent additional, but not independent, prognostic markers in childhood ALL.

Von Willebrand Factor and Factor VIII Levels in Egyptian Children With Newly Diagnosed Acute Lymphoblastic Leukemia in Relation to Peripheral Blast Cells and Steroid Therapy

“…Any change in one factor is followed by a concomitant change in the other. 19 Our findings are supporting previous observations where increased levels of VWF antigen 6,8,9,[20][21][22] and FVIII 6 were reported at diagnosis of childhood ALL. It has been suggested that leukemic cells circulating in blood contain procoagulants or tissue factor either on the surface of the cells or within the cytoplasm.…”

von Willebrand Factor: More Than a Regulator of Hemostasis and Thrombosis

“…vWF abnormality has been reported in both hematologic malignancies and nonhematologic malignancies, including chronic lymphocytic leukemia [78], acute lymphoblastic leukemia [79], colorectal carcinoma [80], leiomyosarcoma [81], breast cancer [82] and prostate cancer [83]. In an experimental metastasis mouse model, vWF was observed to inhibit tumor metastasis [45].…”

Heparins that block VEGF-A-mediated von Willebrand factor fiber generation are potent inhibitors of hematogenous but not lymphatic metastasis

“…Among the different cancer types, the VTE incidence is especially high in malignant melanoma, occurring in approximately 25% of melanoma patients [3]. An association between an enhanced risk of thrombotic complications and an increase of von Willebrand factor (VWF) levels in plasma and tumor tissue of patients with distinct malignancies has been described by multiple clinical studies for specific malignancies [4–7]. VWF is a multimeric glycoprotein that has critical effects on hemostasis, angiogenesis, platelet recruitment [8] and thrombus formation [9].…”