Lecture 5.1 - Thrombosis and Embolism PDF

Thrombosis: ◦Defined as a solidification of blood contents that forms within the vascular system ‣ Solid mass in the lumen of the vessels (occluded lumen) Virchow's Triad: ◦Formed by three factors. You only need two to form a thrombus: ‣ Changes in the intimal surface...

Thrombosis: ◦Defined as a solidification of blood contents that forms within the vascular system ‣ Solid mass in the lumen of the vessels (occluded lumen) Virchow's Triad: ◦Formed by three factors. You only need two to form a thrombus: ‣ Changes in the intimal surface of the vessel ‣ Changes in the pattern of blood flow (sluggish, turbulent blood flow etc) Occurs more in the arterial blood flow in comparison to venous flow ‣ Changes in the blood constituents (e.g. pregnancy as coagulation factors are increased, surgery, smokers, after a burn, inheritance Endothelial damage: ◦This can occur in a number of situations including after myocardial infarction (there is damage to area of endothelium overlying the infarct), secondary to the haemodynamic stress of hypertension, on scarred heart valves, after trauma or surgery, in inflammation and on the surface of atherosclerotic plaques when they break open. ◦As in clotting, when there is endothelial damage, platelets adhere to exposed von Willebrand factor/factor VIII complex. ◦When blood flow is swift, for example in arteries, the platelet thrombi generally don’t grow because the current washes away the platelets, chemical mediators and clotting factors. ◦However if there is also stasis then a thrombus will form. Slow or turbulent flow: ◦Abnormal blood flow gives platelets a better chance to stick to the endothelium and clotting factors a chance to accumulate. ◦Unsurprisingly therefore, thrombosis is more frequent in veins as they have slower flow and the valves produce eddies and pockets of stagnant blood. Blood flow in veins is particularly slow in cardiac failure. It is also slow in patients on bed rest or who are immobilised as the lack of muscular contractions in the calves results in blood stasis. All such patients are predisposed to thrombosis. ◦Slow/turbulent flow also occurs over ulcerated atherosclerotic plaques, within aneurysms, around abnormal heart valves and in the heart where a section of the myocardium isn’t contracting following myocardial infarction. ◦To exacerbate the problem, turbulent flow can itself produce endothelial damage. ◦Abnormal flow also allows thrombi to grow more easily. Hypercoagulability: ◦In pregnancy and after surgery, fractures or burns there are increased circulating levels of fibrinogen and factor VIII meaning that the blood is hypercoagulable. ◦Smoking also results in hypercoagulability as it is known to activate Hageman factor (factor XII). ◦Some cancers produce procoagulant substances. ◦The oral contraceptive pill, particularly older preparations, causes hypercoagulability.  ◦Hypercoagulability is also seen in DIC. Hypercoagulability can be the result of inherited disorders such as factor V Leiden, antithrombin III deficiency, protein C deficiency or protein S deficiency. Thrombus formation: ◦Main components of arterial thrombus: platelets, RBCs. fibrin ◦Main components of venous thrombus: RBCs, fibrin Appearance of thrombi: ◦Arterial: ‣ Pale - as there are more platelets ‣ Lines of Zahn - alternating lines of pink and white/yellow ‣ Lower cell content - disposition of platelets and fibrin ◦Venous: ‣ Soft ‣ Red - due to RBCs ‣ Gelatinous ‣ Higher cell content - due to RBCs and fibrin Outcome of thrombosis: ◦Lysis - the thrombus is dissolved ◦Propagation - the thrombus grows ◦Organisation - the thrombus undergoes fibrous repair and forms a fibrous scar on the wall of the vessel ◦Recanalisation - happens in an occluding thrombus, new channels lined with endothelium run through the occlusion and restore blood flow, although the new channels may have significantly smaller capacity than the original vessel ◦Embolisation - a part of the thrombus breaks off and embolises. This is called thromboembolism. Thrombi that form in the large veins of the lower limbs such as the femoral, iliac and popliteal veins are particularly dangerous sources of thromboemboli. Lysis:  ◦When the thrombus is relatively small ◦Dependent upon fibrinolytic activity (e.g. plasmin) Propagation: ◦Progressive spread of thrombosis ‣ Original thrombus is a risk factor of propagation Organisation: ◦Ingrowth of