Studies on blood platelets in uraemia

The bleeding tendency in uraemia has been under investigation in recent years. It has been attributed to vascular fragility, thrombocytopenia and abnormalities in plasma coagulation factors. A qualitative platelet defect has also been suggested as being partly responsible for the haemostatic failure in uraemia. In this thesis an attempt has been made to define the defect in platelet function in uraemia, to assess the effect of haemodialysis on the defect and to demonstrate by in vitro tests the effect on the reactivity of platelets to adenosine diphosphate of certain substances known to be present in increased amounts in uraemic plasma. The discovery of platelets, their morphology and the role they play in haemostasis and thrombosis is described. An historical account is given of the progress of knowledge on the bleeding tendency in uraemia and the evolution of ideas on aetiology and methods used in these studies. An account is given on the materials and methods used to study some of the properties of platelets in normal controls and uraemic patients. These include a method for estimation of platelet aggregation by addition of calcium and calcium plus adenosine diphosphate (ADP) in an artificial circulation system (the Chandler tube technique), and by a turbidimetric method. Platelet aggregation with ADP and its reversal was studied by a turbidimetric system. The ability of platelets to adhere to glass surfaces was measured by a modified Hellem's glass bead column method. Platelet factor 3 availability was estimated by determining the 'Stypven' time of kaolin activated platelet-rich plasma (the method of Spaet and Cintron). A brief outline of the basis of each method and a discussion of some of the possible sources of error in the basic techniques are given with each method. Experiments on the effect of factors influencing the results of some of the tests were also described. The addition of ADP to platelet-rich plasma in the Chandler tube system resulted in significant shortening of the platelet aggregation time. When calcium and calcium plus ADP were added to platelet-rich plasma in turbidimetric system, a significant positive correlation was obtained between the platelet-rich plasma platelet count and the platelet aggregation time, duration of platelet aggregation and the fall in optical density occurring just before clot formation. A similar correlation was found with the clotting time and the platelet count. The addition of ADP as well as calcium significantly prolonged the duration of platelet aggregation occurring just before clot formation. When the results from normal controls and uraemic patients were compared, no difference was obtained in the mean aggregation time and clotting time, although uraemic patients had a significantly lower platelet count. However, the duration of platelet aggregation occurring before clot formation in the calcium plus ADP experiment v/as found to be prolonged in most of the uraemic patients examined. This may be a reflection of a qualitative platelet defect in uraemia resulting in inability of the platelets to release a normal amount of ADP in response to thrombin. ADP-induced platelet aggregation in normal control and uraemic patients was also investigated by the turbidimetric system. In normal controls a positive correlation was found between platelet disaggregation and the platelet count, but not between the count and platelet aggregation. However, when the results of experiments in which the platelet count was diluted with platelet-poor plasma were included, both aggregation and disaggregation were significantly correlated with the platelet count. A positive correlation also existed between platelet aggregation and disaggregation. Because of these correlations with the platelet count, the results from normal subjects and uraemic patients were grouped into four ranges of platelet count and the mean values compared. Platelet aggregation and disaggregation in uraemic patients were significantly lower than in normal controls. (Abstract shortened by ProQuest.)