Incorporation of Fibrin, Platelets, and Red Blood Cells into a Coronary Thrombus in
Time and Space
The formation of arterial thrombi is the key event leading to myocardial infarction
(MI) and ischemic stroke. In vitro and in vivo animal studies have been fundamental
to our mechanistic understanding of thrombosis and yielded a range of antiplatelet,
anticoagulant, and thrombolytic therapies that remain the cornerstone of cardiovascular
treatment today, albeit with an inherent bleeding risk.[1] With the recent adoption of high-resolution imaging techniques and thrombus-extraction
technologies, the architecture/composition of human thrombi has come into sharp focus.[2]
[3]
In this edition of Thrombosis and Haemostasis, Maly and colleagues[1] use scanning electron microscopy to analyze the composition of thrombi aspirated
from 34 patients with ST-elevation MI. Thrombi from “early presenters” (<2 hours)
exhibited a homogenous structure and were rich in platelets with less fibrin and red
blood cells (RBCs). In contrast, thrombi from “late presenters” (>12 hours) were predominantly
composed of RBCs, with significantly less platelets and fibrin. Moreover, thrombi
displayed a heterogeneous architecture, with platelet-rich areas at the seeding portion
of the thrombus in contrast to the propagating (often proximal) portion that was composed
almost entirely of RBCs. It is noteworthy that the RBCs contained within the core
of late thrombi had a dense-packed, polyhedral morphology and thicker fibrin stands.
These detailed analyses from Maly et al and others afford important clinical implications.
First, the structure of older thrombi helps explain why these thrombi are more resistant
to fibrinolysis and the potential benefit of mechanical thrombus extraction. Second,
the architecture of pathological thrombi appears to be distinct to “hemostatic clots,”[3] raising the prospect that important differences in the processes that govern thrombosis
and hemostasis can potentially be exploited therapeutically. Third, these findings
highlight the potential benefits of targeting thrombolytics to components of thrombi,
such as platelets, fibrin, and RBCs, and suggest that employing specific reperfusion
strategies according to thrombus composition may provide clinical benefit.
