Clinical studies of beta-thromboglobulin
Smith, Robert C.
Beta-thromboglobulin is a platelet specific protein of molecular weight 35,000, stored in the alpha granules and released during aggregation. Its precise function is unknown but it may act as a 'packing protein' in the alpha granules. Radioimmuno¬ assays to measure it in plasma and urine have been developed. Meticulous techniques of processing and sampling are necessary to prevent artefactual release. In healthy subjects the upper limit of the normal range is 80 ng/ml in plasma and 0.21 ng/ml in urine. If the (3TG concentration of the plasma is artificially elevated it is cleared exponentially with a plasma half life of about 80 mins. Only a tiny proportion of the infused dose appears in the urine. Many drugs are known to affect platelet function but Aspirin, although it has a potent anti-aggregatory action, has no effect on the plasma 3TG concentration. Heparin, however, may produce raised plasma $TG concentrations some hours after injection. Only 65% of patients with venous thromboembolism had elevated $TG concentrations on the day of presentation. The degree of rise in concentration was related to the presence of pulmonary embolism but not to the duration of symptoms or the extent of the thrombus. However, 85% of patients with venous thromboembolism had elevated urinary $TG concentrations and so the urinary 0TG concentration is a more valuable diagnostic test of venous thromboembolism than the plasma concentration. Operation had a considerable effect on plasma STG concentration which was most marked in patients undergoing vascular surgery. Many factors affected the plasma concentrations following operation but major infections produce the greatest rise. A small, but statistically insignificant rise occurred at the time of development 125 of deep vein thrombosis diagnosed by the I fibrinogen uptake test. The other factors affecting the plasma STG concentration in the post operative period grossly limited its value in the diagnosis of post operative deep vein thrombosis. It was likewise of little value in the identification of graft thrombosis in those undergoing arterial reconstructions. The urinary STG assay had similar disadvantages to the plasma assay in the post operative period. The study on patients with atherosclerosis revealed that many had elevated plasma concentrations regardless of the clinical extent of the disease but most patients had normal urine concentrations. The assessments of plasma and urinary STG concentrations are a sensitive measure of platelet activity in experimental situations but the many factors which affect them and the relatively short plasma half life severely limit their clinical use.