Coronary Thrombosis--The Culprit Is Not Just Plaque Rupture

October 09, 2009

October 9, 2009 (Amsterdam, the Netherlands and Gaithersburg, Maryland) — The coronary thrombosis that causes sudden coronary deaths is not always caused by a plaque rupture. In many cases, such thromboses appear to be made up of older clot tissue that is believed to originate from erosions of the vessel wall, and these erosions may need a completely different approach to treatment, a new study suggests [1].

The study, published online on October 7, 2009, in the Journal of the American College of Cardiology, also found that these erosion-type clots were more likely to occur in women, particularly young women, who had suffered sudden cardiac death than in men.

Senior author of the study, Dr Renu Virmani (CVPath Institute, Gaithersburg, MD), commented to heartwire : "We appear to be looking at completely different etiologies behind the two types of clots. Conventional treatment of coronary heart disease is all geared to the plaque-rupture scenario. But actually, the erosion type of clot seems to be associated with a worse outcome. Although atherosclerosis is probably involved in erosions, this is only part of the story, and we believe that vasospasm may be the underlying cause of these clots forming. This would suggest that a whole new approach to treatment needs to be investigated."

Virmani explained to heartwire that the popular view of coronary thrombosis is that it is caused by rupture of the thin fibrous cap on the atherosclerotic plaque, exposing the necrotic plaque core, which forms the clot. But the erosion pathology, in which the endothelial cells on the vessel wall are eroded, leaving a raw surface that causes a thrombus to form in the lumen of the artery, may be just as, if not more, important.

May Explain Why Women Have Worse Outcomes

She believes that these observations may help to explain why women who have an MI tend to have worse outcome than men--because the erosion type of clot appears to be more deadly and occurs more often in women. "In women under 50 years of age, 80% of coronary thrombi are of the erosion type. Beyond 60, women follow a more similar pattern to men and have more rupture-type thrombi. In men under 40 years of age, the figures are more like 50% erosions and 50% ruptures, then after 40, men will have predominantly ruptures," she says.

She notes that the group of people who have erosions (young women and some young men) are very poorly studied. "It has long been suspected that chest pain in women may be different from that in men, but this has not been well investigated, and we have made very little progress in this area. I think we are talking about a different disease process. Yes, there is some plaque buildup, but this may not be severe. I think it is more of a vasospastic problem, and smoking and the contraceptive pill may also contribute. It would be very difficult to diagnose, because there wouldn't be severe narrowings, but perhaps we should be concentrating more on analyzing the blood for activated platelets and looking for clots forming in the arterial walls in this group."

Virmani suggests that in future there should be a better referral system for young women who complain of chest pain. "At present, physicians often tell them that they just have anxiety, but we should be thinking about specific chest-pain centers for women, which would be more focused on looking for the erosion type of clots." And different strategies to protect against the development of such clots may also be needed, which Virmani says may involve agents to relax the arteries. "Cholesterol is also involved in these clots, but probably not to the same degree as a clot caused by a ruptured plaque," she adds.

Older Thrombi, Higher Risk of Death

In a previous study, a team led by Dr Miranda Kramer (Academic Medical Center, Amsterdam, the Netherlands), who is also lead author of the current paper, showed that when aspirated thrombi from MI victims were classified by histology, those with older thrombi (more than one day old) seemed to have a worse outcome and a higher risk of death than those who had thrombi which were less than one day old. Women were also more likely to have the older thrombi than men, Virmani noted.

"We needed to know how these newer and older thrombi corresponded to ruptures and erosions," she said. With this goal in mind, the Kramer group teamed up with Virmani and colleagues for the present study. In the current study, the researchers analyzed thrombi from coronary lesions taken from 111 sudden cardiac death patients. Plaques with acute coronary thrombi were categorized as plaque rupture or erosion. Ruptures showed areas of necrosis underlying a thin disrupted fibrous cap with a superimposed luminal thrombus, whereas eroded plaque showed surface thrombi but no cap disruption. Using this definition, 65 of the lesions had thrombi originating from ruptures, and 50 were from erosions.

Is Your Thrombus Organized?

Thrombus healing was classified as early or late. Early-stage thrombus was defined as clot of less than one day old, and late-stage thrombus was defined as clot older than one day. The researchers explain that the age of the clot can be ascertained from its content--a relatively new clot will be made up of platelets mixed with fibrin and intact neutrophils, whereas clots of one to three days old will contain degraded acute inflammatory cells. After four days, there will be some smooth-muscle cells and/or endothelial cells present, and after seven days (when the thrombus is classified as healing), a proteoglycan matrix forms. An older clot is also referred to as an "organizing" thrombus.

Erosions Tended to Be Later-Stage Thrombi

Results showed that late-stage thrombi were identified in 79 of the 115 (69%) culprit plaques. When looking at the difference in stage of thrombus between clots classified as ruptures or erosions, the researchers found that in ruptures, nearly one-half of thrombi were classed as early stage, with the remaining (50%) categorized as late stage. In contrast, more than 85% of thrombi in clots classified as erosions exhibited later-stage characteristics.

Kramer et al conclude: "There is considerable evidence to indicate that the etiology and pathogenesis of initiating event(s) causing rupture or erosion are distinct regarding inflammation, remodeling, and growth rates of the underlying plaque. The current data widen this view, where coronary thrombi in fatal erosions are in later stages of maturation as compared with ruptures. Considering that STEMI patients with healing thrombi of more than one day have poorer prognosis, the present findings that erosions are the main cause of healing thrombi--which occur predominantly in women and younger men--would further indicate that women and younger men might require different strategies of treatment."


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: