Thrombi on heart valves are called vegetations. Bacterial or fungal bloodborne infections can cause valve damage, leading to the development of large thrombotic masses (infective endocarditis) (Chapter 11). Sterile vegetations also can develop on noninfected valves in hypercoagulable states—the lesions of so-called “nonbacterial thrombotic endocarditis” (Chapter 11). Less commonly, sterile, verrucous endocarditis (Libman- Sacks endocarditis) can occur in the setting of systemic lupus erythematosus (Chapter 5). #251 в контекст | | |
Fig. 4.13 Mural thrombi. (A) Thrombus in the left and right ventricular apices, overlying white fibrous scar. (B) Laminated thrombus in a dilated abdominal aortic aneurysm. Numerous friable mural thrombi are also super- imposed on advanced atherosclerotic lesions of the more proximal aorta (left side of photograph). #252 в контекст | | |
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If a patient survives an initial thrombotic event, during the #254 в контекст | | |
ensuing days to weeks the thrombus evolves through some combination of the following four processes: #255 в контекст | | |
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Propagation. The thrombus enlarges through the accre- tion of additional platelets and fibrin, increasing the odds of vascular occlusion or embolization. #257 в контекст | | |
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Embolization. Part or all of the thrombus is dislodged and transported elsewhere in the vasculature. #259 в контекст | | |
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Dissolution. If a thrombus is newly formed, activation of fibrinolytic factors may lead to its rapid shrinkage and complete dissolution. With older thrombi, extensive fibrin polymerization renders the thrombus substantially more resistant to plasmin-induced proteolysis, and lysis is ineffectual. This acquisition of resistance to lysis has clinical significance, as therapeutic administration of fibrinolytic agents (e.g., t-PA in the setting of acute coro- nary thrombosis) generally is not effective unless admin- istered within a few hours of thrombus formation. #261 в контекст | | |
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Organization and recanalization. Older thrombi become organized by the ingrowth of endothelial cells, smooth muscle cells, and fibroblasts (Fig. 4.14). In time, capillary channels are formed that—to a limited extent—create conduits along the length of the thrombus, thereby rees- tablishing the continuity of the original lumen. Further recanalization can sometimes convert a thrombus into a vascularized mass of connective tissue that is eventually incorporated into the wall of the remodeled vessel. Occasionally, instead of organizing, the center of a thrombus undergoes enzymatic digestion, presumably because of the release of lysosomal enzymes from entrapped leukocytes. If bacterial seeding occurs, the contents of degraded thrombi serve as an ideal culture medium, and the resulting infection may weaken the vessel wall, leading to the formation of a mycotic aneu- rysm (Chapter 10). #263 в контекст | | |
Fig. 4.14 An organized thrombus. Low-power view of a thrombosed artery stained for elastic tissue. The original lumen is delineated by the inter- nal elastic lamina (arrows) and is completely filled with organized thrombus. #264 в контекст | | |
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Thrombi are significant because they cause obstruction of #266 в контекст | | |
arteries and veins and may give rise to emboli. The effect that is of the greatest clinical importance depends on the site of thrombosis. Thus, although venous thrombi can cause congestion and edema in vascular beds distal to an obstruc- tion, they are most worrisome because of their potential to embolize to the lungs and cause death. Conversely, whereas arterial thrombi can embolize and cause tissue infarction, their tendency to obstruct vessels (e.g., in coronary and cerebral vessels) is considerably more important. #267 в контекст | | |
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Most venous thrombi occur in the superficial or the deep #269 в контекст | | |
veins of the leg. Superficial venous thrombi usually arise in the saphenous system, particularly in the setting of vari- cosities; these rarely embolize but they can be painful and can cause local congestion and swelling from impaired venous outflow, predisposing the overlying skin to the development of infections and varicose ulcers. Deep venous thromboses (DVTs) in the larger leg veins at or above the knee joint (e.g., popliteal, femoral, and iliac veins) are more serious because they are prone to embolize. Although such DVTs may cause local pain and edema, collateral channels often circumvent the venous obstruc- tion. Consequently, DVTs are entirely asymptomatic in approximately 50% of patients and are recognized only after they have embolized to the lungs. #270 в контекст | | |
Lower-extremity DVTs are associated with stasis and hypercoagulable states, as described earlier (Table 4.2). Thus, common predisposing factors include congestive heart failure, bed rest, and immobilization; the latter two factors reduce the milking action of leg muscles and thus slow venous return. Trauma, surgery, and burns not only immobilize a patient but also are associated with vascular injury, procoagulant release, increased hepatic synthesis of coagulation factors, and reduced t-PA production. Many factors contribute to the thrombotic diathesis of pregnancy; in addition to the potential for amniotic fluid infusion into the circulation at the time of delivery, pressure produced by the enlarging fetus and uterus can produce stasis in the veins of the legs, and late pregnancy and the postpartum period are associated with hypercoagulability. Tumor- associated procoagulant release is largely responsible for the increased risk of thromboembolic phenomena seen in disseminated cancers. These are sometimes referred to as migratory thrombophlebitis, because of the tendency to involve several different venous beds transiently, or as Trousseau syndrome, for the physician who both described the disorder and suffered from it. Regardless of the specific clinical setting, the risk of DVT is increased in persons older than 50 years. #271 в контекст | | |
