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Thrombus Grading for Coronary Interventions

The Role of Contemporary Classifications
On Topaz; Allyne Topaz; Kristine Owen

Interv Cardiol. 2011;3(6):705-712.

Abstract and Introduction

Abstract

A thrombus is an important component of the active and unstable atherosclerotic coronary plaque. A thrombus exhibits unique physical properties and commonly displays profound abnormal vascular behavior. The presence of a thrombus has been recognized as a strong predictor of significant risk for complications and poor outcome in percutaneous interventions and imposes technical challenges regarding its removal from the vasculature. Thus, angiographic detection of a thrombus serves as a procedure hallmark, which requires careful consideration for selection of an appropriate treatment approach. The grading of an underlying thrombus content and its burden on coronary flow can be assessed by various classifications. The aim of this article is to describe the pathophysiologic components of thrombus formation and to delineate the role of corresponding contemporary classifications that can be used for its assessment. Incorporating thrombus classification into the decision-making process in percutaneous coronary revascularization can enhance the yield of procedures and ensure high-quality interventions.

Introduction

Determining the appropriate management for patients with acute and chronic ischemic coronary syndromes requires careful assessment of the risk of mortality and adverse ischemic events.[1] The morphology of the targeted plaque and its composites needs to be taken into consideration once a decision has been made to proceed with percutaneous coronary intervention (PCI). Thrombus are an integral component of atherosclerotic coronary plaques, which are frequently encountered in patients with unstable angina and acute myocardial infarction (AMI).[2,3] There is a consensus that the presence of intracoronary thrombus constitutes a challenging target for revascularization because of its unique physical properties and pathologic vascular characteristics. Due to the crucial impact of thrombus on the performance and the outcome of PCI, the quest for an optional treatment for thrombotic lesions continues.[4] To date, thrombus remains a strong predictor of PCI-induced major adverse coronary events, development of acute and late stent thrombosis and increased rate of in-hospital complications, as well as AMI and death at 6 months.[5–7] Harjai et al. investigated the incidence of intracoronary thrombus after primary PCI for AMI and analyzed its impact on the presence of residual thrombus post-intervention for acute coronary syndromes.[8] They found that residual thrombus is relatively uncommon; however, in those patients with Thrombolysis In Myocardial Infarction (TIMI) 2 or TIMI 3 flow post-PCI the presence of intracoronary thrombus is associated with worse cardiovascular outcomes.

The response of thrombus to standard management by pharmacotherapy and interventional equipment varies, and at times, is unpredictable. Plausibly, the classification of thrombus according to its burden is warranted because it focuses on one of the most important components, of the active, unstable atherosclerotic plaques. Thrombus classification can also enhance the yield of procedures and ensure high-quality interventions.[9] Intriguingly, despite the understanding of the structural complexity of thrombus[10] and its significant impact on PCI outcome,[11,12] the literature reveals a paucity of publications regarding PCI for ischemic coronary syndromes reporting the presence of angiographic thrombus or grade of its burden.[13] Therefore, the aim of this article is to delineate the pathophysiologic aspects of thrombus formation and to detail the contemporary classifications of thrombus grading.

Pathophysiologic Aspects of Thrombus Formation

The fundamental pathologic processes accounting for thrombus formation begin when disrupted, highly thrombogenic subendothelial matrix and plaque are exposed to circulating platelets and white blood cells. This activates the coagulation cascade and platelet adhesion and aggregation ensue, leading to the creation of thrombus. Concomitant release of tissue factor from the arterial injury site activates the extrinsic coagulation cascade and promotes fibrin formation. The activated platelets release powerful vasoconstrictive compounds and aggregation agents such as serotonin, adenosine diphosphate, thromboxane A2, oxygen-derived free radicals, endothelin and platelet-activating factor.[14] As thrombus accumulates (Figure 1) flow dynamics at the thrombotic lesion and distally to this site are significantly impaired. Clinically, the accompanying vasoconstriction further impairs myocardial perfusion and enhances development of ischemic coronary events.[15] From a technical point of view, during PCIs operators frequently encounter considerable friability of the thrombus at the targeted lesion. However, at times the opposite reaction is observed, with the thrombus resisting removal attempts via extraction techniques. Such structural instability and/or rigidity occurs while the thrombus loosely or firmly adheres to the underlying atherosclerotic plaque and vessel wall. This seemingly contradictory characteristics of thrombus – either marked friability or a resistive response – stems from cumulative effects that are generated by an assortment of components within the thrombus. Structurally, the thrombus is supported by framework made of fibrin fibers.[16] Two distinct types of branching fibrin fibers are organized in a 3D network. The dense, thin fibers resist deforming mechanical forces (i.e., balloons or stents) and are poorly dissolved by thrombolytic agents. On the other hand, thick fibrin fibers are more susceptible to the effects of external mechanical forces and are readily dissolved by thrombolytic therapy.[17] Platelets, red blood cells, procoagulant compounds and vasoconstrictors are anchored to the matrix of the crisscrossing fibers. Abnormalities in platelet function can persist and predict ensuing adverse clinical events following PCI.[18] In patients presenting with acute coronary syndromes, the platelets that adhere to the thrombus exert a significant increase in contractile force. This leads to increased platelet aggregation and the entire thrombotic structure exhibits increased elastic modulus.[19] The platelets sustain and amplify the coagulant response at the plaque site and further release procoagulant platelet-derived microparticles. Prominent factors accounting for the formation of a high-grade thrombus burden include hyperglycemia and an increased white blood cell count.[20] Both factors additionally portend the lack of ST-segment resolution and are associated with worse PCI outcome.[21] A direct relationship between high thrombus content and large vessel size has been suspected for a long time, however, it has not been uniformly confirmed.





