Thromboembolic risks and complications in nephrotic children.

The identification of many biologic anomalies is progressively realized in nephrotic children, thanks to adult studies and to scientific advances. The number of anomalies and the intensity of alterations vary from one patient to another and during flare-ups in the same patient. Their severity is usually a function of the severity of the nephrotic syndrome (NS). The responsibility of each anomaly per se in triggering thrombotic complications is not yet known and today it is understood that the coexistence of several factors is necessary to induce these complications. Thus, the NS presents a true model because it can gather multiple thrombogenic anomalies. It might be more satisfying to characterize all of the mechanisms that could be responsible for a thrombosis rather than to assay all of the biologic components in one patient. When the main balances during the childhood NS are broken-pro- versus anticoagulant forces, pro- versus antifibrinolytic forces, platelet/vessel wall interactions-one cannot evaluate with accuracy the possible impact of acquired interrelations such as a decrease of antithrombin versus an increase of protein C. Among the present unknown factors, a major one is related to the effects, if any, of the proteinuric factor (recently discovered) on the vascular endothelium and the central question is: would it be capable of changing the thromboresistant phenotype to a thrombogenic one? No absolute correlation has been found between the many biologic abnormalities and the occurrence of thromboembolic (TE) complications. However, it is of great interest to have the best evaluation of the TE risks in nephrotic children. The criteria that are commonly used are: albuminuria, and plasma levels of fibrinogen and antithrombin. One can suggest adding to these criteria the D-dimer assay, a molecular marker of coagulation activation, and the factor V Leiden workup because it represents a genetic predisposition for TE complications. As far as prevention of TE complications is concerned, the standard but basic guidelines of nephrotic patients must be followed. Furthermore, vitamin K antagonists should be administered as soon as the risk criteria are gathered, but only after a careful evaluation of the benefits/risks ratio. As to the treatment of TE events, one should follow the present recommendations for children. A better future regarding prevention of TE accidents is based not only on the necessity of multicentric prospective studies but also on basic research that will allow discovery of the "primum movens" of childhood NS.