Red blood cell aggregation in nephrotic syndrome

Patrick Ozanne, Robert B. Francis, Herbert J. Meiselman
<span title="">1983</span> <i title="Elsevier BV"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/3m6b6iknnva5hipfqmgwzuvyfq" style="color: black;">Kidney International</a> </i> &nbsp;
Red blood cell aggregation in nephrotic syndrome. Red blood cell (RBC) aggregation induced by fibrinogen is a major determinant of the non-Newtonian flow behavior of human blood and has been suggested as a possible contributing factor for thrombogenesis. Given the elevated fibrinogen levels and the high incidence of thrombotic accidents in nephrotic syndrome (NS), a study was designed to assess RBC aggregation in this disease. Three different aggregation assays were used: (1) changes in light
more &raquo; ... ansmission through static cell suspensions, aggregation half time (AHT); (2) low gravity centrifugation of blood in nearly vertical tubes, zeta sedimentation ratio (ZSR); (3) direct observation of dilute RBC suspensions, microscopic aggregation index (MAT). The results indicate that RBC aggregation, as measured by AHT and ZSR, is increased significantly in NS patients versus healthy controls (P < 0.001 for both methods); this increase was not a function of renal insufficiency. The AHT and ZSR data were well correlated with plasma fibrinogen levels (r = 0.75 and 0.84, respectively). No differences were observed with the MAI method, since with this technique the aggregation process reaches an asymptotic plateau for the range of fibrinogen found in NS. Implications of increased RBC aggregation and thus increased blood viscosity and flow disturbances on thrombogenesis are discussed. L'agregation erythrocytaire au cours du syndrome nephrotique. L' agrégation érythrocytaire induite par le fibrinogene est un determinant majeur du comportement non-Newtonien du sang humain et son role dans Ia thrombogenese a été suggéré. Etant donnés les taux élevés de fibrinogene et Ia grande fréquence des accidents thrombotiques dans le syndrome néphrotique (SN), une étude de l'agregation erythrocytaire a etC entreprise dans cette maladie. Trois diffCrentes techniques d'Ctude de l'agregation ont été utilisCes: (1) variations de Ia lumière transmise a travers une suspension cellulaire au repos, temps de demi-agrCgation (TDA); (2) centrifugation a faible gravité du sang dans un tube pratiquement vertical, rapport de sedimentation zeta (RSZ); (3) observation directe d'une suspension diluée, index d'agrCgation microscopique (JAM). Les résultats font apparaitre que l'agrégation erythrocytaire, mesurCe par le TDA et le RSZ, est significativement augmentCe chez les patients présentant un SN compares aux témoins sains (P < 0,001 par les deux methodes); cette augmentation n'est pas liée a l'insuffisance rCnale. Les donnes du TDA et du RSZ sont bien corrélées avec les taux de fibrinogene (r = respectivement 0,75 et 0,84). Aucune difference n'a été trouvé avec l'IAM car, par cette technique, l'intensité du processus d'agrégation atteint un plateau maximum pour les valeurs de fibrinogene observées dans le SN. Les implications de cette augmentation de l'agregation erythrocytaire donc de Ia viscosité sanguine et des modifications du flot sanguin sur Ia thrombogenese sont discutées. Deep vein thrombosis is involved in about 30% of the patients with nephrotic syndrome (NS) and, when located in renal veins, can dramatically worsen renal disease [1-31. Several factors leading to thrombosis in NS have been identified (for example, elevated levels of plasma fibrinogen and factors V and VIII, increased platelet counts), and there appears to be general agreement that NS induces a hypercoagulable state favoring the occurrence of thrombotic accidents [1] [2] [3] [4] [5] [6] [7] [8] [9] . Less attention has been given, however, to the possible role of enhanced red cell aggregation and thus altered blood rheology and blood flow as possible contributory factors in the development of thrombosis in this disease state. For example, increased blood viscosity could promote flow stasis in the venous circulation, thereby triggering the coagulation process by inducing local hypoxemia and endothelial damage [10] [11] [12] . Erythrocyte aggregation results from bridging between adjacent red cells by specific plasma proteins (fibrinogen and serum globulins) or colloids (high molecular weight dextran) adsorbed to the cell surfaces [13, 14] ; red blood cells (RBC) in isotonic saline without these proteins or colloids do not demonstrate cellular aggregation. The forces of aggregation due to macromolecular adsorption and bridging are countered by the forces of disaggregation due to mechanical shearing and electrostatic repulsion between the charged surfaces of the adjacent cells [13, 141. Thus, the degree of RBC aggregation depends on the properties of the red cells as well as their external milieu. Various experimental approaches to the study of RBC aggregation have been employed, including whole blood viscosity [15] [16] [17] , erythrocyte sedimentation rate (ESR) [18, 19] , zeta sedimentation ratio (ZSR) [19] [20] [21] [22] , direct observation of RBC suspensions under different shear conditions [23, 24], light transmission studies of cell suspensions [25], and microscopic measurement of dilute RBC systems [261. Given the elevated plasma fibrinogen concentrations found in NS, increased RBC aggregation could be anticipated; a review of the current literature, however, does not reveal studies specific for this rheologic parameter. This investigation was thus designed to measure the dynamics and steady state extent of RBC aggregation for NS RBC in autologous plasma, NS RBC in an isotonic dextran solution known to produce cell aggregation, and 0 Rh positive normal RBC in NS plasma. Our results indicate a significant increase in RBC aggregation for NS RBC in their own plasma; this aggregation showed a strong correlation with plasma fibrinogen concentration. NS RBC aggregatelike control cells in dextran solution and normal RBC in NS plasma exhibit increased aggregation. These results suggest that altered blood rheology caused by increased RBC aggregation may be of importance in the etiology of thrombosis associated with nephrotic syndrome. 519
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