Dilute blood clot lysis time and electrophoretic lipoprotein fractions in a population sample of healthy Romanians.

Serum total lipids and cholesterol, electrophoretically determined lipoprotein concentrations, serum pseudocholinesterase and dilute blood clot lysis time were determined in 630 healthy subjects (287 men and 343 women) aged 20-60, working in the food industry. A high incidence of over-weight was noted ranging from 22.4% in women aged 20-40 to 58.7% in men aged 41-60. Over-weight subjects presenting higher levels of serum cholesterol, total lipids and of the pre-beta electrophoretic fraction also had a higher pseudo-cholinesterase activity and a more delayed clot lysis time than normal-weight subjects matched as to age and sex. When the material was divided into quintiles for pre-beta- and beta-lipoproteins, a highly significant delay of fibrinolysis was noted in the fourth and fifth quintiles for pre-beta-lipoproteins, but no significant changes of lysis time occurred with increasing concentrations of beta-lipoproteins. Possible explanations of the abovementioned findings are briefly discussed.

Increased ristocetin-cofactor in acute myocardial infarction: a component of the acute phase reaction.

When compared to the values obtained in healthy normal-weight, normolipemic controls, the plasma level of ristocetin-cofactor (VIII:R-cof.) was found to be much higher in patients with acute myocardial infarction and in postoperative conditions (4--5 days after a major surgical intervention). A lesser increase of VIII:R-cof. was noted in atherosclerotic patients without acute occlusive accidents and no significant changes of this plasma factor could be observed in hyperlipemic subjects without obvious clinical atherosclerosis. Serial studies emphasized a tendency towards normalization of plasma VIII:R-cof. as the acute phenomena of a myocardial infarction subsided. The above mentioned data suggest that the high levels of VIII:R-cof. recorded in myocardial infarction are mainly caused by a systemic acute phase reaction and to a lesser extent by endothelial damage. Delayed clearance of VIII:R-cof. subsequent to a hepatic dysfunction or to a modified pattern of protein metabolism during the above mentioned acute phase reaction might also contribute to the high level of this plasma factor.

Plasma factor XIII and platelet factor XIII in hyperlipaemia.

Plasma factor XIII activity measured by a quantitative assay was found to be significantly higher in hypertriglyceridaemic patients (type IV and combined hyperlipoproteinaemia), as compared to normolipaemic controls. No such elevation in plasma factor XIII activity was found in patients with type Ha hyperlipaemia. Plasma pseudocholinesterase was found to parallel the elevated factor XIII activity in hypertriglyceridaemic subjects. In contrast, platelet factor XIII activity was not raised in hyperlipaemic subjects, and plasma factor XIII was found to be normal in a normolipaemic subjects with thrombocythaemia. It was concluded that there is no significant contribution from platelets to plasma factor XIII activity, and that the observed increase in plasma factor XIII in hypertriglyceridaemia results from enhanced hepatic synthesis of the enzyme.

Tissue-type plasminogen activator (t-PA) and dilute blood clot lysis time in nephrotic patients.

When compared to normal weight normolipidemic control subjects, dilute blood clot lysis time was found to be obviously (p less than 0.001) prolonged in hypertriglyceridemic patients without proteinuria and slightly (p less than 0.05) accelerated in hyperlipidemic nephrotic patients in spite of their very high levels of plasma fibrinogen. As a result the ratio plasma fibrinogen (mg/dl) per clot lysis time (minutes) was 1.241 +/- 0.08 (X +/- SEM) in control subjects, 0.574 +/- 0.07 in hypertriglyceridemic patients and 2.69 +/- 0.172 in nephrotic patients. This finding suggesting that a larger amount of fibrin is rather readily dispersed from dilute blood clots of nephrotic patients was associated with higher levels of plasma t-PA:Ag (9.45 ng/ml +/- 1.18 in nephrotic patients versus 5.8 ng/ml +/- 1.23 in controls before venous occlusion and respectively 33.1 ng/ml +/- 3.83 versus 20.3 +/- 3.40 in controls after venous occlusion). Plasminogen activator activity of the euglobulins as assessed by the bovine fibrin-agarose plate was significantly higher in nephrotic patients only after venous occlusion. Plasma samples of nephrotic patients exerted a more potent inhibition of fibrinolysis in a urokinase activated system. This effect was, however, mainly due to the high levels of alpha 2 macroglobulin in nephrotic plasma which apparently have little influence on dilute blood clot lysis time.

Comparative behaviour of the components of the factor VIII complex in acute myocardial infarction.

The three components of the factor VIII complex: VIII coagulant (VIII:C), VIII related antigen (VIII R:Ag) and the VIII related von Willebrand factor (VIII R:WF) were studied in patients with acute myocardial infarction (AMI). Using a carefully standardized technique for the determination of VIII R:WF, a significantly higher R:WF level was found in 32 patients compared to 19 control subjects, confirming our previous results. However VIII R:AG was increased to an even greater extent, resulting in a VIII R:Ag/VIII R:WF ratio of 1.58 +/- 0.084 in patients, compared to 1.21 +/- 0.045 in controls. A similar increase of the VIII R:AG/VIII:C ratio was noted in the 13 patients in whom VIII:C was investigated. In 7 patients with severe AMI who could be investigated twice the plasma levels of both VIII R:Ag and VIII R:WF were found to be lower a week after the acute event than during the first 48 hours. However the VIII R:Ag/VIII R:WF ratio was not significantly reduced after 7 days. Acute phase reaction and endothelial injury resulting in release of multimers which are less polymerised are probably involved in the above changes.

Increased plasma antithrombin III level in hyperlipidemic subjects.

