Thrombi and Emboli

Plasmin activity is eliminated from the blood by autocatalytic digestion, inhibition by antiplasmin agents, and elimination in the urine. 

This description of the plasminogen-plasmin systems illustrates how little is known of this basic physiological system no substrate, product, activator, or inhibitors have been characterized. The mechanisms triggering activation of plasminogen and inhibition of plasmin are unknown. Yet, the elucidation of some of the steps involved in converting plasminogen to plas-minhashelpedourunderstandingofhyperplasminemia. 

Hyperproteolytic activity of plasma may result from excessive amounts of plasminogen activator, deficiency in plasmin inhibitors, or appearance in plasma of proteolytic enzymes different from plasmin. Severe anoxia or shock releases large amounts of activators, and the rate of conversion of plasminogen to plasmin exceeds that of inhibition of plasmin activity. Patients with severe liver impairment (liver cirrhosis) may become unable to clear the activator from the blood, but in liver disease the levels of plasmin inhibitor may be low. 

Some pathological conditions have been suggested to result from inhibition of fibrinolysis. Lieberman 

Appearance in plasma of proteolytic enzymes other than plasmin-e.g., urokinase 

---

Thrombus versus embolus A clot that adheres to a vessel wall is called a thrombus, whereas an intravascular clot that floats within the blood is termed an embolus. Thus, a detached thrombus becomes an embolus. Both thrombi and emboli are dangerous, because they may occlude blood vessels and deprive tissues of oxygen and nutrients. Arterial thrombosis most often involves medium-sized vessels rendered thrombogenic by surface lesions of endothelial cells caused by atherosclerosis. In contrast, venous thrombosis is triggered by blood stasis or inappropriate activation of the coagulation cascade, often as a result of a defect in the normal defense hemostatic mechanisms. 

Carrie D, Caranobe C, Saivin S et al. (1994) Pharmacokinetic and antithrombotic properties of two pentasaccharides with high affinity to antithrombin III in the rabbit comparison with CY 216. Blood 84(8) 2571-2577 Dewanjee MK, Wu S, Kapadvanjwala M et al. (1996) Reduction of platelet thrombi and emboli by L-arginine infusion during cardiopulmonary bypass in a pig model. J Thromb Thrombolysis 3 339-356... 

Q6 A thrombus is a blood clot which is fixed to the blood vessel wall. When it detaches and is carried in the blood, it is known as an embolus. Both thrombi and emboli can block blood vessels and deprive tissues of oxygen. In arteries blood clots usually form because the inner surface has been altered by deposition of atheroma. In contrast venous thrombosis results from slow or stagnant blood flow in veins, or defects in mechanisms which normally oppose inappropriate coagulation. Three major risk factors for pulmonary embolism are (i) venous stasis, (ii) hypercoagulability ofblood and (iii) injury to vascular endothelium following trauma or plaque rupture. 

Fibrinolytics (thrombolytics) can remove established thrombi and emboli. Inhibitors of the fibrinolytic system (antifibrinolytics) can be of value in certain haemorrhagic states notably those characterised by excessive fibrinolysis. 

Knight, L.C. (2001) Radiolabeled peptide ligands for imaging thrombi and emboli,... 

A pathological situation arises when thrombi and emboli develop, either as causative factors in such conditions as strokes or in other thromboembolic disorders following a cardiovascular ischemia (e.g., a myocardial infarction, MI). These, then, continue to threaten the patient s life. 

Clinical effects produced by thrombi and emboli are (1) no serious effects, the silent thrombus or embolus (2) oedema of a limb, venous thrombus and perivenous lymphangitis (3) post-thrombotic ulceration (4) gangrene of a limb (thrombosis of main artery or embolus from heart or aorta) (5) gangrene of bowel (thrombosis of mesenteric artery or vein, arterial embolism) ... 

Vascular Factors in Blood Coagulation 413 Fibrinolysis 413 Thrombi and Emboli 415... 

The therapeutic effect achieved lysis of thrombi or emboli occurs and the catheter or cannula is patent. 