fibroblasts and small capillaries (similar to granulation tissue) ◦Lumen remains obstructed ◦Scar formation takes place (thrombus changes to scar tissue) Recanalisation: ◦Occurs by the ingrowth of new small vessels ◦The new vessels join up to restore blood flow, at least partially Embolisation: ◦Caused by fragmentation of the thrombus ◦Results in infarction at a distant site ◦Embolisation doesn't happen in veins as the diameter of veins increases as you get closer to the heart, so embolism can still travel through Thrombo-emboli: ◦From systemic veins - pass to the lungs to form pulmonary emboli ◦From the heart pass via the aorta to renal, mesenteric and other arteries ◦From atheromatous carotid arteries pass to the brain to cause stroke ◦From atheromatous abdominal aorta pass to arteries of the legs Effects of thrombosis:  ◦Thrombus could be due to atherosclerosis, infarction, infection of the heart etc. ◦The most common clinical effects of thrombosis include: ‣ Occlusion of an artery at the site of the thrombus resulting in ischaemia and infarction, e.g. myocardial infarction. ‣ Embolisation of part of the thrombus resulting in occlusion of an artery distant to the site of the thrombus, e.g. pulmonary embolism, cerebrovascular accident. ‣ Congestion and oedema in the venous bed resulting in pain and sometimes skin ulceration. ‣ Repeated miscarriages due to thrombosis of the uteroplacental vasculature which is often seen in inherited thrombophilias. Cerebral infarct: Outcome of thrombosis: Effects of thrombosis: ◦Arterial: ‣ Ischaemia ‣ Infarction ‣ Depends on site and collateral circulation ◦Venous: ‣ Congestion - blood doesn't go back to the heart, so accumulation of fluid takes place (oedema) ‣ Oedema  ‣ Skin ulceration Venous thrombosis: Embolism: ◦An embolus is a mass (can be solid liquid or gas) of material in the vascular system able to become lodged within a vessel and block its lumen ◦Embolism is the impaction of an embolus. A good definition for embolism would be ‘Sudden blocking of an artery by a thrombus or foreign material which has been brought to its site of lodgement by the blood current’. ◦Most emboli originate from thrombi - due to fragmentation of the thrombus ◦The most common type is pulmonary embolism from lower limb deep vein thrombosis ◦Thromboemboli are emboli that arise from thrombi. They are far and away the most common type of emboli and when they occur are often multiple. ◦Emboli can also be composed of body fat, bone marrow, material from atheromatous plaques, tumour fragments, parasites, bubbles of air or other gases, debris injected intravenously, amniotic fluid, medical equipment or bits of brain or liver after trauma. ◦In veins blood flow is from smaller to larger vessels, hence embolization cannot occur in veins. Objects carried by the blood in veins will therefore go through the right heart and embolise in the pulmonary arteries. ◦In arteries blood flow is from large to small arteries so that objects carried by the blood in large arteries will become impacted into smaller arteries. Emboli from the left heart or aorta end up anywhere in the systemic circulation but especially in the lower limbs. Deep vein thrombosis: ◦Predisposing factors: ‣ Immobility/bed rest ‣ Post-operative ‣ Pregnancy and postpartum ‣ Oral contraceptives ‣ Severe burns ‣ Cardiac failure ‣ Cancer Pulmonary embolism: ◦Massive PE > 60% reduction in blood flow - rapidly fatal ◦Major PE - medium sized vessels blocked. Patients feel chest pain with shortness of breath +/- cough and blood-stained sputum (hemoptysis) ◦Minor PE - small peripheral pulmonary arteries blocked. Asymptomatic or minimal shortness of breath ‣ Can lead to right-sided heart failure ◦Recurrent minor PEs lead to pulmonary hypertension  Embolism: ◦Embolus derived from a lower-extremity deep venous thrombus lodged in a pulmonary artery branch. Saddle embolism: Embolism: ◦Other types: ‣ Paradoxical emboli Starts in venous system but damage takes place in arterial circulation Embolism can be pushed from right atria to left atria if defects such as patent foramen ovale or interventricular septum defect are present ‣ Emboli from atheroma - due to atherosclerosis Can travel somewhere else It can be released into the blood when a plaque breaks open. This can happen spontaneously and also during surgery or catheterisation for coronary artery disease. Such emboli often affect the intestine and present with abdominal