Increased von Willebrand factor, P-selectin and fibrin content in occlusive thrombus resistant to lytic therapy

Abstract

Therapeutic fibrinolysis is ineffective in 40 % of ST-segment elevation acute myocardial infarction (STEMI) patients, but understanding of the mechanisms is incomplete. It was our aim to compare the composition of coronary thrombus in lysis-resistant STEMI patients with that of lysis-sensitive patients. Intracoronary thrombi (n=64) were obtained by aspiration in consecutive STEMI patients. Of them, 20 had received fibrinolysis and underwent rescue percutaneous coronary intervention (r-PCI, lysis-resistant patients) and 44 underwent primary PCI (p-PCI). Lysis-sensitivity was determined in vitro by clot permeability measurements and turbidimetric lysis in plasma of 44 patients undergoing p-PCI and 20 healthy donors. Clot-lysis sensitivity was defined as a clot-lysis time not greater than 1 SD over the mean of healthy donors. Coronary thrombus composition in 20 lysis-resistant and in 20 lysis-sensitive patients was analysed by immunofluorescence with confocal microscopy. Plasma biomarkers (P-selectin, VWF, PAI-1, t-PA, D-dimer, TF pathway markers, plasmin and CD34+) were measured simultaneously on peripheral blood. Lysis-resistant clots had higher levels of fibrin (p=0.02), P-selectin (p=0.03) and VWF (p=0.01) than lysis-sensitive clots. Among thrombi obtained ≤ 6 hours after onset of symptoms, those from lysis-resistant patients showed a higher content in fibrin than those from p-PCI patients (p=0.01). Plasma PAI-1 (p=0.02) and D-dimer levels were significantly higher (p=0.003) in lysis-resistant patients, whereas plasmin levels were lower (p=0.03). Multivariate analysis showed the content of fibrin and VWF within thrombus as predictors of thrombolysis resistance. In conclusion, coronary thrombi in STEMI patients resistant to fibrinolysis are characterised by higher fibrin, P-selectin and VWF content than lysis-sensitive thrombi.

Microfluidics contrasted to thrombelastography: perplexities in defining hypercoagulability

“…Prior studies on fibrin formation and clot resistance have demonstrated that slow growing clots with multiple side branches are fibrinolytic resistant. 29,30 This was supported by our data in which TEG angle (a measurement of fibrinogen function) was inversely related to OSp in the AR chip in the presence of t-PA, whereas LY30 unexpectedly inversely correlated with OT. As the PL chip neglects any contribution of fibrinogen to clot, these patients potentially could have had an adaptive response to downregulate their platelets from increased fibrinogen function.…”

Plasminogen activator inhibitor-1 activity and long-term outcome in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention: a prospective cohort study

“…The major drawback of this study were the inadequate financial resources, which limited the sample size. However, the number of the included patients was not much smaller than in other PAI-1 studies in acute coronary syndromes ( 7 , 17 , 29 , 30 ). Post-hoc power analysis showed that χ 2 and Mann-Whitney U tests for determining the difference in PAI-1 activities between dead and alive patients at 5-year follow-up had adequate power (1.000 for both tests at 5% significance level, G*Power 3.1.9.3, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany) ( 31 ).…”

“…Higher plasma PAI-1 concentrations were detected in acute STEMI patients with fibrinolysis-resistant thrombi ( 17 ), while higher PAI-1 rise was detected in patients treated with streptokinase and persistent coronary artery occlusion ( 18 ). This indicates that PAI-1 rise influences the outcome similarly regardless of the reperfusion strategy.…”

The Effects of Curcumae Longae Radix, Curcuma phaeocaulis Radix and Their Processed Products on Epo/EpoR Pathway and CD62p

“…When the platelets are stimulated, it is rapidly expressed on the surface of the platelet membrane, which mediates the adhesion of platelets and vascular endothelium to the inflammatory cells and the adhesion of platelets, and promotes fibrin deposition and thrombosis to form ( Qi and Wang, 2014 ). CD62p is currently one of the most specific indicators that can reflect platelet activation ( Bonacina et al, 2016 ; Sambola et al, 2016 ). The results showed that, compared with CG, the expression of CD62p in the MG increased significantly, indicating that the platelet activation was enhanced, which was consistent with the blood stasis syndrome.…”