In Vitro Effect of p-Chlormercuribenzoate upon Dilute Blood Clot Lysis Time in Hyperlipemia

Abstract

SummaryIn comparison to values obtained in normal-weight normolipenic controls, dilute blood clot lysis time was found to be prolonged in resting and exercised patients with endogenous hypertriglyceridemia. Lysis time was also prolonged in overweight subjects with only slightly increased serum lipids but it was not significantly changed in type II-a hyperlipoproteinemia. An obvious acceleration of clot lysis was noted in patients with decompensated cirrhosis of the liver. Inclusion of p-chlormercuribenzoate (PCMB) into the diluted blood clot caused an acceleration of lysis time. This effect was particularly obvious with hypertriglyceridemic blood and minimal with blood obtained from cirrhotic patients. Addition of various amounts of heat-defibrinated plasma to blood from cirrhotic patients caused a proportional prolongation of clot lysis time and this effect was greatly diminished in the presence of PCMB. Similar amounts of serum had a much lesser effect than defibrinated plasma. Inhibition of fibrin cross-linking by PCMB was confirmed by sodium dodecylsulfate polyacrylamide gel electrophoresis.The present data complete previous observations concerning a higher plasma factor XIII activity in type II-b and type IV hyperlipoproteinemia and suggest that an increased crosslinking of fibrin might partially explain the deficient thrombolysis of hypertriglyceridemic patients.

Impact of Mild hypertriglyceridemia on fibrinolysis, Lp(a), and platelet activation indexes in mildly hypercholesterolemic patients

“…The im- portance of these results lies in the fact that PAl-1 is considered to be an additional risk factor for the atherosclerotic and thrombotic process [12,14,34] by inhibiting the fibrinolytic mechanism and reducing the removal of fibrin deposits [35]. Many studies have shown the presence of high plasma concentrations of PAI-1 in CHD patients [20][21][22][23][24][25][26][27]. More recently, Mussoni et al [36] studied the capacity of atherogenic lipoproteins, in particular VLDLs, to release PAI-I from the endothelial cells of the umbilical vein in vitro.…”

“…Furthermore, the studies published in literature up to now were carried out mostly on markedly hypertriglyceridemic patients [9,[22][23][24][25] and on patients with CHD with or without other risk factors for atherosclerosis associated with decreased fibrinolytic activity (hypertension, diabetes, and obesity) [ 18,26,27], and were therefore unable to shed light on the effect of mild hypertriglyceridemia on fibrinolysis and platelet activity.…”

Factor XIII and Fibrinolytic Resistance

“…This concept is supported by my observations, which began 26 years ago and emphasize increased plasma factor XIII levels in hypertriglyceridemic patients 2-4 who also display high plasma fibronectin concentrations 4 and an obviously prolonged dilute blood clot lysis time. 5 Because the in vitro inhibition of factor XIII by p-chloromercuribenzoate led to an acceleration of clot lysis, 5 I presumed that the association of high plasma factor XIII levels with impaired fibrinolysis was not merely casual. My colleagues and I also showed that platelet factor XIII is unlikely to make any significant contribution to plasma factor XIII levels.…”

α2-Antiplasmin, Plasminogen Activator Inhibitor (PAI) and Dilute Blood Clot Lysis Time in Selected Disease States

“…Dilute blood clot lysis time (DBCLT) was assessed acording to Gallimore et al (22) as previously described (11) in the presence and in absence of 50 11M p-chlormercuribenzoate (PCMB) a potent inhibitor of factor XIII. Preliminary investigations emphasized that PCMB 50 11M exerts only a minor effect on PAl activity (a 10-15% reduction) as determined by the COATEST-PAI procedure.…”

“…For example plasma PAl levels are increased not only in atheroscle~otic hyperlipidemic patients (10) who also display a retarded dilute blood clot lysis (11) but also in many cases with severe hepatic cirrhosis (12,13) in whom clot lysis was found to be accelerated (11) probably in relation to their reduced plasma levels of u2AP (14) and factor XIII (15). On the other hand in spite of the high plasma levels of fibrinogen and factor XIII the dilute blood clot lysis was not retarded but rather accelerat;d in patients with the nephrotic syndrome (15,16).…”