Figure 1.

Histopathology of a cross-section of a heavy burden occlusive coronary thrombus.
T: Thrombus.
Image courtesy of Shannon Mackey-Bojack, Jesse Edwards Registry of Cardiovascular Disease, Nasseff Heart Center, United Hospitals, University of Minnesota School of Medicine, St Paul, MN, USA.



The 'Angry Thrombus' Phenomenon

The 'angry thrombus' is an angiographic clinical term that describes a unique pathologic and aggressive thrombus-accumulation, which complicates PCI in thrombus containing lesions.[4] Considered by experienced interventionalists as an ominous sign of impending complication, this type of aggressive clot formation can occur at any stage of coronary or peripheral interventions. Once an 'angry thrombus' is formed it rapidly aggregates at the target lesion and beyond, frequently protruding (proximally and distally) deeply into the treated vessel.[22] Noteworthy, an 'angry thrombus' can easily reach a size of TIMI thrombus grade 3–5. It imposes considerable danger of clot fragmentation followed by downstream embolization and occlusion of smaller arteries. Left untreated, the 'angry thrombus' rapidly causes cessation of antegrade flow, distal embolization and marked decrease in myocardial perfusion. This process frequently leads to AMI accompanied by severe hemodynamic instability. Commonly, the 'angry thrombus' resists the standard pharmacologic regimen, balloon angioplasty and stenting.[23] The correct and best method for the management of this adverse thrombotic process initially requires an accurate assessment of the thrombus location and size. Angiographic identification of a rapid increase in the thrombus volume should be followed by expeditious clot removal. In most cases an aggressive, angry thrombus does not responds readily to aspiration catheters and requires mechanical thrombectomy and enhanced pharmacotherapy to promptly achieve restoration of antegrade flow and myocardial perfusion.[22]

Coronary Thrombus Grading Systems

Thrombus grading scales are essential tools used for qualification and quantification of the thrombus burden. They provide a platform for clinical assessment and subsequently effect management decisions prior to and during interventions. The widely used TIMI thrombus grading scale was originally created by the TIMI study group investigators.[24] The introduction of this universal classification reflected a growing recognition among cardiologists that the yield of thrombolytic therapy for evolving AMI was defined by different size and burden of intracoronary thrombi. Altogether, the TIMI classification relies on the angiographic assessment of the presence of thrombus and its relative size, utilizing a simple score ranging from grade 0 (no thrombus), to grade 5 (very large thrombus content that completely occludes vessel flow; ).


Box 1. The TIMI thrombus scale.




•Grade 0: no angiographic evidence of thrombus


•Grade 1: angiographic features suggestive

Kết quả (Việt) 1:

