Arterial thrombi

In general, arterial thrombi are platelet-rich ( white clots ) and form at ruptured atherosclerotic plaques, leading to intraluminal occlusion of arteries that can result in end-organ injury (e.g., myocardial infarction, stroke). In contrast, venous thrombi consist mainly of fibrin and red blood cells ( red clots ), and usually form in low-flow veins of the limbs, producing deep vein thrombosis (DVT) the major threat to life results when lower extremity (and, occasionally, upper extremity) venous thrombi embolize via the right heart chambers into the pulmonary arteries, i.e., pulmonary embolism (PE). 

Platelets play a role in each of the mechanisms of normal hemostasis vasoconstriction, formation of the platelet plug, and blood coagulation. However, they are also involved in pathological processes that lead to atherosclerosis and thrombosis (formation of a blood clot within the vascular system). Antiplatelet drugs interfere with platelet function and are used to prevent the development of atherosclerosis and formation of arterial thrombi. 

Arterial thrombi (white thrombi) are formed initially from both platelets and fibrin in medium-sized arteries on the basis of atherosclerosis. These thrombi can lead to symptoms of, among others, myocardial ischemia and myocardial infarction. The treatment is primarily aimed at prevention of thrombus formation with platelet aggregation inhibitors. For the treatment of myocardial infarction thrombolytic agents are used and for secondary prevention both oral anticoagulants and anti-platelet drugs are employed. 

Since arterial emboli formation involves platelet aggregation and leukocyte and erythrocyte inhltration into the fibrin network, the treatment and prophylaxis of arterial thrombi are more difficult. Arterial embolism is treated more successfully with heparin than with the oral anticoagulants. Anticoagulants are useful for prevention of systemic emboli resulting from valvular disease (rheumatic heart disease) and from valve replacement. 

It is used in lysis of suspected occlusive coronary artery thrombi associated with evolving MI in adults. 

A red thrombus can form around a white thrombus as mentioned above or de novo in low-pressure veins, initially by adherence of platelets (as in arteries) but followed promptly by the process of blood coagulation so that the bulk of the thrombus forms a long tail consisting of a fibrin network in which red cells are enmeshed. These tails become detached easily and travel as emboli to the pulmonary arteries. Such emboli often arise from a deep venous thrombosis (DVT)—a thrombus in the veins of the legs or pelvis. Although all thrombi are mixed, the platelet nidus dominates the arterial thrombus and the fibrin tail the venous thrombus. Arterial thrombi cause serious disease by producing local occlusive ischemia venous thrombi, by giving rise to distant embolization. 

Andre R Prasad KS, Denis CY et al, CD40L stabilizes arterial thrombi by a beta 3 integrin-dependent mechanism, Nat Med 2002 8 247-252. 

Mizuno K, Satumora K, Miyamoto A, et al. Angioscopic evaluation of coronary artery thrombi in acute coronary syndromes. N Engl J Med 1992 326 287-291. 

Robbie LA, Young SP, Bennett B, Booth NA (1997) Thrombi formed in a Chandler loop mimic human arterial thrombi in structure and PAI-1 content in distribution. Thromb Haemost 77 510-515... 

Jang IK, Gold HK, Ziskind A A et al. (1989) Differential sensitivity of erythrocyte-rich and platelet-rich arterial thrombi to lysis with recombinant tissue-type plasminogen activator. Circulation 79 920-928... 

It has been shown by Best et al. (1938) that the thrombi formed in the AV-shunt are to a greater part white arterial thrombi. This might be due to the high pressure and shear rate inside the shunts the thrombi tend to be more arterial in character (Chi et al. 1999). 

Cardiovascular diseases are the leading cause of death in the Western world. Basically, atherosclerosis manifests itself in three major organs and thereby leads to severe secondary diseases. Coronary disease results from atherosclerosis of the coronary arteries and culminates in myocardial infarction when vessels are occluded by a thrombus. In the brain, atherosclerosis gives rise to arterial thrombi or ruptures that result in a stroke. Atherosclerosis in the kidney leads to renal failure. Since these diseases significantly lower life expectancy, early recognition and elimination of risk factors (hypertension, diabetes mellitus, hyperlipidemia, and smoking) that promote atherosclerosis are essential. 

Epinephrine Histamine Peripheral arterial thrombi in hyperlipemic rats Coronary spasm damage to endothelial cells in hepatic portal vein Participates in thrombogenesis... 

Thromboses in arteries and veins are slightly different. Venous thrombi form in slow moving blood and contain a lot of fibrin. Arterial thrombi usually occur because of damage to artery walls and contain more platelets than fibrin. Formation of emboli is a risk in either case. 

Platelet adhesion to vessel walls and the subsequent release of adenosine diphosphate (ADP) initiates the formation of the arterial (white) thrombus. The arterial thrombus grows as platelets aggregate. As the thrombus occludes blood flow, it is surrounded by a "red" clot, composed of fibrin, platelets and erythrocytes. Like atherosclerotic plaques, arterial thrombi occlude blood vessels, causing tissue ischemia. 

The tendency to equate lipids with a hypercoagulable state and intravascular coagulation should be undertaken with caution pending further, more convincing evidence. Although platelets are a major component of arterial thrombi, their presence in these lesions is probably related to their role in hemostasis rather than coagulation. 

Group A APS AC-Induced Thrombolysis. The 6 animals in Group A developed occlusive arterial thrombi in 133 12 min. The influence of APSAC alone immediately proximal to the occlusive lesion lysed the thrombus in each of the 6 animals within a mean time of 17 3 min. Despite the efficacy of APSAC in achieving thrombolysis, reocclusion of the carotid artery occured in all animals within an additional 40 5 min. Blood flow velocity throughout the experimental protocol is summarized (Figure 3A). The mean weight of the thrombi removed from the occluded carotid arteries was 62 9 mg. 

Group B APSAC-Induceed Thrombolysis Plus 7E3 F(ab )2 Monoclonal Antibody. The mean time to carotid artery occlusion for the 6 animals in Group B was 108 13 min. The occlusive carotid arterial thrombi in Group B animals treated with APSAC lysed within 26 8 min. After clot lysis was achieved, 7E3 F(ab )2 was administered and the carotid artery remained patent in each of the 6 animals for the remainder of the experimental protocol. Blood flow velocity throughout the experimental protocol is summarized (Figure 3A). The carotid artery thrombi removed at the end of the study had a mean weight of 30 8 mg. 

The present investigations, although limited to the local application of fibrolase, demonstrate that under these conditions the enzyme lyses venous or arterial thrombi rapidly and with no observable systemic or hematologic side effects. In these thrombosis model systems the enzyme, either alone or in combination with antiplatelet therapy, offers a unique, safe, and specific mechanism for clot dissolution and may prove useful as a clinically effective alternative to, or for use in synergistic combination with, presently used thrombolytic agents. 

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