Non-bacterial thrombotic endocarditis pathophysiology
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non-bacterial thrombotic endocarditis |
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Differentiating non-bacterial thrombotic endocarditis from other Diseases |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Homa Najafi, M.D.[2]
Overview
The exact pathogenesis of [disease name] is not fully understood.
OR
It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
OR
[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
OR
Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
OR
[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
OR
The progression to [disease name] usually involves the [molecular pathway].
OR
The pathophysiology of [disease/malignancy] depends on the histological subtype.
Pathophysiology
Physiology
The normal physiology of [name of process] can be understood as follows:
Pathogenesis
- The exact pathogenesis of [disease name] is not completely understood.
OR
- It is understood that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
- [Pathogen name] is usually transmitted via the [transmission route] route to the human host.
- Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
- [Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
- The progression to [disease name] usually involves the [molecular pathway].
- The pathophysiology of [disease/malignancy] depends on the histological subtype.
Genetics
[Disease name] is transmitted in [mode of genetic transmission] pattern.
OR
Genes involved in the pathogenesis of [disease name] include:
- [Gene1]
- [Gene2]
- [Gene3]
OR
The development of [disease name] is the result of multiple genetic mutations such as:
- [Mutation 1]
- [Mutation 2]
- [Mutation 3]
Associated Conditions
Conditions associated with [disease name] include:
- [Condition 1]
- [Condition 2]
- [Condition 3]
Gross Pathology
On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
Microscopic Pathology
On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
The instigating factor causing NBTE is not entirely known, but involves endothelial cell injury in the setting of a hypercoagulable state. The acute injury results in platelet deposition and migration of inflammatory mononuclear cells to form thrombi interwoven with fibrin and immune complexes.6 These cardiac lesions are always sterile, which is an important distinction from infective endocarditis. NBTE vegetations commonly involve the mitral and aortic valves; these lesions can affect both undamaged and damaged cardiac valves, as well as the chordae tendineae or the endocardium. Compared to the lesions in infective endocarditis, NBTE vegetations are more friable and prone to systemic embolization.7 NBTE is most notably associated with malignancy, antiphospholipid syndrome and SLE.8,9 A large echocardiographic study revealed NBTE to be found in 19% of disseminated adenocarcinomas.10 In malignancy, macrophages interact with malignant cells to release cytokines (tumor necrosis factor, interleukin-1 and 6), which damage endothelium and promote platelet deposition, ultimately forming friable thrombi. Macrophages also interact with tumor cells to over-activate the coagulation cascade, hence worsening the hypercoagulable state.1 NBTE tends to cluster in areas of high turbulence around heart valves.8 Primary antiphospholipid syndrome is characterized by the formation of autoantibodies directed against phospholipids in endothelial cell membranes.9 These autoantibodies damage the endothelium, which similarly promote the platelet and thrombi deposition seen in NBTE.However, the presence of antiphospholipid antibodies is not required, as NBTE has been found to occur in SLE patients without having the antiphospholipid syndrome.5 In SLE, chronic deposition of immunoglobulins and complement factors onto cardiac valves form Libman-Sacks vegetations.11,12 The formation of these verrucous vegetations can cause eventual valve fibrosis and dysfunction. Valvular abnormalities in SLE patients include valvular thickening, vegetations, valvular regurgitation and stenosis.13 Many studies have characterized the various stages of Libman-Sacks endocarditis in chronic patients. The 3 stages include active, active with healing, and healed lesions. Healed lesions are seen as fibrous plaques with scarring, thickening and deformity of the valve.14-16 The advent of steroid therapy has prolonged the lifespan of lupus patients as well as the chronicity of Libman-Sacks endocarditis. Steroid therapy has been linked to increased amounts of valvular fibrosis, scarring and dysfunction.17-19
The term "nonbacterial thrombotic endocarditis" (NBTE, marantic endocarditis, Libman-Sacks endocarditis, verrucous endocarditis) is a form of noninfectious endocarditis, that is characterized by the deposition of sterile platelet thrombi on heart valves (mostly aortic and mitral). NBTE commonly affects undamaged valves although some reports suggest NBTE can occur in patients with valvular pathology [6,8,13]. It is a separate entity to culture-negative endocarditis which is due to infectious etiologies that are not readily identified. (See "Culture-negative endocarditis: Epidemiology, microbiology, and diagnosis".)
NBTE is associated with a number of conditions, of which advanced malignancy is the most common (80 percent of cases) [1,3,7,8,14-17] followed by systemic lupus erythematosus. Less common etiologies include inflammatory conditions such as antiphospholipid syndrome, rheumatoid arthritis, sepsis, and burns.
The initiating factor in the pathogenesis of NBTE is unknown, but endothelial injury in the setting of a hypercoagulable state is thought to be critical for the development of NBTE. Endothelial damage caused by circulating cytokines, such as tumor necrosis factor or interleukin-1, may trigger platelet deposition, particularly in the presence of an activated coagulation system (eg, disseminated intravascular coagulation, malignancy, antiphospholipid syndrome) to result in local deposition of platelets and inflammatory molecules. (See "Non-coronary cardiac manifestations of systemic lupus erythematosus in adults".)
The vegetations in NBTE consist of thrombi interwoven with strands of fibrin, immune complexes and mononuclear cells ("white thrombus") [6]. Vegetations vary in size from microscopic to large and exuberant. When thrombi are large, the term verrucous endocarditis is used (also known as Libman-Sacks endocarditis) (picture 1).
Compared to vegetations in infective endocarditis, vegetations in NBTE are easily dislodged since there is little inflammatory reaction at the site of attachment. Thus, in NBTE there is a greater tendency for vegetations to embolize and cause extensive infarction. This was best illustrated in a six-year study of 76 patients with systemic lupus erythematosus (SLE) where the presence of vegetations was an independent risk factor for the development of neuropsychiatric SLE (odds ratio 13.4) [18]. There were three times more cerebral microemboli events per hour and a higher brain lesion load in patients with vegetations than those without vegetations [18].