Coronary Artery Thrombus

Article Author:
Davinder Singh
Article Editor:
Kunal Mahajan
Updated:
6/4/2019 5:49:19 PM
PubMed Link:
Coronary Artery Thrombus

Introduction

The pathogenesis of acute myocardial infarction (AMI) and unstable angina is the rupture of the coronary artery plaque resulting in acute thrombotic occlusion of a coronary artery. Thus, the thrombus forms an integral part of the atherosclerotic coronary plaques.[1] There is a consensus that intracoronary thrombus makes up a challenging target for revascularization because of its unique characteristics. It has a crucial impact on the performance and outcome of the percutaneous coronary intervention (PCI). So, it is a strong predictor of PCI induced major adverse coronary events.[2]

Etiology

The main risk factors involved in the initiation of coronary thrombus include smoking, physical inactivity, obesity, stress, family history of atherosclerosis, hyperlipidemia, diabetes mellitus, and hypertension.[3]

Epidemiology

Coronary thrombosis with myocardial infarction is a serious disease and is a major cause of morbidity and mortality worldwide.[1] It kills at least 200,000 persons a year in the United States and cripples unknown numbers.

Pathophysiology

Understanding the structure of thrombus and its physical characteristics are essential to make proper treatment choices in the revascularization of atherosclerotic lesions.[4] Following the rupture of plaque's fibrous cap, the internal necrotic core gets exposed into the arterial lumen. This contact of a highly thrombogenic subendothelial matrix with the circulating platelets and white blood cells activates the coagulation cascade. This activates the platelets and furthermore promotes their adhesion and aggregation. Activated platelets release strong mediators of vasoconstriction and aggregation like serotonin, adenosine diphosphate (ADP), thromboxane A2 (TXA2), and endothelin, among others. The released tissue factor from the subendothelial matrix directly activates the extrinsic coagulation cascade and results in fibrin accumulation. All this finally accumulates to form a thrombus which causes critical occlusion and impaired distal flow, with resultant clinical ischemic complications.[5]

Histopathology

A thrombus comprises a conglomerate of platelets, red blood cells, vasoconstrictors, and procoagulant anchored to a scaffolding matrix of crisscrossing fibrin fibers. Two distinct types of branching fibrin fibers exist. The dense, thin fibers resist deforming mechanical forces and poorly dissolved by thrombolytic agents. Thick fibrin fibers are susceptible to external mechanical forces and get dissolved by thrombolytic agents.[6][7]

History and Physical

The clinical features depend on the duration and the severity of ischemia, depending on whether the obstruction is wholly or partially occlusive, transient or persistent. In acute coronary syndrome, the patient usually presents with retrosternal chest pain, dyspnea, frequently accompanied by profuse sweating and dynamic ischemic ECG changes.

Evaluation

Various imaging modalities are available for the diagnosis of intracoronary thrombus. Many studies have shown the poor sensitivity of angiography although specificity approaches 100% while using multiple angiographic views for verification. Angiography remains the practical gold standard to recognize thrombus, showing the classic findings of reduced contrast density, staining, haziness, irregular lesion contour, filling defects or a smooth convex meniscus at the site of total thrombotic occlusion. Whenever there is doubt regarding a thrombus on angiography, one can use more sensitive techniques for its detection including the angioscopy, intravascular ultrasound and optical coherence tomography (OCT). OCT is a more recent imaging technique for accurate detection of plaque and thrombus and is rapidly gaining popularity because of its user-friendly features and remarkable imaging quality.[5][8]

Treatment / Management

Treatment involves medications and percutaneous coronary interventions. The mainstay pharmacologic therapy for management of thrombus-containing lesions includes aspirin, heparin, GP IIb/IIIa platelet receptor antagonists, thienopyridines (clopidogrel, prasugrel, ticlopidine), and direct thrombin inhibitors.

It is beneficial to decrease the thrombus burden before intervention to improve PCI results and reduce the risk of distal embolization of thrombus.

Percutaneous interventions include either mechanical thrombus extraction and/or stent implantation.

Following the publication of several landmark studies, a rekindled interest in mechanical thrombus extraction arose, especially for STEMI management. One can categorize the contemporary mechanical thrombus removal or dissolution devices into four main types according to their activation mode: (1) manual aspiration catheters, (2) power-sourced thrombectomy, (3) ultrasound-induced sonication, and (4) embolic protection.

Manual thrombus aspiration of the infarct-related vessel is a useful method for the rapid decrease in the thrombotic burden, prevention of the distal embolization of thrombus, which helps in the preservation of the microvascular integrity and reduction in infarct size. Manual thrombectomy, therefore, improves myocardial perfusion grade. TAPAS trial showed a mortality reduction, which led the guidelines to recommend routine manual aspiration. [9] However, the latest trials have shown no clear-cut benefit of routine manual aspiration in acute myocardial infarction.[10][11]

Differential Diagnosis

Coronary dissection mimics coronary thrombosis.

Staging

Grading systems are essential for the adequate assessment of thrombus burden to assist management decisions before and during interventions. The TIMI Study Group introduced the established, most commonly used thrombus grading classification. They based this method on a visual angiographic assessment of the thrombus size using a score that ranges from grade 0 to grade 5.

  • Grade 0: No angiographic characteristic of thrombus
  • Grade 1: Possibility of thrombus on angiography, decreased density, haziness, irregular lesion contour
  • Grade 2: Definite thrombus, significant filling defects, the greatest dimension is 1/2 of vessel diameter
  • Grade 3: Definite thrombus with the greatest dimension is greater than 1/2 to less than 2 vessel diameter
  • Grade 4: Definite large thrombus with the greatest dimension is greater than 2 vessel diameter
  • Grade 5: Complete thrombotic occlusion

Prognosis

Once the thrombus forms in the culprit lesion, its size determines the larger infarct size and worse left ventricular (LV) function. The thrombus size also relates to PCI-related complications such as distal embolization, as suggested in a pathologic analysis of aspirated embolized debris; which showed that the larger the thrombus volume at a culprit lesion, the larger the dimensions of the debris collected inside the filter. The dimensions of the debris predicted arteriolar occlusion.

Pearls and Other Issues

Thrombus plays a major role in the pathophysiology of acute coronary syndromes (ACS). The formation of a thrombus within a coronary artery with obstruction of coronary blood flow and reduction in oxygen supply to the myocardium produces the several ACS. It is essential to understand the structural components and burden of the thrombus to decide the strategies for revascularization. Strategies combining dietary, pharmacologic-medical, and interventional-surgical therapies have shown considerable success in the prevention and treatment of major cardiovascular events. These regimens focus on inhibiting the various pathways involved in thrombus generation. Novel strategies based on the knowledge of the biochemistry of platelet aggregation and the coagulation processes and the geometric conditions encountered in the circulation are in different stages of development and clinical trials. Advances in noninvasive imaging techniques will help to identify plaques at risk and reduce the clinical impact of atherothrombosis.

Enhancing Healthcare Team Outcomes

Many interventional cardiologists widely practice thrombus aspiration during percutaneous coronary intervention in a STEMI patient. (Level II) However, recent trials (TASTE and TOTAL) have raised doubts over its value and safety. As a result, the current guidelines do not recommend the routine use of thrombus aspiration in STEMI patients. (Level I)


References

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