www.Medscape.com Thrombus chấm điểm cho các biện pháp can thiệp động mạch vànhVai trò của các phân loại hiện đạiTrên Topaz; Allyne Topaz; Kristine OwenInterv Cardiol. 2011; 3 (6): 705-712. Trừu tượng và giới thiệuTóm tắtThrombus một là một thành phần quan trọng của các hoạt động và không ổn định atherosclerotic mạch vành mảng bám. Thrombus một cuộc triển lãm đặc tính vật lý độc đáo và thường hiển thị sâu sắc đến hành vi bất thường mạch máu. Sự hiện diện của một thrombus đã được công nhận là một dự báo mạnh mẽ của các rủi ro đáng kể cho các biến chứng và các kết quả nghèo trong chữa can thiệp và áp đặt các thách thức kỹ thuật về gỡ bỏ nó từ các mạch máu. Vì thế, angiographic phát hiện của một thrombus phục vụ như một tiêu chuẩn thủ tục, yêu cầu xem xét cẩn thận để lựa chọn của một cách tiếp cận điều trị thích hợp. Phân loại của một nội dung thrombus tiềm ẩn và gánh nặng của nó trên mạch vành flow có thể được đánh giá bởi các phân loại khác nhau. Mục đích của bài viết này là để mô tả các thành phần pathophysiologic thrombus hình thành và để phân định vai trò của phân loại hiện đại tương ứng có thể được sử dụng để đánh giá của nó. Kết hợp thrombus phân loại vào quá trình ra quyết định trong revascularization mạch vành qua da có thể nâng cao năng suất của thủ tục và đảm bảo chất lượng cao can thiệp.Giới thiệuXác định việc quản lý thích hợp cho các bệnh nhân với hội chứng thiếu máu cục bộ mạch vành cấp tính và mãn tính đòi hỏi phải cẩn thận đánh giá nguy cơ tử vong và bất lợi các sự kiện thiếu máu cục bộ. [1] các hình thái của các mảng bám mục tiêu và vật liệu tổng hợp của nó cần phải được đưa vào xem xét khi quyết định đã được thực hiện để tiến hành với sự can thiệp mạch vành qua da (PCI). Thrombus là một thành phần không thể tách rời của mảng mạch vành atherosclerotic, thường xuyên gặp phải ở những bệnh nhân với đau thắt ngực không ổn định và nhồi máu cơ tim cấp tính (AMI). [2,3] đó là một sự đồng thuận rằng sự hiện diện của intracoronary thrombus tạo thành một mục tiêu đầy thách thức cho revascularization vì các tính chất vật lý độc đáo và đặc điểm bệnh lý mạch máu. Do tác động quan trọng của thrombus về hiệu suất và kết quả của PCI, nhiệm vụ cho một điều trị tùy chọn cho bớt tổn thương tiếp tục. [4] đến nay, thrombus vẫn còn một dự báo mạnh mẽ của PCI gây ra bất lợi mạch vành các sự kiện lớn, phát triển cấp tính và cuối stent huyết khối và tăng tốc độ biến chứng trong bệnh viện, cũng như AMI và cái chết lúc 6 tháng. [5-7] Harjai et al. điều tra tỷ lệ intracoronary thrombus sau khi chính PCI cho AMI và phân tích tác động của nó trên sự hiện diện của sự can thiệp sau dư thrombus cho hội chứng mạch vành cấp tính. [8] họ đã tìm thấy rằng thrombus dư là tương đối phổ biến; Tuy nhiên, ở những bệnh nhân với Thrombolysis trong nhồi máu cơ tim (TIMI) 2 hoặc TIMI 3 dòng chảy bài-PCI sự hiện diện của intracoronary thrombus được kết hợp với kết quả tồi tệ hơn tim mạch.Các phản ứng của thrombus với tiêu chuẩn quản lý bởi pharmacotherapy và can thiệp thiết bị khác nhau, và đôi khi, là không thể đoán trước. Plausibly, phân loại thrombus theo gánh nặng của nó được bảo hành bởi vì nó tập trung vào một trong các thành phần quan trọng nhất, của các hoạt động, không ổn định atherosclerotic mảng. Phân loại thrombus cũng có thể nâng cao năng suất của thủ tục và đảm bảo chất lượng cao can thiệp. [9] intriguingly, mặc dù sự hiểu biết về cấu trúc phức tạp của thrombus [10] và của nó tác động đáng kể vào kết quả PCI, [11,12] các tài liệu cho thấy một paucity của Ấn phẩm liên quan đến PCI cho hội chứng mạch vành thiếu máu cục bộ báo cáo sự hiện diện của angiographic thrombus hoặc lớp của gánh nặng của nó. [13] do đó, mục đích của bài viết này là để phân định các khía cạnh pathophysiologic thrombus hình thành và để xem chi tiết các phân loại hiện đại của thrombus chấm điểm.Các khía cạnh pathophysiologic Thrombus hình thànhThe fundamental pathologic processes accounting for thrombus formation begin when disrupted, highly thrombogenic subendothelial matrix and plaque are exposed to circulating platelets and white blood cells. This activates the coagulation cascade and platelet adhesion and aggregation ensue, leading to the creation of thrombus. Concomitant release of tissue factor from the arterial injury site activates the extrinsic coagulation cascade and promotes fibrin formation. The activated platelets release powerful vasoconstrictive compounds and aggregation agents such as serotonin, adenosine diphosphate, thromboxane A2, oxygen-derived free radicals, endothelin and platelet-activating factor.[14] As thrombus accumulates (Figure 1) flow dynamics at the thrombotic lesion and distally to this site are significantly impaired. Clinically, the accompanying vasoconstriction further impairs myocardial perfusion and enhances development of ischemic coronary events.