Triple coronary thrombosis: autopsy case and literature review

Abstract

Triple coronary artery thrombosis is a rare cause of acute myocardial infarction, and is associated with high mortality. Only a few cases of simultaneous multiple-vessel coronary thrombosis have been reported in the medical literature. This paper reports a unique case of sudden cardiac death in 36-year-old man without relevant risk factors who suffered from acute myocardial infarction due to simultaneous triple coronary artery thrombosis. Autopsy and histopathology examinations revealed near-total thrombotic occlusion in all three main coronary arteries. While the exact mechanism behind the simultaneous formation of these thrombi remains unclear, this paper discusses certain risk factors that may contribute to multiple coronary thrombosis. A review of previously reported cases of coronary thrombosis involving all three major coronary arteries in the literature is also provided to contribute to the understanding of this rare and potentially fatal condition. Obtaining a detailed medical and family history, collecting and saving blood samples for potential genetic analyses, and testing for Novel Coronavirus disease could be beneficial in cases of multiple coronary artery thrombosis to detect a potential underlying cause and provide prevention to family members at risk.

Introduction

Acute myocardial infarction (MI) is typically a complication of coronary artery disease. The most common risk factors are hypertension, dyslipidemia, diabetes mellitus, smoking, and obesity. Although multivessel coronary atherosclerotic disease is typically present in patients with acute ST-segment elevation myocardial infarction (STEMI), acute STEMI is usually a result of atheromatous plaque rupture with subsequent thrombotic occlusion in one coronary artery [1], and concomitant thrombosis of more than one coronary artery is exceptional. While the exact pathophysiologic mechanism of the simultaneous formation of multiple thrombi is still unclear, potential mechanisms have been proposed. Simultaneous rupture of multiple coronary plaques at one time, leading to the simultaneous formation of multiple thrombi is one of the explanations. It can result from an extensive inflammatory process (panarteritis) or from a catecholamine surge, which results in platelet activation [2]. Another proposed mechanism is that plaque rupture with subsequent thrombus formation in one vessel leads to cardiogenic shock and impaired blood flow to other coronary arteries, which results in secondary acute thrombosis in multiple arteries [3].

Multivessel thrombosis cases are associated with a high incidence of complications including cardiogenic shock and ventricular arrhythmias, (4–5) tend to have a poor prognosis and commonly present as sudden cardiac death in the hospital or at the scene.

This report describes the case of a 36-year-old obese Asian male with no other known medical history or risk factors, who died suddenly due to triple coronary artery thrombosis. A discussion of possible risk factors and a review of the literature are reported.

Case report

A 36-year-old South Asian man was witnessed collapsing by his coworkers while attempting to get into his vehicle. Cardiopulmonary resuscitation was performed, and the Emergency Services responded to the scene and transported him to the hospital, where he was pronounced dead despite the resuscitative efforts.

According to coworkers, the deceased complained of chest pain all day but refused to visit the hospital. He took Tylenol for pain. A family member also mentioned that the subject frequently complained of chest pain recently but refused to seek medical attention. Other than that, he had no medical history and no significant risk factors for coronary artery disease. He had no history of smoking, alcohol, or drug use, and was taking no medications other than Tylenol. He had no reported significant family history of cardiovascular disease, sudden cardiac death, or hematological or coagulation disorders. Additionally, there was no reported history of recent respiratory problems, recent flu-like symptoms, contact with sick individuals, or COVID-19 exposure.

Owing to the sudden and unexpected nature of death, a forensic autopsy was performed to determine the cause and manner of death.

Autopsy and microscopic findings

At autopsy, the body was that of a Class I obese adult male weighing 108 kg and measuring 178 cm in height, with a body mass index (BMI) of 34.1 kg/m².

The external examination was negative for traumatic injuries. Gross examination of the heart revealed a 458 g organ (reference range [RR]; 331–591 g), which is in line with the expected weight for individuals of the same sex, age, height, and weight [6]. There were no evident size or shape abnormalities. The coronary arteries had normal origins and were normally distributed on the epicardial surface. Serial sectioning of the coronary arteries revealed nearly total occlusion of all vessels by thrombi in different stages of organization with aneurysm formation at the sites of thrombosis (Fig. 1). The right coronary artery (RCA) contained multifocal organizing thrombi, with a maximum proximal arterial dilation of 1.3 cm and background atherosclerosis obstructing up to 50% of the lumen. The left anterior descending artery (LAD) contained an organizing thrombus with proximal arterial dilation up to 0.9 cm and background atherosclerosis obstructing up to 25% of the lumen. The left circumflex artery (LCX) showed an organizing thrombus with proximal arterial dilation up to 0.6 cm and background atherosclerosis obstructing up to 25% of the lumen.

