Studies on a complex mechanism for the activation of plasminogen by kaolin and by chloroform: the participation of Hageman factor and additional cofactors.

As demonstrated by others, fibrinolytic activity was generated in diluted, acidified normal plasma exposed to kaolin, a process requiring Hageman factor (Factor XII). Generation was impaired by adsorbing plasma with glass or similar agents under conditions which did not deplete its content of Hageman factor or plasminogen. The defect could be repaired by addition of a noneuglobulin fraction of plasma or an agent or agents eluted from diatomaceous earth which had been exposed to normal plasma. The restorative agent, tentatively called Hageman factor-cofactor, was partially purified by chromatography and had an apparent molecular weight of approximately 165,000. It could be distinguished from plasma thromboplastin antecedent (Factor XI) and plasma kallikrein, other substrates of Hageman factor, and from the streptokinase-activated pro-activator of plasminogen. Evidence is presented that an additional component may be needed for the generation of fibrinolytic activity in mixtures containing Hageman factor, HF-cofactor, and plasminogen.The long-recognized generation of plasmin activity in chloroform-treated euglobulin fractions of plasma was found to be dependent upon the presence of Hageman factor. Whether chloroform activation of plasminogen requires Hageman factor-cofactor was not determined, but glass-adsorbed plasma, containing Hageman factor and plasminogen, did not generate appreciable fibrinolytic or caseinolytic activity. These studies emphasize the complex nature of the mechanisms which lead to the generation of plasmin in human plasma.

Plasma fibrinogen and plasminogen levels in health and in ischaemic heart disease.

Plasma fibrinogen and plasminogen levels were measured in 122 male and 56 female healthy adult subjects and in 64 men with ischaemic heart disease. Plasma fibrinogen levels were found to rise markedly and progressively with age in both male and female healthy subjects; plasminogen showed only a slight rise with age. No sex differences were found for either fibrinogen or plasminogen. The correlation between plasminogen and fibrinogen levels was low, reaching the 5% level of significance only in men. Patients with ischaemic heart disease were found to have significantly increased fibrinogen and plasminogen levels in the 31-45 years age group only.

Fibrinolysis in leukaemia.

Components of the blood fibrinolytic system were measured in 43 patients with leukaemia. Increased fibrinolytic activity, indicated by a reduced plasma plasminogen level, was found in 14 patients. The combination of severe thrombocytopenia and increased fibrinolysis appeared to be a determinant in the production of a haemorrhagic tendency in leukaemia.

The fibrinolytic enzyme system in hepatic cirrhosis and malignant metastases.

Components of the blood fibrinolytic system were measured in 18 patients with hepatic cirrhosis, in two patients with acute hepatic necrosis, and in 10 patients with hepatic metastases. The frequency of an elevation of plasminogen activator and a reduction in plasminogen in hepatic cirrhosis has been confirmed. Patients with compensated cirrhosis had low levels of the serum inhibitor of plasminogen activation while those with severe hepatic insufficiency or coma due to cirrhosis or hepatic necrosis had elevated levels. The presence of hepatic metastases was associated with reduced plasminogen activator levels and an increase in the fibrinogen concentration.

Studies on the fibrinolytic enzyme system in obesity.

Plasma fibrinolytic activity, inhibitors of fibrinolysis, and fibrinogen were estimated in 34 subjects of varying ratio of observed to standard weight. The inverse relationship between fibrinolytic activity and the ratio of observed to standard weight was confirmed. No significant correlation was found between anti-plasmin or anti-urokinase and the ratio of observed to standard weight. It was therefore concluded that the decreased plasma fibrinolytic activity in obese subjects is due to decreased production of plasminogen activator rather than to excessive inhibition.

Origin and employment of the medical graduates of the University of Aberdeen 1931-69.

A survey was made of the medical graduates of the University of Aberdeen, 1931-69. The recent increase of graduates of non-British origin, the continuing high intake of women and their subsequent attrition, and the high rate of emigration, have combined to reduce substantially the number of these graduates working in Britain.

The effect of prolonged exercise on the components of the blood fibrinolytic enzyme system.

1. The levels of the blood components of the fibrinolytic enzyme system were measured before, during and after a 4 hr period of exercise in eight subjects.2. Mean plasminogen activator level rose progressively over the first 3 hr with little further change during the 4th hr of exercise. Following the period of exercise there was a rise in a circulating anti-activator which was still present 20 hr after completion of the exercise.3. There was no alteration in the mean blood level of plasminogen, fibrinogen, anti-plasmin or a serum inhibitor of plasminogen activation during or following the exercise.4. The significance of the findings in relation to the mechanism of interaction of the components of the fibrinolytic system is discussed.