Composition of coronary thrombus in acute myocardial infarction

Abstract

Objectives: We sought to analyze the composition of coronary thrombus in vivo in ST-segment elevation myocardial infarction (STEMI) patients.

Background: The dynamic process of intracoronary thrombus formation in STEMI patients is poorly understood.

Methods: Intracoronary thrombi (n = 45) were obtained by thromboaspiration in 288 consecutive STEMI patients presenting for primary percutaneous intervention, and analyzed using high-definition pictures taken with a scanning electron microscope. Plasma biomarkers (TnI, CRPus, IL-6, PAI-1, sCD40 ligand, and TNF-α) and plasma fibrin clot viscoelastic properties were measured simultaneously on peripheral blood.

Results: Thrombi were mainly composed of fibrin (55.9 ± 18%) with platelets (16.8 ± 18%), erythrocytes (11.5 ± 9%), cholesterol crystals (5.2 ± 8.4%), and leukocytes (1.3 ± 2.0%). The median ischemic time was 175 min (interquartile range: 140 to 297). Ischemic time impacted thrombi composition, resulting in a positive correlation with intracoronary thrombus fibrin content, r = 0.38, p = 0.01, and a negative correlation with platelet content, r = -0.34, p = 0.02. Thus, fibrin content increased with ischemic time, ranging from 48.4 ± 21% (<3 h) up to 66.9 ± 9% (>6 h) (p = 0.02), whereas platelet content decreased from 24.9 ± 23% (<3 h) to 9.1 ± 6% (>6 h) (p = 0.07). Soluble CD40 ligand was positively correlated to platelet content in the thrombus (r = 0.40, p = 0.02) and negatively correlated with fibrin content (r = -0.36; p = 0.04). Multivariate analysis indicated that ischemic time was the only predictor of thrombus composition, with a 2-fold increase of fibrin content per ischemic hour (adjusted odds ratio: 2.00 [95% confidence interval: 1.03 to 3.7]; p = 0.01).

Conclusions: In acute STEMI, platelet and fibrin contents of the occlusive thrombus are highly dependent on ischemia time, which may have a direct impact on the efficacy of drugs or devices used for coronary reperfusion.

Figure 1

Analysis of clot surface with 10+ (or more) areas to average the thrombus heterogeneity (above) and perform semi quantitative analysis (below).

Figure 2. Scanning electron micrograph at 3000x magnification

This portion is mainly composed of erythrocytes (b) trapped in a fibrin mesh (c) with few platelet aggregates (d) and rare white cells (a)

Figure 2 bis. Scanning electron micrograph at 3000x magnification

This portion is mainly composed of platelet aggregates with a few cholesterol crystals (in yellow)

Figure 3

Flow chart of the study.

Figure 4. Thrombi composition in n=44 STEMI patients (early presenters)

Red lines indicate median and IQR [25%-75%].

Figure 5. Impact of time on thrombus composition

P-values are given for comparison with the group < 3 hours as a reference with multiple student t -test. * p value <0.05. Multiple comparison was done with the Dunnett's test resulting in a p value = 0.044 for fibrin and non significant for platelet content

Figure 6. Evolution of the percent thrombus composition for each component in % (Y axis) relative to ischemic time (min) (X axis)

Lines represent linear regression for correlation with ischemic time.

Figure 7. Results of fibrin clot viscoelastic properties and response to fibrinolysis according to ischemic time

No significant differences were found between groups with the Dunnett's test.