Fig. 1

Gross examination of the coronary arteries showing near total occlusion by multiple thrombi in different stages of organization with aneurysm formation at the sites of thrombosis

The heart was then dissected following the ‘short-axis method’, consisting of 0.8–1.5 cm thick multiple transverse cuts performed from the cardiac apex to the base, parallel to the atrioventricular groove. Examination of the cut sections revealed a fibrotic scar of the posterior left ventricle measuring 3.3 cm in greatest dimension. The left ventricular wall was 1.3 cm thick, the right ventricular wall was 0.3 cm thick, and the interventricular septum was 1.5 cm thick.

Sections of the myocardium from the left ventricle, right ventricle, and interventricular septum, and from the coronary arteries with occluding thrombi were submitted for microscopic examination.

On microscopic examination, sections from the coronary arteries revealed complex organized thrombi at various stages of organization with associated chronic inflammation and granulation tissue. There was associated chronic inflammation of the vascular media and adventitia with lymphocytic aggregates on the external surface of the adventitia. (Fig. 2)

Fig. 2

Microscopic examination of the coronary arteries showing complex organized thrombi at various stages of organization with associated chronic inflammation and granulation tissue, chronic inflammation of the vascular media and adventitia with lymphocytic aggregates on the external surface of the adventitia (A-C, H&E, 40X; D, H&E, 100X)

Sections of the left ventricular wall revealed interstitial fibrosis and area of subendocardial fibrosis. In addition, hypertrophic cardiomyocytes with enlarged “box-car” nuclei and multifocal contraction band necrosis were present throughout the ventricular wall.

The gross and microscopic heart findings were consistent with acute myocardial infarction. The findings also suggested remote myocardial infarction, and hypertensive-like changes.

The pulmonary parenchyma was pink-red to deep purple and edematous, exhibiting moderate amounts of bloody fluid upon sectioning. The right lung weighed 920 g; the left lung weighed 754 g. The liver weighed 2225 g with moderately soft, yellow-brown fatty parenchyma. All other organs, except for the heart, were grossly unremarkable and raised no concerns for underlying pathology.

Toxicology tests of postmortem peripheral blood were negative for alcohol, the tested drugs, and the prescribed medications.

Based on the available evidence, the cause of death was certified as acute myocardial infarction due to multivessel coronary artery thrombosis secondary to coronary artery disease, and obesity was considered a significant contributing condition. The manner of death was natural.

Discussion

Simultaneous triple coronary artery thrombosis is a rare condition associated with a high mortality rate and commonly presents as sudden cardiac death. While several clinical papers have been published in the literature, autopsy-confirmed cases of simultaneous triple-vessel coronary thrombosis are rarely reported. The young age of the subject, the absence of major risk factors for coronary artery disease other than obesity, and recent complaints of episodic chest pain suggest a potential undiagnosed underlying pathology of the coronary arteries. Therefore, further investigation is warranted.

Multiple coronary artery thrombosis is exceptional. In a study by Pollak et al. only 18 out of 711 (2.5%) STEMI patients at the time of percutaneous coronary intervention (PCI) had angiographic findings of thrombosis in multiple culprit arteries [4]. The authors emphasized the clinical severity of this condition, and suggested that patients with multiple culprit artery-involved STEMIs were prone to present with sudden cardiac death, precluding angiography [4].

Certain factors are thought to increase the risk of multiple coronary thrombosis, including extensive coronary artery disease, dyslipidemia, a history of smoking, diabetes mellitus, prolonged coronary vasospasm, (7–8) cocaine use, (9–10) cannabis and synthetic cannabinoid use, (11–12) hormonal therapy [13], heparin-induced thrombocytopenia, (14–15) essential thrombocytemia [16,17,18], hypercoagulability of malignancy [19], hyperhomocysteinemia [20], endocarditis, coronavirus disease 2019 and others.

In the reported case, the only major risk factor present was obesity (BMI 34.1 kg/m2). A meta-analysis of more than 300 000 adults with 18 000 coronary artery disease (CAD) events demonstrated that BMIs in the overweight and obese ranges were associated with elevated CAD risk [21].

Based on the Poiseuille-Hagen equation, which describes the flow of a fluid through a cylindrical vessel, the key factor affecting blood flow in the vessel is its radius. Even small changes in the vessel’s radius have a significant impact on the flow. In our case, atherosclerotic coronary artery stenosis of up to 50% was noted, meaning that the effective radius of the artery was reduced by 50%. Since flow is proportional to the fourth power of the radius, even a 50% reduction in the radius leads to a much larger reduction in flow. If the radius is reduced to half its original size, the flow will decrease to 1/16, or 6.25% of the original flow, assuming all other factors (pressure difference, viscosity, and vessel length) remain constant. This significantly impacts blood flow, predisposing to thrombosis and potentially leading to ischemia.

