Erosions and late-stage thrombi more prevalent in women and younger sudden death victims

There may be important distinguishing features in the underlying substrate and thrombi in women and younger people who die suddenly from coronary disease, according to a new expedited publication in the Journal of the American College of Cardiology.

The study was premised on observations that plaque erosion rather than rupture accounts for a quarter of all in-hospital AMI deaths, particularly in women and younger men. Thrombi associated with plaque rupture are fresher and show a lack of healing, according to the investigators. By contrast, a large proportion of thrombi associated with erosions are in the late stage of healing.

A team led by Renu Virmani studied the relationship of thrombus healing to the underlying plaque in 111 victims of sudden coronary death, including 65 ruptures and 50 erosions. The researchers classified thrombus healing in each case as early ( 1 day), late (1 to 3 days), infiltrating (4 to 7 days), or healing ( 7 days). Overall, late-stage thrombi were found in 69% of the culprit plaques. 88% of the women had a late-stage thrombi, and accordingly they were more likely to have had erosion.

The authors observe that ruptures are more likely to be lethal in patients with more severe narrowing. By contrast, narrow lesions are not as prevalent in patients with erosions, since the thrombi may  “have more time to evolve and often show greater healing either at the time of AMI or sudden death.” Further, note the authors, “greater thrombus organization in erosion occurs in the deeper regions of the thrombus where it mixes with plaque despite a persistence of platelet aggregates near the luminal surface, where this dynamic process might constitute a persistent nidus for distal embolization.”

PK Shah sent the following commentary to CardioBrief:

Kramer and colleagues from Dr Renu Virmani’s group have studied 111 victims of sudden cardiac death to evaluate age of thrombus and its relationship to underlying plaque features. Age of thrombus was determined by detailed histology as were the plaque characterisitics; 65 thrombi were from plaque rupture and 50 thrombi were implicated to plaque erosion. Authors noted that plaque erosion related thrombi showed a high prevalence of varying degress of organization and healing suggesting that a large proportion were more than 1 day old; similar features were noted in 14 of 64 thrombi related to plaque rupture. Healing rupture related trombi had underlying plaques with greater IEL expansion and increased macrophage infiltration.

The authors conclude that sudden death related to coronary thrombosis , especially where plaque erosion is the substrate may be preceded by days of thrombosis that is healing until the final event triggers the presumed arrythmia; something that has also been noted in AMI patients using histology of aspirated thrombi. Although these findings are interesting they confirm previously reported data. Erling Falk showed layered thrombi of varying ages in unstable angina patients dying from CAD many years ago as well. The potentilly new finding is that erosion induced thrombi show a higher prevalence of healing compared to rupture induced thrombi. One wonders whether the morphologic features of plaque erosion may actually be the result of waves of thrombosis and healing that create a proteoglycan rich plaque . Authors also have not looked for microemboli which may be the final triggers of sudden death.

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