Summary.We studied tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) in healthy individuals divided by smoking habit into current smokers, former smokers and non-smokers (who had never smoked). Plasma PAI-1 antigen was significantly higher in smokers than in non-smokers with intermediate levels in former smokers. A similar trend was observed for plasma PAI activity but this did not reach statistical significance. Platelet PAI-1 and plasma t-PA were not significantly different when comparing the three groups. After venous occlusion t-PA rose significantly in all groups; no significant change in plasma PAI-1 was observed. The ratio of t-PA to PAI-1 in plasma was similar in non-smokers and former smokers but lower in smokers, suggesting that there is at least partial restoration of plasma fibrinolytic potential after smoking cessation. Plasma PAI-1 antigen and PAI activity correlated with estimated pack-years of cigarettes smoked among smokers and former smokers. When all subjects were studied collectively, plasma PAI-1 correlated strongly with plasma t-PA and triglycerides; plasma t-PA also correlated strongly with triglycerdes.We conclude that chronic smoking is associated with impaired fibrinolysis in plasma and that this largely reflects elevated plasma PAI-1 in smokers. Smoking does not appear to affect the response to venous occlusion. The postulated effect of chronic smoking on plasma PAI-1 may be mediated by the influence of smoking on triglycerides and insulin resistance. Stopping smoking appears to return impaired fibrinolysis towards normal. Smoking does not quantitatively affect the platelet pool of PAI-1. Smoking habit should be controlled for in clinical analyses of PAI-1 and t-PA.

SUMMARY Serum cx2-macroglobulin levels have been determined in diabetic patients by quantitative radial immunodiffusion and compared with those observed in age-and sex-matched controls. In addition, the results in diabetics have been analysed with respect to such variables as the age and sex of the patient, the duration of disease, treatment, control, and the occurrence of retinopathy or nephropathy.The (x2-macroglobulin levels in diabetic patients were found to be significantly higher than in ageand sex-matched controls, thus confirming previous observations. However, these differences were most apparent in the more extreme age groups. Multiple regression analysis also revealed that the only variables contributing significantly to the regression apart from age and sex were control and retinopathy.

SUMMARY Plasma ,8-thromboglobulin, platelet factor 4, fibrinogen, fibrinopeptide A, antithrombin III, factor VIII related antigen, a2-macroglobulin, platelet count, and total glycosylated haemoglobin were measured in three well matched groups of subjects: non-diabetic controls, diabetics without retinopathy, and diabetics with proliferative retinopathy. /8-thromboglobulin and platelet factor 4 concentrations were significantly higher in the diabetics with retinopathy than in the controls and platelet factor 4 was also increased in the diabetics without retinopathy compared with controls. Fibrinogen concentration was raised in diabetics without retinopathy compared with controls, diabetics with retinopathy compared with controls, and diabetics with retinopathy compared with those without. Fibrinopeptide A concentration did not differ significantly between groups. Antithrombin III levels were increased in diabetics with retinopathy compared with controls, and in diabetics with retinopathy compared with those without. Factor VIII related antigen values were higher in both the diabetic groups when compared with the controls. Fibrinopeptide A concentration correlated with both /8-thromboglobulin and platelet factor 4 in each of the three groups.Haemostatic abnormalities in diabetes have been shown, although a hypercoagulable state has not been confirmed. These changes in platelet and coagulation function may be secondary to the development of microvascular disease and their role in the pathogenesis of retinopathy remains uncertain.Patients with diabetes mellitus have significantly increased morbidity and mortality as a consequence of specific microvascular disease, which results in conditions such as retinopathy and nephropathy. Although the precise cause of these vascular complications remains uncertain, evidence is accumulating that an imbalance of the haemostatic mechanisms may be entailed in their initiation or propagation.

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Serum alpha 2-macroglobulin (alpha 2m) and total glycosylated haemoglobin (HbA1) concentrations were measured in 110 insulin dependent Type 1 diabetics with minimal or no fundoscopic retinopathy, referred to as non-retinopaths, and in 52 proliferative retinopaths. Proteinuria was recorded in 8 (7%) non-retinopaths and 29 (56%) retinopaths and was accompanied by elevated alpha 2m concentrations in both groups of diabetics but only significantly so in the non-retinopaths. Diabetics without proteinuria showed a significant correlation between alpha 2m concentration and duration of diabetes, HbA1 and age (being higher at extremes of age). Alpha 2m concentrations were significantly higher in retinopaths than in non-retinopaths without proteinuria when allowance was made for the influence of age and duration of diabetes on alpha 2m. This difference may be attributed to the higher HbA, levels found in retinopaths than in non-retinopaths and was no longer evident when account was taken of the prevailing HbA1 concentration in individual patients.