CC-BY-NC-ND 4.0 · Ind J Car Dis Wom 2017; 02(03): e10-e20
DOI: 10.1055/s-0037-1607390
Interventional Rounds
Women in Cardiology and Related Sciences

Coronary Thrombus

Venkata Siva Krishna Kotapati
1  Department of Cardiology, STAR Hospitals, Hyderabad, Telangana, India
Maddury Jyotsna
2  Department of Cardiology, NIMS, Punjagutta, Hyderabad, Telangana, India
Nemani Lalita
2  Department of Cardiology, NIMS, Punjagutta, Hyderabad, Telangana, India
› Author Affiliations
Further Information

Publication History

Publication Date:
01 December 2017 (online)


Thrombus is a hallmark constituent of active, unstable atherosclerotic plaques commonly found in patients with acute coronary syndromes (ACSs). Over the past three decades, percutaneous coronary intervention (PCI) has achieved high success rates with the ever-increasing inclusion of complex target lesions.[1] However, PCI success might be limited by the presence of intracoronary thrombus that continues to be a major hazard during the intervention procedure.[2] [3] The aim of this review is to discuss the role of thrombus in the pathophysiology of ACSs; describe its morphology, its impact on interventions, and outcomes; present available modalities for its identification; delineate pharmacologic therapy; and consider the tools and techniques that may be used for thrombus removal. The impact of thrombus on coronary intervention includes the following.[4] [5] [6] [7] [8]

  1. Need for targeted treatment, which increases costs and may prolong procedures.

  2. Adverse effect on lesion, vessel, and clinical outcome during and after interventions.

  3. Increased procedure-related risk of distal embolization, “no reflow,” acute thrombotic occlusion, periprocedural myocardial infarction, need for emergency bypass surgery, myocardial infarction, and death.

  4. Predictor of major adverse coronary events, early and late stent thrombosis, and in-hospital complications, as well as risk of 6-month recurrent myocardial infarction and death.

  5. Predictor of success in selected cases of chronic total occlusion (CTO).

Pathophysiology of Thrombus

An understanding of the structure of thrombus and its multifaceted characteristics is essential for making proper management choices in the revascularization of atherosclerotic lesions and vessels. A thrombus-containing lesion is formed when the fibrous cap of an atherosclerotic plaque develops structural defects.[9] Lipid-rich lesions are vulnerable to disruption or erosion because they consist of a crescentic mass of lipids either in close contact with the vessel lumen or separated from it by a discrete component of extracellular matrix.[10] [11] Plaque disruption occurs most frequently where the fibrous cap is thinnest, most heavily infiltrated by lipid-filled macrophages (foam cells), and therefore weakest, and for eccentric plaques, this tends to be the shoulder region between the plaque and the adjacent vessel wall.[12] However, the process is not purely mechanical, but an active process is involved in the pathophysiology. Atherectomy specimens from patients with ACSs reveal areas very rich in macrophages,[13] and these cells are capable of degrading extracellular matrix by phagocytosis or secretion of proteolytic enzymes; thus, enzymes such as plasminogen activators and matrix metalloproteinases (MMPs: collagenases, gelatinases, and stromelysins) may weaken the fibrous cap and predispose it to rupture. The ensuing contact of exposed, disrupted, and highly thrombogenic subendothelial matrix and plaque with circulating platelets and white blood cells activates the coagulation cascade. The resultant platelet adhesion and aggregation lead to thrombus formation. Furthermore, released tissue factor from the arterial injury directly activates the extrinsic coagulation cascade and promotes fibrin formation. Activated platelets release powerful promoters of vasoconstriction and aggregation, including serotonin, adenosine diphosphate, thromboxane A2, oxygen-derived free radicals, endothelin, and platelet-activating factor.[14] As the thrombus accumulates to form a critical obstacle, impaired flow dynamics alongside and distal to the thrombotic lesion develop, frequently accompanied by dynamic vasoconstriction and resultant clinical ischemic events.[15]


Thrombosis–Substrate Dependent

There is striking heterogeneity in the composition of human atherosclerotic plaques, even in the same individual, and the disruption of plaques exposes different vessel wall components to blood. Data on the thrombogenicity of disrupted atherosclerotic lesions are limited. The lipid core, abundant in cholesterol ester, displayed by far the highest thrombogenicity.[16]


Thrombosis–Tissue Factor Dependent

Tissue factor (TF), a small-molecular-weight glycoprotein, initiates the extrinsic clotting cascade and is believed to be a major regulator of coagulation, hemostasis, and thrombosis. TF forms a high-affinity complex with coagulation factors VII/VIIa; TF/VIIa complex activates factors IX and X, which in turn lead to thrombin generation.[17] TF antigen is normally present only in the arterial adventitia. Platelet deposition on lipid-rich atheromatous core was more than three times greater than on adventitia, with tunica media next, then foam-cell–rich matrix and collagen-rich matrix, and normal intima least thrombogenic. The lipid-rich core also exhibits the most intense TF staining, and this observation suggests that TF is an important determinant of the thrombogenicity of human atherosclerotic lesions after spontaneous or mechanical plaque disruption. Colocalization analysis of directional coronary atherectomy specimens from patients with unstable angina pointed to a strong relationship between TF and macrophages.[18]


Thrombus in Acute Coronary Syndrome: Acute Thrombosis

Disruption of a vulnerable or unstable plaque with a subsequent change in plaque geometry and thrombosis results in a complicated lesion.[19] [20] On occasion, the clinical consequence will be unstable angina or another ACS.[19] However, it seems that such a thrombus more often causes no symptoms and, by self-organization, then contributes importantly to the progression of atherosclerosis.

The platelets sustain and amplify the coagulant response at the plaque site and release procoagulant platelet-derived microparticles. Various biochemical processes and interactions between activated platelets, red blood cells, fibrinogen, vasoconstrictors, atherosclerotic material, and the vessel wall all have a substantial impact on the fibrin network. These constituents account for the thrombus's level of activity, stability, or instability and for the overall “aggressiveness” of the thrombus as encountered during intervention. The presence and ratio of the aforementioned components lead to the formation of distinct thrombus types, each with unique rheolytic and mechanical properties. The two most prominent are the red and white thrombi. They can be detected by angioscopy,[21] and their angiographic characteristics correlate with the histology of extracted thrombi.[22] The red thrombus has a dense surface with a loose inner core. Transmission or scanning electron microscopy demonstrates loosely packed fibrin and many interspersed red blood cells. The white thrombus consists of a dense structure lacking loose inner spaces, yet it contains a high concentration of platelets with fibrin and only few red blood cells.[23] Based on the histopathologic analysis of aspirated thrombotic content, erythrocyte-rich (red) thrombus is found in approximately 35% of patients, predominately in those presenting with low Thrombolysis In Myocardial Infarction (TIMI) flow. The platelet-rich (white) thrombus is identified in 65% of cases, especially in the early hours of acute myocardial infarction.[24]

However, the fact is that in many patients the occlusive thrombus is a mixture of red and white clot, and the frequent resistance upon extraction attempts suggests that certain clots contain layers upon layers of one thrombus type interspersed with the other.[25] [26] From a clinical management viewpoint, coronary risk factors such as hypercholesterolemia, smoking, and male sex adversely influence plaque morphology in patients with ACSs and are associated with a higher frequency of thrombus.