A clinical and experimental study of platelet function in chronic renal failure

Abstract

and the Renal Uniit, Royal Infirmary, Cardiff SYNOPSIS Coagulation and platelet function studies were performed on 24 normal subjects and 29 patients with chronic renal failure due to various causes. Thrombocytopenia was uncommon in the uraemic patients but there was reduced platelet retention in glass bead columns and platelet aggregation with adenosine diphosphate (ADP) and thrombin was slower and less complete than normal. The rate of platelet disaggregation in uraemic patients was significantly reduced. The abnormalities tended to be more severe in more uraemic subjects. In normal subjects no interrelationships were observed between the various measurements of platelet activity. In patients there were significant interrelationships between the measurements of platelet aggregation with ADP and thrombin and between the measurements of aggregation and retention in glass bead columns. It is suggested that if a common pathway is involved in these reactions it is adversely affected in uraemia.Plasma coagulation defects were uncommon and present in only five of the uraemic subjects. Impaired prothrombin consumption apparently due to defective platelet function was present in half the patients but was not detected by a kaolin aotivation method. Although platelet coagulation function was activated during ADP aggregation and disaggregation in normal and uraemic subjects, it did not correlate in the latter with impairment of aggregation. It is suggested that aggregation and activation of platelet coagulant activity are not necessarily related aspects of platelet function. An effect of uraemic plasma on normal platelets was demonstrated by mixing experiments consistent with a humoral cause for the uraemic platelet defects.An abnormal bleeding tendency in patients with renal failure has been recognized for many years and has been attributed to several causes. Increased capillary fragility and thrombocytopenia have been described but recent work suggests that in uraemia the platelets do not function properly. In this condition they have been found to adhere abnormally to glass and to aggregate poorly with adenosine diphosphate (ADP) (Castaldi, Rozenberg, and Stewart, 1966) and thrombin Received for publication 31 May 1972. are due to the production of abnormal platelets or to the direct effect of humoral or other factors.In this paper we describe the results of a study of platelet function in chronic renal failure. The platelets of these patients were retained abnormally in glass bead columns and they aggregated poorly with ADP, and especially with tbrombin. Incubation of normal platelets with uraemic plasma resulted in an altered pattern of aggregation with ADP.

High platelet count as a link between renal cachexia and cardiovascular mortality in end-stage renal disease patients

“…Platelet reactivity plays a central role in thromboembolic events, especially in the setting of atherosclerotic cardiovascular disease, which is the leading cause of death in ESRD patients (3). In the early 1970s, Evans et al (37) described the platelet function abnormalities in uremic patients. Moreover, the high platelet reactivity determined in diabetic patients with coronary artery disease is associated with a higher risk of adverse cardiovascular events (38).…”

Role of endothelium-derived nitric oxide in the bleeding tendency of uremia.

“…It has also been documented that NO inhibits the process of platelet adhesion to vascular endothelium by activating soluble guanylate cyclase through a heme-dependent mechanism, thereby elevating intracellular cyclic GMP (22). Data are available, however, indicating that platelet adhesion is impaired in uremia (23)(24)(25). Possibly, therefore, L-NMMA, by inhibiting the biological effect of NO, eliminates a crucial factor responsible for the impaired platelet-vessel wall adhesion in uremia.…”

Influence of Inhibitor of Glucose Utilization on the Blood Platelet Function

“…Disturbance of the activation of plate let factor 3 [10] and of the aggregation [7] and adhesion [6] of platelets has been described by several groups and has been attributed by some to uremic toxins, such as phenolic compounds or guanidinosuccinate [9], Adenosine triphosphate plays an important role in platelet participation in hemostasis, and of course, glucose is the main substrate for adenosine triphosphate synthesis. Thus, inhibition of glycolysis in various tissues [3] includ ing the platelets [13] by phenolic acids, guanidinosuccinic acid, and the middle molecular 'inhibitor of glucose utiliza tion' (IGU) could explain the functional platelet defect of uremia.…”