LAUSR

Moreira et al. describe a fascinating case of a 5-year-old who developed microangiopathic hemolytic anemia (MAHA) a week after presentation with idiopathic systemic capillary leak syndrome (SCLS) and propose ADAMTS-13 loss in the third-space fluid as the cause of MAHA [1]. It would, however, be useful if the authors could provide the values of vascular endothelial growth factor (VEGF) and von Willebrand factor (VWF) levels in this patient during the illness episode before this conclusion is made. Endothelial dysfunction is well known to cause very high levels of both VEGF and VWF, which has been shown in many experimental studies; these markers are used as markers for endothelial activation and altered function [2,3]. It is possible that high levels of VEGF contributed to the SCLS in this patient and the decrease in ADAMTS-13 is the result of continuous enzyme activation from the breakdown of the very large amounts of VWF released. In addition, Lesterhuis et al. have suggested a causative role for VEGF in systemic capillary leak syndrome in two adult patients [4]. Baseline plasma VEGF levels have also been noted to be very high in several SCLS patients by another group [5]. In support of this concept, fresh frozen plasma (FFP) infusions and immunoglobulin treatments have not helped in this patient’s capillary leak symptoms, because they would not reduce VEGF levels. In addition, because patients with acute presentation of congenital thrombotic thrombocytopenic purpura (TTP) usually would require more than two FFP infusions for recovery, it is unlikely that FFP could completely normalize the extravascular loss of ADAMTS-13 (although it may improve the plasma levels). However, replacement of ADAMTS-13 to break down the large amount of plasma VWF multimers could certainly be considered effective in improving MAHA features. This case also illustrates a very interesting aspect of capillary leak syndromes that is commonly associated with sepsis. If a degree of ADAMTS-13 loss occurs in the extravascular space in patients with sepsis (as in this case), it is possible that replacement of this enzyme (via FFP or recombinant molecule) may improve the thrombocytopenia and microvascular dysfunction (and subsequent organ impairment) that are commonly noted in these patients [6]. In summary, it is possible that ADAMTS-13, the levels of which decrease in clinical scenarios of extreme endothelial activation and capillary leak syndromes instigated by high VEGF levels, may prove to be a potential therapeutic strategy in preventing some of the complications in this syndrome.