pain. Transient ischaemic attacks (TIAs) are episodes of neurological dysfunction that appear suddenly, last minutes to hours and then disappear. They are the result of microscopic emboli, usually atheroemboli, to the brain. The atheroembolus usually comes from the carotid arteries. Sometimes they are the result of thromboemboli that arise in the left heart. As the emboli are very small they break up quickly before any lasting damage is done and this is why the neurological symptoms disappear after a short time. ‣ Fat and bone marrow emboli  These are usually a complication of bone fractures but fat emboli can also occur after liposuction. When a bone is fractured the bone marrow fat cells that are injured break up and release oil droplets. These coalesce over a period of a few days and are then sucked into gaping venules that have been torn by the fracture. Symptoms of fat embolism (respiratory distress and neurological symptoms) are therefore seen one to three days after the fracture. They are said to occur in 5- 10% of patients with pelvic or long bone fractures and mortality is 10-15%. Respiratory symptoms are the result of emboli that lodge in the lungs. Some droplets however will pass through the lungs in a similar way to small thromboemboli and into organs such as the brain, kidneys and skin where they will cause symptoms such as agitation, coma, renal failure and a petechial rash. ‣ Amniotic fluid - mother can present with shortness of breath This is seen as a complication of labour and caesarean section when amniotic fluid enters the maternal circulation through a tear in the amniotic membranes. It occurs in approximately one in 50,000 deliveries and has a mortality rate of 20- 40%. It causes sudden respiratory distress, hypotension, seizures, loss of consciousness and disseminated intravascular coagulation (as amniotic fluid contains prothrombotic substances). Microscopic emboli of foetal origin (e.g., epithelial squames, lanugo hair, meconium (all of which can be present in amniotic fluid)) are found in the lungs ‣ Gas embolism There is negative pressure in the veins of the chest and head during inspiration in the upright position. These veins can draw in air after, for example, trauma of the neck and chest. A fatal amount of air is approximately 100 mls. The air is transported to the right heart where bubbles gather as a frothy mass that stops the circulation. Air embolism can also occur during labour as air can enter the uterus and be forced into open veins during uterine contraction. Thromboembolic disease: ◦Prevention and treatment: ‣ General prophylaxis (increase motility) This can be achieved either by preventing venous stasis or by preventing hypercoagulability. To prevent stasis patients should be encouraged to mobilise early after an operation or illness. During and after an operation legs can be elevated and measures to increase venous return such as compression stockings, calf muscle stimulation, and passive calf muscle exercises can be employed. Anticoagulants are used to prevent hypercoagulability. ‣ Aspirin Aspirin is antithrombogenic. It irreversibly acetylates an enzyme of prostaglandin synthesis (cyclooxygenase) and this means that platelets can’t produce thromboxane A2 which is a powerful platelet aggregator. The formation of a haemostatic plug is inhibited in patients taking aspirin and the bleeding time is prolonged. It is used in certain patients to reduce the risk of myocardial infarction and stroke. It has also been recommended as a prophylactic against deep vein thrombosis in patients who are taking long haul flights. ‣ Heparin Low molecular weight heparin is used as prophylaxis against thrombosis and also to treat thrombosis. It is given subcutaneously or intravenously. It forms irreversible complexes with antithrombin III resulting in its activation. ‣ Warfarin - affects vitamin K  Warfarin, like heparin, is used as prophylaxis against thrombosis and also to treat thrombosis. It is an oral medication which interferes with vitamin K metabolism. The dosage required is titrated to the patients PT test results, specifically the INR results (INR stands for international normalised ratio which is the ratio of the patient’s PT to a normal control). ‣ Filters- umbrella that stops fragment travelling to pulmonary circulation (surgical procedure) Pulmonary emboli can be prevented by putting an umbrella-shaped filter in the inferior vena cava.