A deficiency of free protein S, known to increase the risk of peripheral venous thrombosis, has not been well described in patients with cerebrovascular disease. In a pilot study of 35 patients with symptomatic cerebrovascular disease, using a qualitative crossed immunoelectrophoresis assay we found eight patients with a free protein S deficiency. A Laurell immunoelectrophoresis assay was used to quantify the percentage of free protein S after removal of the inactive protein S C4b-binding protein complex by precipitation with polyethylene glycol 8000. In a quantitative study of 103 patients with cerebrovascular disease, 21 had a free protein S that was <20% of the average normal total protein S concentration (normal range 20-40%); 19 had suffered cerebral infarction and the other two had suffered intracranial hemorrhage. The frequency of free protein S deficiency in this group of stroke patients was far higher than the expected prevalence in the general population. (Stroke 1989;20:1657-1661
We have determined the extent of fragment X formation during thrombolytic therapy by integration over time of the plasma fibrinopeptide B#1-42 concentration. This peptide is quantitatively released when fragment X is formed by plasmin action on fibrinogen or fibrin I. In response to streptokinase (SK) and rt-PA, 264±54 and 95±12 mg/dl respectively of fibrinogen was converted to fragment X. By immunoblotting, fragment X was demonstrated as early as 5 min after SK and 30 min after rt-PA, and was still evident 24 h after treatment. Patients treated with SK showed extensive further plasmin degradation of fragment X to fragments Y and D. Thus fragment X concentrations tend to be more similar in the two groups than would be expected from the extent of fibrinogen breakdown. Fragment X forms clots, but these have lower tensile strength and are more susceptible to further plasmin lysis than clots of fibrin. Thus the similar bleeding observed in the two treatment groups might be a reflection of their similar plasma fragment X concentrations.
Pathologic and experimental evidence indicates that platelet activation and fibrin formation contribute to the pathogenesis of angina pectoris, coronary vasospasm and myocardial infarction. Detection of localized intravascular platelet activation and fibrin formation in vivo by selective blood sampling requires catheters that do not induce coagulation ex vivo. We studied the effect of heparin bonding of catheter surfaces on activation of the coagulation system by cardiovascular catheters. Woven Dacron, polyvinylchloride, and polyurethane catheters were tested and compared with identical catheters with heparin-bonded surfaces in 47 patients undergoing percutaneous cardiac catheterization. Platelet activation was measured by radioimmunoassay of plasma platelet factor 4 (PF4), /3-thromboglobulin (BTG), and thromboxane B2 (TXB2) in blood samples withdrawn through catheters, and fibrin formation was assessed by determination of fibrinopeptide A (FPA) levels. In blood samples collected through conventional catheters, FPA, PF4, BTG, and TXB2 levels were markedly elevated; blood sampling through heparin-bonded catheters had no significant effect on FPA, PF4, BTG, or TXB2 levels. Scanning electron microscopy disclosed extensive platelet aggregates and fibrin strands adherent to the surface of conventional catheters but not to heparin-bonded catheter surfaces. This study demonstrates that (1) collection of blood samples through cardiovascular catheters causes artifactual elevation of FPA, PF4, BTG, and TXB2 levels, and (2) heparin-bonded catheter surfaces effectively prevent catheter-induced platelet a-granule release and fibrin formation on catheter surfaces. Heparin-bonded catheters will facilitate investigation of the role of intravascular coagulation in coronary artery disease by eliminating catheter-induced fibrin formation and platelet activation. Circulation 70, No. 5, 843-850, 1984. RECENT clinical and experimental evidence suggests that platelet activation and fibrin formation in vivo may be fundamentally important in clinical complications of atherosclerotic coronary artery disease, including unstable angina,1 myocardial infarction,24 and sudden death.5 Investigation of platelet release and fibrin formation in vivo has been facilitated by the recent development of radioimmunoassays for specific proteins and prostanoids released by activated platelets6'7 and peptides released during fibrin formation.8Platelet factor 4 (PF4) and ,3-thromboglobulin (BTG) are platelet-specific proteins secreted from platelet agranules during the platelet-release reaction.9 10
Coagulation system activity in vivo is a well-recognized consequence of advanced atherosclerotic disease, the association of coagulation system activity with atherogenesis is much less clear. The data reviewed here argue against ongoing increased coagulation system activity in persons with hyperlipidemia. The possibility remains that episodic activity could easily be missed with available tests, such bursts of activity might well require new agents and strategies for effective control. Failure to find evidence of increased coagulation activity in patients with hyperlipidemia does not refute models of atherogenesis based on thrombosis. Rather, the data reviewed here should cause us to focus attention on the time scale of such events. On the other hand, the findings do allow for a simpler interpretation of data showing evidence of activation of coagulation in patients with concurrent hyperlipidemia.
We have determined the plasma level of fibrinopeptide A as a specific index of thrombin activity during the infusion of a thrombolytic agent in patients with acute myocardial infarction. Peripheral venous plasma levels of fibrinopeptide A increased following the initiation of thrombolytic therapy from 2.7 nmol/L to a peak of 13.0 nmol/L at 30 minutes with streptokinase and from 1.1 nmol/L to a peak of 10.7 nmol/L at 90 minutes with tissue plasminogen activator. The amount of fibrinogen converted to fibrin I was determined by integration of the plasma level of fibrinopeptide A over time. The amount of fibrin I formed over the five-hour period from the start of drug infusion was approximately 10 mg/dL in response to either streptokinase or recombinant tissue plasminogen activator. We conclude that activation of coagulation occurs in response to thrombolytic therapy despite heparin administration. This thrombin action, though transient, would be sufficient to cause rethrombosis if localized and incompletely opposed by fibrinolytic activity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.