Haemostatic measurements in childhood nephrotic syndrome

Abstract

Blood coagulation and platelet aggregation were assessed in children with nephrotic syndrome who were divided into the following groups: (1) relapse without treatment: (2) relapse on steroids; (3) early remission; (4) late remission and (5) steroid resistant. The renal histological findings were also recorded. Plasma anti-thrombin III (ATIII) levels were markedly reduced in groups 1 and 2, below normal in group 3 and were normal in groups 4 and 5. There was significant urinary loss of ATIII in groups 1 and 2 as well as in group 5. Plasma fibrinogen fluctuations exhibited the expected negative correlations with plasma ATIII. Reptilase time showed significant prolongation in groups 1, 2 and 3, and was near normal in groups 4 and 5. Platelet aggregation in response to arachidonic acid exhibited aggregation followed by disaggregation in groups 1, 2, 4 and 5, and was normal in group 3. Hyperaggregation in response to decreasing doses of ADP was noted in all patient groups as well as controls with no relationship to serum albumin levels. Aggregation responses to collagen and ristocetin were normal. It is concluded that: 1. The fluctuations in ATIII levels in childhood nephrotic syndrome are determined by the response to steroids and not by the renal histology per se. 2. An acquired fibrin polymerization defect (dysfibrinogenaemia) and an abnormality of the prostaglandin pathway of platelet activation, both reversible, are yet other haemostatic abnormalities in childhood nephrosis. 3. The discrepancies in the literature on haemostatic parameters, specially ATIII in childhood nephrosis, would not have arisen if their fluctuation in relation to steroid therapy as well as the renal histological features of nephrotic syndrome had been documented simultaneously.

Coagulopathy of Childhood Nephrotic Syndrome – A Reappraisal of the Role of Natural Anticoagulants and Fibrinolysis

“…The marked ele vation in the level of one natural anticoagu lant, protein C, in children, may partially compensate for the diminished level of the other (ATIII) [18]. It should also be pointed out that the majority of nephrotic children are steroid responsive, and, thus, the disease pro cess is characterised by phases of relapse and remission, while the majority of nephrotic adults are steroid-resistant, and their disease behaves in a way similar to the steroid-resis tant form of childhood nephrosis [11]. In this study, the level of tPA in both the relapse and remission of nephrosis was not markedly different from controls.…”

“…Our current study con firmed that during the relapse of nephrosis, there was the expected hyperfibrinogenaemia and the diminution of plasma AIII. This, in addition to the known increase in other coag ulation factors, V, VII, VIII, X [9] as well as higher platelet counts and activity [10,11 ] are markers of a greater tendency to thrombus formation. When remission sets under steroid therapy, it is clear that there is a marked reduction in fibrinogen, an increase in plasma ATIII, changes reflecting a reduced tendency towards thrombus formation.…”

“…In a previous study [23] fibrinolytic activity induced by ve nous occlusion was found to be higher in adult nephrotic patients than healthy controls. Ear lier investigators measured plasminogen, cuantiplasmin, ou-macroglobulin, ai-antitrypsin [1,3,5,7,9,11,14], but reported very con flicting results.…”

“…O f the patients in whom renal histopathology was determined, 14 patients with minimal change nephrotic syndrome were studied in both phases of the disease. Two blood samples were collected, as detailed previously [11]. The first sample was collected during relapse, while the patients were not on steroids, and the second sample, when the patients had been in the remission phase for 3 weeks and were still on steroids.…”

Nephrotic Syndrome and Pulmonary Artery Thrombosis

“…ATIII deficiency might be offset by increased serum alpha-2-macroglobulin. The discrepan cies in ATIII levels described in the literature have been attributed to steroid therapy [19]. Prophylactic use of ATIII has not been shown to be fully protective against thrombotic complications [20].…”