Co‐localization of von Willebrand factor with platelet thrombi, tissue factor and platelets with fibrin, and consistent presence of inflammatory cells in coronary thrombi obtained by an aspiration device from patients with acute myocardial infarction

Abstract

Summary. Background: Detailed histochemical analysis of coronary thrombi obtained freshly from acute phase of myocardial infarction patients may provide information necessary to understand the mechanism of coronary occlusive thrombus formation. Methods and Results: Coronary thrombi causing myocardial infarction were obtained from 10 consecutive patients of myocardial infarction in the acute phase, using a newly developed aspiration catheter. All the fixed specimens of coronary thrombi, by hematoxylin and eosin staining, were found to contain three major constituents, namely, platelets, densely packed fibrin and inflammatory cells, including polymorphonuclear and mononuclear cells, although their distribution in each specimen is totally heterogeneous. Immunohistochemical staining revealed the prominent presence of von Willebrand factor (VWF) at the sites of platelet accumulation, presence of tissue factor and platelets at the sites of deposition of fibrin fibrils. It also revealed the presence of CD16-, CD45-and CD34-positive cells, yet the functional roles of these cells have still to be elucidated. There are weak positive correlation between the number of inflammatory cells involved in the unit area of coronary thrombi specimen and the time of collection of the specimens after the onset of chest pain. Conclusions: In spite of various limitations, our results contain information suggesting the possible role of VWF in platelet-thrombus formation, possible important role played by tissue factor and activated platelets in the formation of fibrin fibrils, and the positive relationship between inflammatory cells migration and the formation of occlusive thrombi in human coronary arteries.

Association Between Circulating Level of CD40 Ligand and Angiographic Morphologic Features Indicating High-Burden Thrombus Formation in Patients With Acute Myocardial Infarction Undergoing Primary Coronary Intervention

“…Finally, the circulating level of sCD40L and the WBC count were independently predictive of HBTF in the IRA, whereas pre-PCI TIMI flow ≥1 was the only predictor of LBTF. Therefore, these findings further support the finding from a recent study 19 that inflammatory cells, including polymorphonuclear and mononuclear cells, and activated platelets are frequently obtained from human coronary thrombi following AMI.…”

Protective anti-inflammatory effect of ADAMTS13 on myocardial ischemia/reperfusion injury in mice

“…23 Moreover, VWF and ADAMTS13 were both identified in coronary thrombi isolated from patients with AMI, although UL-VWF has been detected in plasma from patients with AMI. 20,22,[24][25][26] Whereas it is difficult to directly compare the extent of acute injury in our experimental mouse model of AMI with the clinical risk of MI occurrence, these clinical data at least further indicate a role for ADAMTS13 in MI progression. One limitation of clinical case-control studies is the intricacy of determining whether low ADAMTS13 levels are cause or consequence of the cardiovascular event.…”

Von Willebrand Factor in Cardiovascular Disease

“…67,68 These studies have elegantly shown the colocalization of VWF with platelet thrombi, tissue factor, and platelets with fibrin in fresh coronary thrombi of patients with MI. Furthermore, shear-induced platelet aggregation and VWF binding to platelets is markedly enhanced in plasma from patients with AMI compared with control plasma.…”

“…66 Furthermore, detection of VWF in fresh, human coronary thrombi suggests a causative role of VWF in platelet thrombus growth. 67,68 The distinctive role of VWF is evidenced by elevated VWF levels and VWF activity in the context of ACS. The unweighted meanϮSD of published VWF data 64,69 -82 shows that patients with AMI (196Ϯ39%; nϭ877) have markedly increased VWF values compared with unstable angina pectoris (156Ϯ41%; nϭ345) and CAD (140Ϯ30%; nϭ300) patients, as well as healthy control subjects (110Ϯ17%; nϭ394).…”