A potential relationship between coronary artery thrombosis and Coronavirus disease 2019 (COVID-19) infection has been proposed. Previous studies have shown that multiple coronary vessel thrombosis events could be associated with COVID-19 infection [22,23,24,25]. In the study by Choudry et al., 115 STEMI patients were observed, and a dense thrombus burden, higher rates of multivessel thrombosis, and stent thrombosis and poorer outcomes were reported in the COVID-19-positive group [26].

Postmortem COVID-19 testing is not performed routinely in all autopsy examinations but generally only when there is a strong suspicion of infection. In the present case, a postmortem COVID-19 test was not performed, because the infection risk was considered low, so the potential relationship between viral infection and coronary artery thrombosis cannot be completely excluded. However, when multiple coronary thromboses are found at autopsy, postmortem testing for COVID-19 can be beneficial, especially if the subject is young.

Multiple coronary vessel thrombosis can also be associated with underlying genetic conditions, (27–28) such as hyperhomocysteinemia (20, 29–30) (e.g., gene mutations in methylenetetrahydrofolate reductase and cystathionine β-synthase), and antithrombin III deficiency [31]. Some inherited thrombophilias (protein C deficiency, protein S deficiency, factor V Leiden etc.) [32] were suggested to have a modest association with an increased tendency toward arterial thrombosis (including MI) in young individuals and might play a role in multiple coronary thrombosis; however, further research is needed.

In sudden deaths of young individuals, it is generally suggested to collect a sample of blood during autopsy in a purple (lavender) top tube for possible future genetic testing, since having the sample available allows the decedent family to choose whether or not to request genetic analysis. Moreover, it is important to notify the decedent’s family of the possibility of underlying genetic conditions that may affect other family members, and suggest considering a genetic consultation. Unfortunately, owing to a lack of understanding of the medical consequences of these conditions and the high cost of genetic testing, families rarely proceed with recommended testing. However, it is still the responsibility of the medical examiner/coroner to explain and inform the family about all the benefits of testing and the risks of not testing and the impact it can have on the deceased family’s life.

A review of the medical literature on simultaneous coronary thrombosis involving all three major coronary arteries in the English language was performed. The keywords “triple coronary thrombosis”, “multiple coronary thrombosis”, “three-vessel coronary thrombosis”, and “triple-vessel coronary thrombosis” were searched via PubMed and Google Scholar, for articles published between 1964 and 2024.

Six papers met the search criteria. In all patients, all three major coronary arteries were affected by thrombosis, which was identified during angiographic studies or autopsies. LAD, LCX, RCA and their branches were typically involved. Chest pain was present in all patients. All the subjects were male, and their ages varied from 33 to 62 years (mean 46.3, median 46). Three out of six patients survived. Three out of six patients died, with a partial autopsy revealing triple coronary artery thrombosis in one patient, potentially linked to synthetic cannabinoid use [11].

The most common observed risk factors were: hypertension (3 out of 6), smoking (3 out of 6), type II diabetes mellitus (2 out of 6), and previous myocardial infarction (2 out of 6). A summary of the literature review is reported in Table 1.

Conclusion

Simultaneous triple coronary artery thrombosis is a rare condition, associated with a high mortality rate. It is important to emphasize that, especially in young and apparently healthy individuals with no relevant risk factors, multiple coronary artery thrombosis can be a sign of an underlying unknown condition or risk factor. Asking the decedent’s family and their primary care physician for a detailed medical history may reveal clues related to catastrophic and unexpected postmortem coronary artery findings.

Moreover, the possibility that the underlying genetic condition may affect other family members of the decedent needs to be considered. Therefore, explaining the autopsy results to family members in an easy and understandable way is mandatory, and suggesting that they speak with their family medicine doctor to determine the need for possible genetic testing is an essential responsibility of medical examiners in such cases. To allow for future genetic testing, in sudden unexpected deaths with rare findings it is always suggested to collect and save a blood sample in purple (lavender) tubes in individuals younger than 40 years.

Finally, given the recent association between COVID-19 infection and an increased risk of thrombosis, including multivessel thrombosis, testing for COVID-19 in all patients with multiple coronary thrombosis may be beneficial.

Table 1 Summary of coronary thrombosis cases involving all three major coronary arteries