With great interest we read the recent article by Engür and Engür in which the authors suggest the instillation of platelet-rich plasma through an umbilical artery catheter for patent ductus arteriosus closure in preterm neonates.Reference Ali Engür and Engür ¹ Although this is an interesting approach, we feel that several technical and safety issues need to be discussed before pursuing this concept any further.

First, the clinical relevance of platelets in patent ductus arteriosus is unclear in humans. In contrast with the studies cited by Engür and Engür, others,Reference Shah, Hills and Waleh ² and weReference Sallmon, Weber and Hüning ³ have shown that platelet numbers were not associated with ductal closure in preterm infants. Although conditions known to cause platelet dysfunction were identified as risk factors for ductus arteriosus patency – for example, immaturity or sepsis – a clear association between impaired platelet function and patent ductus arteriosus has not been established in humans yet.

Second, cord blood-derived autologous platelet-rich plasma is theoretically appealing and might have more physiologic hemostatic properties in preterm infants, as compared with adult platelets.Reference Ferrer-Marin, Chavda and Lampa ⁴ However, there is a potential risk that these platelets’ function is altered by the same factors that impair function in the neonate with patent ductus arteriosus – for example, placental dysfunction, infection, and immaturity. In addition, cord blood is a very limited source for platelet-rich plasma, and volumes of more than 3–5 ml are hardly achievable. Furthermore, if infants are treated after a failed course of pharmacological ductus arteriosus closure (4th–7th day of life),Reference Hamrick and Hansmann ⁵ it would be necessary to store the platelet-rich plasma for several days. Storage of platelets is associated with a higher risk of infection and altered platelet function, which might impair the treatment success.

Third, application of platelet-rich plasma through an umbilical artery catheter placed in a retrograde manner in the distal aortic arch/proximal descending aorta close to the ductal ampulla does not imply that the majority of the plasma dose in fact reaches the ductal tissue versus the aorta. It is unclear whether sufficient local concentrations of growth factors in the ductus are achievable by placement of the catheter in the thoracic aorta next to the ductal ampulla or whether direct catheterisation of the ductus would be necessary, causing the need for radiological placement control. The latter approach has no major advantage over transcatheter device ductus arteriosus occlusion in small preterm infants.Reference Bentham, Meur and Hudsmith ^{6 ,} Reference Bass and Wilson ⁷

In addition, it would be necessary to have an umbilical artery catheter in place for several days. Because longterm indwelling umbilical artery catheters can cause serious complications such as catheter-related thromboembolic events, vasospasm, and infection,Reference Hermansen and Hermansen ⁸ it is questionable whether a possible patent ductus arteriosus treatment with platelet-rich plasma justifies an umbilical artery catheter in all preterm infants at risk for a patent ductus arteriosus in the absence of other indications for the catheter.

Furthermore, one has to consider potential systemic side effects of the platelet-rich plasma: Engür and Engür mention platelet-derived growth factor, transforming growth factor β, and vascular endothelial growth factor as potential mediators of platelet-rich plasma-induced ductal closure, all of which have been shown to be associated with the development of serious neonatal conditions such as bronchopulmonary dysplasia,Reference Witsch, Turowski and Sakkas ⁹ pulmonary hypertension,Reference Fleck ¹⁰ retinopathy of prematurity,Reference Jankov, Kantores and Belcastro ¹¹ or post-haemorrhagic hydrocephalus.Reference Merhar ¹²

We believe that a careful consideration of these aspects is mandatory before this theoretically appealing approach is transferred into clinical trials and application.