Thromboembolism remains a significant cause of morbidity and mortality in newborns and young children who are sick. According to a recent review in the Journal of Thrombosis and Haemostasis, interactions between von Willebrand Factor (VWF) and its cleaving protease ADAMTS-13 could explain thromboembolism and pathological thrombosis in sick neonates and children.

Unprovoked, spontaneous thrombotic events such as pulmonary embolism and deep vein thrombosis are uncommon in healthy newborns and are far more likely to affect sick newborns. Abnormal interactions between VWF and ADAMTS-13 were recently identified as causal risk factors in the development of pediatric stroke and secondary microvascular disease.

“Based on published cumulative data it is evident that neonates demonstrate elevated rates of thromboembolism in the setting of acute illness,” the authors wrote.

The VWF/ADAMTS-13 interaction is essential for maintaining capillary flow, with ADAMTS-13 deficiency resulting in microcapillary thrombosis and thrombotic thrombocytopenia purpura (TTP). Both genetic deficiency of ADAMTS-13 and formation of anti-ADAMTS-13 antibodies result in TTP. Accurate measurements of VWF/ADAMTS-13 are needed in newborns and children.

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Unfortunately, assays used to detect VWF/ADAMTS-13 are technically limited. For example, in one VWF assay, interference from other antibodies can result in overestimation of VWF. Other assays exhibit poor sensitivity and high variation. Assays to detect ADAMTS-13 are often too technical for regular clinical use. Overall, many of these assays were developed for use in adult populations, and their performance in pediatric populations in which TTP and von Willebrand disease (VWD) can arise remains unstudied.

Coagulation occurs differently in newborns than in children. Moreover, studies assessing VWF/ADAMTS-13 interactions in neonates have used different study designs, measurements, and units. This results in contrasting findings with uncertain relevance for the characterization and diagnosis of diseases such as TTP and VWD.

“The interactions between VWF and ADAMTS-13 are of growing interest both for their contribution to normal hemostasis and as risk factors associated with pathologic thrombosis,” concluded the authors.

Reference

1. Katneni UK, Ibla JC, Hunt R, Schiller T, Kimchi-Sarfaty C. Von Willebrand Factor/ADAMTS-13 interactions at birth: implications for thrombosis in the neonatal period           [published online December 29, 2018]. J Thromb Haemost. doi: 10.1111/jth.14374