Venous (red) thrombi develop in areas of slow blood flow (e.g., leg veins of a bedridden patient). The clot forms rapidly and lacks the organization of the arterial thrombus. Venous occlusion occurs, but is not the primary damage caused by venous thrombi. More worrisome is the tendency of small pieces (emboli) to detach from venous thrombi and travel to pulmonary arteries. The emboh wedge into pulmonary arteries, prohibiting deoxygenated blood from entering the portion of the limg served by the embolized artery. 

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. 

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. 

Q13 Arterial emboli, which can block blood vessels and cause ischaemia or infarction in the tissues they affect, tend to originate in the left heart and are associated with valvular disease and dysrhythmias. Mitral stenosis is associated with abnormal atrial rhythm, particularly atrial fibrillation. Fibrillation and other rhythm abnormalities in the atria favour blood coagulation, resulting in production of thromboemboli which can move to distant parts of the circulation, such as the cerebral circulation. Thrombi could also form on surfaces of valves distorted by calcification and other abnormalities. In view of the risks of thromboembolism, it is usual to provide anticoagulant therapy to patients with mitral valve problems and atrial fibrillation. 

Autopsy examples have established that paradoxical embolism can occur from venous thrombi through the right to the left side of the heart. Emboli may pass through a patent foramen ovale, which is found in approximately one-quarter of healthy people, an atrial septal defect or a ventriculoseptal defect (Gautier et al. 1991 Jeanrenaud and Kappenberger 1991 Cabanes et al. 1993). There is an increased incidence of patent foramen ovale in... 

Acute myocardial infarction. Anticoagulation with heparin is used to reduce the risk of venous thromboembolism, and the risk and size of emboli from mural thrombi following acute myocardial infarction. 

Other uses of TEE include identification of cardiac thrombus, especially thrombi in the left atrium, and assessment of atrial dilation. After transient ischemic attacks or cerebrovascular accidents, TEE may enable identification of the site of cardiac emboli by providing excellent images of likely sources of such, namely, ventricular or atrial thrombus, valvular vegetation, cardiac shunts, cardiac tumors, or atrial and ventricular septal defects. In a study of almost 1500 patients with cerebral ischemia or nonvalvular atrial fibrillation, atrial thrombi were seen in 183 patients when evaluated by TEE versus only 2 patients using TTE. TEE can be used for intraoperative cardiac imaging to ascertain development of ischemia. 

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. 

The degree and level of occlusion have been shown to be important factors in planning acute stroke therapy. In early studies, intravenous rt-PA for clot lysis was more likely to be effective in secondary and tertiary MCA branch occlusions than in larger, more proximal occlusions [6, 86]. In another stndy nsing CTA, there was little benefit from intravenons rt-PA when there was poor collateralization, autolyzed thrombi, or proximal top of carotid saddle emboli [87]. In still other studies, top of ICA carotid terminus occlusion was demonstrated to be a better predictor of fatal outcome than an admission unenhanced CT showing greater than one-third MCA territory hypoden-sity [88, 89]. 

Fragments of the thrombi may become detached, be released in the general circulation, and finally get caught in vessels distant from the thrombotic vessel. As we have seen, these ectopic vascular plugs are called emboli. Venous emboli originate from thrombi that developed in the peripheral veins. Emboli that plug the major pulmonary arteries are often responsible for sudden death. When emboli are found in the peripheral arteries, they usually originate from thrombi in the heart or in an aneurysmal sac. The steps involved with formation of blood clots or thrombi are summarized in Fig. 7-8. 

Other postmortem findings included tricuspid valvular lesions in all four patients who had been treated with superior vena cava catheters and developed septic thrombi. These lesions consisted of tricuspid endocarditis in three instances and one case with a septic tricuspid infarct. All patients had radiologic evidence of catheter in the heart at some time during their nutritional therapy. There were three patients with multiple small pulmonary emboli, but no instance of massive pulmonary embolus was noted. 

---