When compared to values obtained in healthy normolipidemic normal weight control subjects, the plasma antithrombin III level determined by immunological, clotting and thrombin-agarose diffusion techniques was found to be obviously decreased in patients with decompensated cirrhosis of the liver and slightly but significantly increased in hyperlipidemic and especially in hypertriglyceridemic subjects. Plasma antithrombin III was positively correlated with serum cholesterol level, the logarithm of serum triglyceride concentration and serum pseudocholinesterase activity. A weaker correlation between plasma fibrinogen and antithrombin III was noted in the investigated clinical material. It is suggested that the accelerated fatty acid and lipoprotein turnover occurring in many subjects with type IIb and type IV hyperlipoproteinemia might be accompanied by an enhanced hepatic protein synthesis involving various liver secretion enzymes and clotting factors as well as antithrombin III.

Increased level of the complement C3 protein in endogenous hypertriglyceridemia.

When compared to values obtained in normalweight, normolipidemic control subjects, the level of complement C3 protein and total complement activity (CH50) were found to be obviously decreased in patients with decompensated cirrhosis of the liver and slightly but significantly increased in subjects with type IIb and type IV hyperlipoproteinemia. C3 protein level was positively correlated with the concentration of serum cholesterol, the logarithm of serum triglyceride concentration, serum pseudocholinesterase and total complement activity. There were no significant differences concerning C3 protein level between hyperlipidemic subjects with clinical atherosclerosis and those without documented vascular disease. It is suggested that accelerated lipoprotein turnover occurring in many subjects with type IIb and type IV hyperlipoproteinemia might enhance the synthesis of several liver produced plasma enzymes and proteins including the C3 protein of the complement system.

Transient elevation of serum bile acids during acute pancreatitis.

An increase of serum bile acids was detected in patients with biliary acute pancreatitis who could be investigated during the first 24 hours after the onset of the acute phenomena. Serum bile acids levels, as well as alpha-amylase activity, however rapidly decreased and were found within normal limits after 48-72 h, while the increased serum gamma-glutamyltransferase activity persisted for at least 7 days. Changes affecting serum bile acids in patients with acute pancreatitis unassociated to biliary disease or in patients with acute biliary disease unaccompanied by a pancreatic reaction were less important. Mechanisms leading to these changes and their possible pathogenic relevance are briefly discussed.

Increased values of antipyrine clearance in type IV hyperlipoproteinemia.

When compared to values obtained in 17 normal weight normolipidemic control subjects (41.63 +/- 2.73 ml X min-1) antipyrine clearance determined in the saliva was found to be obviously decreased in the 10 patients with liver cirrhosis (21.88 +/- 0.79) and significantly increased in the 17 subjects with type IV hyperlipoproteinemia (59.91 +/- 4.59). Antipyrine clearance was positively correlated with both serum triglyceride concentration (r = 0.574; p less than 0.001) and serum cholinesterase activity (r = 0.705; p less than 0.001) and these correlations persisted even after the exclusion of cirrhotic patients. It is suggested that the accelerated hepatic secretion of very low density lipoproteins and of many export proteins and enzymes noted in most hypertriglyceridemic subjects is accompanied by an enhanced activity of liver microsomal enzymes involved in drug metabolism.

Platelet aggregation is inhibited by long chain acyl-CoA.

Oleoyl coenzyme A and other acyl-CoA derivatives inhibited ADP or thrombin-induced aggregation of platelets. Arachidonic acid-induced aggregation was also inhibited, but not the slower aggregation caused by 1-oleoyl-2-acetylglycerol or tetradecanoyl-phorbol-13-acetate. Coenzyme A and free fatty acids had little or no effect, and transfer of labeled oleate from oleoyl Co-A to other lipid classes was not detected. Because acyl Co-A compounds have recently been shown to modulate protein kinase C activity, acyl Co-A may provide a useful tool for investigating activation sequences in platelets and other membranes.

Inhibition and potentiation of platelet function by lysolecithin.

The effects of lysolecithin (LPC) on aggregation, serotonin release, shape, and lysis of rabbit, pig, or human platelets in platelet-rich plasma (PRP) or Tyrode albumin solution were examined during prolonged incubation. LPC added to citrated or heparinized PRP from humans or rabbits at a final concentration above 100 muM caused instantaneous inhibition of platelet aggregation induced by adenosine diphosphate (ADP), epinephrine (human PRP only), collagen, or thrombin. The inhibitory effect of LPC was found to be partially reversible over a period of 60-90 min. LPC at final concentrations above 30 muM also caused inhibition of ADP-, collagen-, and thrombin-induced aggregation and collagen- and thrombin-induced release of serotonin in suspensions of rabbit, pig, or human platelets. With washed platelets, the inhibitory effect not only rapidly disappeared but was followed by transient potentiation of aggregation and serotonin release. This potentiating effect of LPC was most pronounced when thrombin was used as stimulus. Both inhibition and potentiation were observed at concentrations of LPC that did not cause a significant change in platelet shape or loss from platelets of lactic dehydrogenase. Inhibition and potentiation were also observed when platelets were added to suspending medium containing LPC, although considerably higher concentrations of LPC were required under these conditions. Potentiation was not observed when LPC was added to citrated or heparinized rabbit or human PRP or to washed rabbit platelets suspended in a medium containing 4% bovine serum albumin. It seemed likely that some or all of the observed effects of LPC on platelet function were due to structural modification of the platelet membrane insufficient to result in gross membrane damage or platelet lysis. In addition, the results of experiments using 14C-LPC seemed to indicate that the observed potentiating effect of LPC on platelet function may be related to its rapid uptake and metabolism by the platelets.