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Atherosclerosis is a major cause of arterial thromboses #273 в контекст | | |
because it is associated with the loss of endothelial integ- rity and with abnormal blood flow (Fig. 4.13B). Myocardial infarction can predispose to cardiac mural thrombi by causing dyskinetic myocardial contraction and endocar- dial injury (Fig. 4.13A), and rheumatic heart disease may engender atrial mural thrombi by causing atrial dilation and fibrillation. Both cardiac and aortic mural thrombi are prone to embolization. Although any tissue can be affected, the brain, kidneys, and spleen are particularly likely targets because of their rich blood supply. #274 в контекст | | |
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Thrombus development is usually related to one or more components of Virchow’s triad: #277 в контекст | | |
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endothelial injury (e.g., by toxins, hypertension, inflammation, or metabolic products) #279 в контекст | | |
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abnormal blood flow, stasis, or turbulence (e.g., resulting from aneurysms, atherosclerotic plaque) #281 в контекст | | |
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hypercoagulability: either primary (e.g., factor V Leiden, increased prothrombin synthesis, anti-thrombin III deficiency) or secondary (e.g., bed rest, tissue damage, malignancy) #283 в контекст | | |
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Thrombi may propagate, resolve, become organized, or embolize. #285 в контекст | | |
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Thrombosis causes tissue injury by local vascular occlusion or by distal embolization. #287 в контекст | | |
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DIC is widespread thrombosis within the microcirculation that may be of sudden or insidious onset. It may be seen in disorders ranging from obstetric complications to advanced malignancy. To complicate matters, the widespread micro- vascular thrombosis consumes platelets and coagulation proteins (hence the synonym consumptive coagulopathy), and at the same time, fibrinolytic mechanisms are activated. #289 в контекст | | |
The net result is that excessive clotting and bleeding may #290 в контекст | | |
co-exist in the same patient. It is discussed in greater detail along with other bleeding diatheses in Chapter 12. #291 в контекст | | |
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An embolus is a detached intravascular solid, liquid, or gaseous mass that is carried by the blood from its point of origin to a distant site, where it often causes tissue dysfunction or infarction. The vast majority of emboli derive from a dislodged thrombus—hence the term throm- boembolism. Less commonly, emboli are composed of fat droplets, bubbles of air or nitrogen, atherosclerotic debris (cholesterol emboli), tumor fragments, bits of bone marrow, or amniotic fluid. Inevitably, emboli lodge in vessels too small to permit further passage, resulting in partial or com- plete vascular occlusion; depending on the site of origin, emboli can arrest anywhere in the vascular tree. The primary consequence of systemic embolization is ischemic necrosis (infarction) of downstream tissues, whereas embo- lization in the pulmonary circulation leads to hypoxia, hypotension, and right-sided heart failure. #293 в контекст | | |
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Pulmonary emboli originate from deep venous throm- boses and are responsible for the most common form of thromboembolic disease. The incidence of pulmonary embolism (PE) is 2 to 4 per 1000 hospitalized patients. Although the rate of fatal PE has declined considerably since the early 1990s, PE still causes about 100,000 deaths per year in the United States. In more than 95% of cases, venous emboli originate from thrombi within deep leg veins proximal to the popliteal fossa; embolization from lower leg thrombi is uncommon. #295 в контекст | | |
Fragmented thrombi from DVTs are carried through progressively larger channels and usually pass through the right side of the heart before arresting in the pulmonary vasculature. Depending on size, a PE can occlude the main pulmonary artery, lodge at the bifurcation of the right and left pulmonary arteries (saddle embolus), or pass into the smaller, branching arterioles (Fig. 4.15). Frequently, mul- tiple emboli occur, either sequentially or as a shower of smaller emboli from a single large thrombus; a patient who has had one pulmonary embolus is at increased risk for having more. Rarely, an embolus passes through an atrial or ventricular defect and enters the systemic circulation (paradoxical embolism). A more complete discussion of PE is found in Chapter 13; the major clinical and pathologic features are the following: #296 в контекст | | |
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Most pulmonary emboli (60%–80%) are small and clini- cally silent. With time, they undergo organization and become incorporated into the vascular wall; in some cases, organization of thromboemboli leaves behind bridging fibrous webs. #298 в контекст | | |
At the other end of the spectrum, a large embolus that blocks a major pulmonary artery can cause sudden death. #299 в контекст | | |
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