[15] From a technical point of view, during PCIs operators frequently encounter considerable friability of the thrombus at the targeted lesion. However, at times the opposite reaction is observed, with the thrombus resisting removal attempts via extraction techniques. Such structural instability and/or rigidity occurs while the thrombus loosely or firmly adheres to the underlying atherosclerotic plaque and vessel wall. This seemingly contradictory characteristics of thrombus – either marked friability or a resistive response – stems from cumulative effects that are generated by an assortment of components within the thrombus. Structurally, the thrombus is supported by framework made of fibrin fibers.[16] Two distinct types of branching fibrin fibers are organized in a 3D network. The dense, thin fibers resist deforming mechanical forces (i.e., balloons or stents) and are poorly dissolved by thrombolytic agents. On the other hand, thick fibrin fibers are more susceptible to the effects of external mechanical forces and are readily dissolved by thrombolytic therapy.[17] Platelets, red blood cells, procoagulant compounds and vasoconstrictors are anchored to the matrix of the crisscrossing fibers. Abnormalities in platelet function can persist and predict ensuing adverse clinical events following PCI.[18] In patients presenting with acute coronary syndromes, the platelets that adhere to the thrombus exert a significant increase in contractile force. This leads to increased platelet aggregation and the entire thrombotic structure exhibits increased elastic modulus.[19] The platelets sustain and amplify the coagulant response at the plaque site and further release procoagulant platelet-derived microparticles. Prominent factors accounting for the formation of a high-grade thrombus burden include hyperglycemia and an increased white blood cell count.[20] Both factors additionally portend the lack of ST-segment resolution and are associated with worse PCI outcome.[21] A direct relationship between high thrombus content and large vessel size has been suspected for a long time, however, it has not been uniformly confirmed.Hình 1. Bệnh của một mặt cắt ngang của một gánh nặng occlusive mạch vành thrombus. T: thrombus. Hình ảnh lịch sự của Shannon Mackey-Bojack, Jesse Edwards Registry của bệnh tim mạch, Nasseff Trung tâm Trung tâm, Vương bệnh viện, trường đại học Minnesota y, St Paul, MN, Mỹ.Hiện tượng 'Tức giận Thrombus'The 'angry thrombus' is an angiographic clinical term that describes a unique pathologic and aggressive thrombus-accumulation, which complicates PCI in thrombus containing lesions.[4] Considered by experienced interventionalists as an ominous sign of impending complication, this type of aggressive clot formation can occur at any stage of coronary or peripheral interventions. Once an 'angry thrombus' is formed it rapidly aggregates at the target lesion and beyond, frequently protruding (proximally and distally) deeply into the treated vessel.[22] Noteworthy, an 'angry thrombus' can easily reach a size of TIMI thrombus grade 3–5. It imposes considerable danger of clot fragmentation followed by downstream embolization and occlusion of smaller arteries. Left untreated, the 'angry thrombus' rapidly causes cessation of antegrade flow, distal embolization and marked decrease in myocardial perfusion. This process frequently leads to AMI accompanied by severe hemodynamic instability. Commonly, the 'angry thrombus' resists the standard pharmacologic regimen, balloon angioplasty and stenting.[23] The correct and best method for the management of this adverse thrombotic process initially requires an accurate assessment of the thrombus location and size. Angiographic identification of a rapid increase in the thrombus volume should be followed by expeditious clot removal. In most cases an aggressive, angry thrombus does not responds readily to aspiration catheters and requires mechanical thrombectomy and enhanced pharmacotherapy to promptly achieve restoration of antegrade flow and myocardial perfusion.[22] Coronary Thrombus Grading SystemsThrombus grading scales are essential tools used for qualification and quantification of the thrombus burden. They provide a platform for clinical assessment and subsequently effect management decisions prior to and during interventions. The widely used TIMI thrombus grading scale was originally created by the TIMI study group investigators.[24] The introduction of this universal classification reflected a growing recognition among cardiologists that the yield of thrombolytic therapy for evolving AMI was defined by different size and burden of intracoronary thrombi. Altogether, the TIMI classification relies on the angiographic assessment of the presence of thrombus and its relative size, utilizing a simple score ranging from grade 0 (no thrombus), to grade 5 (very large thrombus content that completely occludes vessel flow; ).Box 1. The TIMI thrombus scale.•Grade 0: no angiographic evidence of thrombus•Grade 1: angiographic features suggestive