VWF-cleaving protease (ADAMTS13) in premature infants

Background: Patients with thrombotic thrombocytopenic purpura (TTP) are deficient in von Willebrand factor (VWF)-cleaving protease, called ADAMTS13, and are prone to develop abnormal intravascular platelet aggregation leading to focal cerebral ischaemia. We speculated that low levels of ADAMTS13 are present in premature infants. This might result in platelet aggregation with subsequent ischaemia, vessel rupture and haemorrhage, and thus contribute to intraventricular haemorrhage and periventricular leucomalacia (IVH and PVL). Patients and methods: Nine preterm infants with gestational ages 23.7 to 30.9 (median 25.7) wk, and 10 healthy term control infants with gestational ages 36.9 to 39 (median 37.9) wk were included. Blood was sampled from the umbilical cord at delivery, and levels of ADAMTS13, VWF antigen and VWF collagen binding activity were analysed. Results: The mean ADAMTS13 level in preterm infants was lower than in the term infants, but the difference between the groups was not statistically significant. However, in the preterm group there was a positive correlation between ADAMTS13 and both gestational age (r=0.70,p=0.035) and birthweight (r=0.83,p=0.005). Three preterm infants had ADAMTS13 of 18-20%. One of these developed a germinal matrix haemorrhage and PVL, and this infant had the lowest measured ADAMTS13 of all. The levels of VWF antigen and VWF collagen binding activity were higher in the preterm infants. Conclusion: This pilot study showed that preterm infants have low levels of ADAMTS13. Enzyme substitution may be a therapeutic option if an association with IVH or PVL can be confirmed in larger patient groups.