Relationship of Thrombus Healing to Underlying Plaque Morphology in Sudden Coronary Death
Miranda C.A. Kramer, MD*,
Saskia Z.H. Rittersma, MD, PhD*,
Robbert J. de Winter, MD, PhD*,
Elena R. Ladich, MD ,
David R. Fowler, MD ,
You-Hui Liang, MD ,
Robert Kutys, MS, PA ,
Naima Carter-Monroe, MD ,
Frank D. Kolodgie, PhD ,
Allard C. van der Wal, MD, PhD and
Renu Virmani, MD ,*
* Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
CVPath Institute, Gaithersburg, Maryland
Department of Pathology, University of Maryland, Baltimore, Maryland

View larger version (134K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 1 Morphology of Coronary Thrombi With Early, Late (Lytic), Infiltrating, and Healing Maturation in Plaque Rupture
(A and B) Corresponding low-power views of a human ruptured coronary lesion showing a relatively large necrotic core and superimposed thrombus (early, nonhealing, <1 day in age). (C) Higher magnification of thrombus area referenced by the inset in A showing platelets and fibrin, and focal collections of neutrophils without inflammatory cells lysis. (D and E) Rupture with a superimposed lytic thrombus (1 to 3 days in age). (F) Higher-power views of the thrombus showing nuclear debris consistent with inflammatory cell degradation; the inset shows evidence of nuclear degradation (x1,000 magnification). (G and H) Rupture with an occlusive infiltrative thrombus (4 to 7 days in age). (I) Corresponding higher-power view of an infiltrative thrombus demonstrating invading mesenchymal cells with the appearance of smooth muscle cells (SMCs) and endothelium. (J and K) Rupture with a healing thrombus (>7 days in age). (L) Higher-power view of a healing thrombus characterized by organized layers of SMCs and proteoglycan-collagen matrix. A, D, G, J: x20 magnification, hematoxylin and eosin (H&E) staining; B, E, J, K: x20 magnification, Movat Pentachrome staining; and C, F, I, L: x400 magnification, H&E staining. NC = necrotic core; Th = thrombus.
|
|

View larger version (129K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 2 Morphology of Coronary Thrombi With Early, Late (Lytic), Infiltrating, and Healing Maturation in Plaque Erosion
(A and B) Low-power view of a human coronary "lipid pool" (LP) lesion consistent with pathological intimal thickening with a nonocclusive early thrombus (<1 day of age). (C) Corresponding higher-power view within the region of the inset in A consisting of platelets, fibrin, and intact neutrophils. (D and E) Human coronary plaque erosions with a superimposed lytic thrombus (1 to 3 days in age). (F) Higher-power view of the thrombus with degrading inflammatory cells; the inset shows evidence of nuclear degradation (x1,000 magnification). (G and H) Low-power view of a fibroatheroma with a superimposed infiltrative thrombus attributed to plaque erosion (4 to 7 days in age). (I) Corresponding higher-power view of the infiltrative thrombus with invading mesenchymal cells with the morphologic appearance of SMCs and endothelial cells. (J and K) Macrophage-rich early fibroatheroma with coronary plaque erosions and superimposed healing thrombus (>7 days of age). (L) Higher-power view of the healing thrombus composed of layers of SMCs and proteoglycan-collagen matrix. A, D, G, J: x20 magnification, H&E staining; B, E, J, K: x20 magnification, Movat Pentachrome staining; and C, F, I, L: x400 magnification, H&E staining. Abbreviations as in Figure 1.
|
|

View larger version (93K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 3 Immunohistochemical Identification of Invading SMCs (Anti- -SMC Actin) and Endothelium (Microvessels, Anti-CD34) in Late-Stage Thrombi in Plaque Ruptures (Infiltrating, 4 to 7 Days of Age) and Erosions (Healing, >7 Days of Age)
(A) Higher-power view of a late-stage infiltrating thrombus in plaque rupture (Movat pentachrome, x400). (B) Area within the inset in A shows infiltrating SMCs at the plaque/thrombus interface ( -SMC actin, brownish-black reaction product, x400 magnification). (C) Similar region as B, showing numerous CD34+ microvessels within the thrombus (anti-CD34, x400 magnification). (D) Healing thrombus (>7 days in age) in plaque erosion (Movat pentachrome, x400 magnification). Note the presence of proteoglycan matrix within the deeper regions of the plaque/thrombus interface highlighted by the inset. (E) -SMC actin immunostaining showing organized layers of SMCs at the base of the thrombus (x400 magnification). (F) Similar area as in E, showing an abundance of endothelial cells with microvessels formation (anti-CD34, x400 magnification). PL = plaque substrate; other abbreviations as in Figure 1.
|
|

View larger version (18K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 4 Bar Graphs Illustrating the Frequency and Distribution of Ruptures and Erosions in the Major Coronary Arteries Relative to the Degree of Thrombus Maturation
Frequency and distribution of (A) ruptures and (B) erosions in the major coronary arteries relative to the degree of thrombus maturation. The proximal regions consisted of the first 3 cm for the right coronary artery (pRC), before the first diagonal branch for the left anterior descending artery (pLAD), and the obtuse marginal for the left circumflex artery (pLCx). The mid-segments were between the first and second diagonals for the LAD, between left obtuse marginal (LOM) 1 and LOM 2 for the LCx, and beyond 3 cm of the right coronary artery (RCA) to the right marginal branch. The solid bars represent culprit plaques with early stage thrombi (<1 day of age), whereas the unfilled (open bars) represent culprit lesions with late-stage thrombi characterized as lytic (1 to 3 days), infiltrating (4 to 7 days), or healing (>7 days of age). Note the majority of ruptures and erosions were localized to the proximal LAD or RCA where there were far greater numbers of plaque erosions with late thrombi. dLAD = distal left anterior descending coronary artery; dLCx = distal left circumflex coronary artery; dRC = distal right coronary artery; LM = left main.
|
|
|