Flashcards in 5. Thrombosis and embolism Deck (22)
What is thrombosis and when does it occur?
Process of formation of a thrombus.
Occurs when normal haemostatic mechanisms are turned on inappropriately.
What is a thrombus?
Solid mass formed from the constituents of blood within the heart or vessels during life.
Name the 3 causative factors for thrombosis.
1. changes in vascular wall (endothelial damage)
2. changes in blood flow (slow or turbulent flow)
3. changes in the blood (hypercoagulability)
Which of Virchow's factors are more likely to cause arterial, venous and cardiac thrombi?
Arterial and cardiac thrombi usually occur at: sites of endothelial injury or turbulence.
Venous thrombi usually occur at: sites of stasis.
Why is there an increased risk of thrombi in the lower limbs in pregnancy?
1. Stasis due to pressure on large veins of pelvis by uterus
2. Blood is hypercoaguable
Why does endothelial damage lead to thrombosis?
i) Endothelial damage causes platelets to adhere to exposed von Willebrand factor/factor VIII complex.
ii) If there is also stasis, thrombus will form (when blood flow is swift, e.g. in arteries, platelet thrombi generally don't grow because current washes away platelets, chemical mediators and clotting factors)
Give examples of why endothelial damage might occur.
1. after MI (damage to area of endothelium overlying infarct)
2. secondary to haemodynamic stress of hypertension
3. scarred heart valves
4. after trauma or surgery
6. on surface of atherosclerotic plaques when they break open
Why does slow/turbulent blood flow lead to thrombosis?
1. Abnormal blood flow gives platelets a better chance to stick to endothelium, and clotting factors a chance to accumulate - thrombus can grow more easily.
2. Turbulent flow can itself produce endothelial damage - exacerbates problem.
Why is thrombosis more frequent in veins?
1. Slower flow
2. Valves produce eddies and pockets of stagnant blood
Give examples of why slow/turbulent blood flow might occur.
Slow blood flow:
1. cardiac failure
2. bed rest/immobilisation due to lack of muscular contractions in calves - causes stasis
Slow or turbulent flow:
3. ulcerated atherosclerotic plaques
4. within aneurysms
5. around abnormal heart valves
6. in heart where a section of myocardium isn't contracting following MI
Give examples of why blood hypercoagulability might occur.
1. pregnancy, post-surgery, fractures or burns: cause increased circulating levels of fibrinogen and factor VIII
2. smoking: activates factor XII (Hageman factor)
3. some cancers: produce procoagulant substances
4. oral contraceptive pill (esp. older preparations)
6. Inherited disorders such as factor V Leiden, antithrombin III deficiency, protein C or S deficiency
Explain the process of initial platelet aggregation in thrombosis.
i) Platelets are the smallest formed elements in the blood... so are more concentrated along the endothelium... so are more likely to catch in an eddy behind a valve.
ii) Form an aggregate and settle on vessel wall, esp. if there is endothelial injury or blood flow is slow.
iii) Further platelets join aggregate.
What happens after initial platelet aggregation in thrombosis?
i) Fibrinogen binds platelets together (as in haemostasis) and fibrin grows out of platelet layer.
ii) Fibrin traps RBCs - white layer of platelets is covered by red layer of fibrin and RBCs.
iii) Surface of red layer is thrombogenic so platelets stick to exposed fibrin.
iv) 2nd white layer of platelet forms and process continues.
What are 'Lines of Zahn'?
Laminations of a thrombus visible to the naked eye.
Are more obvious in arterial thrombi as opposed to venous thrombi as blood flows over the surface of the forming thombus in arteries.
Is pain associated with thrombus formation?
Not always, though common when thrombus forms in superficial veins = phrombophlebitis (has associated inflammation in vein wall)
What is the difference between parietal and occlusive thrombi? Arterial thrombi are more likely to be of which type?
Parietal thrombus = attached to vessel wall and restricts lumen. Arterial thrombi rend to remain parietal.
Occlusive thrombus = fill and obstruct vessel lumen
When are occlusive arterial thrombi more likely to occur?
Over an atherosclerotic plaque that has cracked open.
Can be fatal in coronary arteries.
What is a vegetation? Where do these usually form?
Thrombus on a cardiac valve - can be 2-3cm long and easily embolise.
Usually form on valves of left heart as are exposed to greater pressures and therefore microtraumas which exposes the thrombogenic subendothelial tissue.
Can become infected - esp. in IV drug users.
What are the 5 main outcomes of thrombus formation?
1. resolution - thrombus dissolves
2. propagation - thrombus grows
3. organisation - thrombus undergoes fibrous repair and forms a fibrous scar on the wall of the vessel
4. recanalisation (of an occluding thrombus) - new channels lined with endothelium run through the occlusion and restore blood flow (although new channels may have significantly smaller capacity than the original vessel)
5. embolisation - part of thrombus breaks off and embolises (= thromboembolism)
Which thrombi are particularly dangerous sources of thromboemboli?
Thrombi that form in the large veins of the lower limbs, e.g. femoral, iliac and popliteal veins.
What are the most common clinical effects of thrombosis?
1. occlusion of an artery at the site of thrombus... ischaemia and infarction (e.g. MI)
2. Embolisation of part of thrombus... occlusion of an artery distant to site of thrombus (e.g. pulmonary embolism, cerebrovascular accident)
3. Congestion and oedema in venous bed... pain and sometimes skin ulceration
4. Repeated miscarriages due to thrombosis of the uteroplacental vasculature which is often seen in inherited thrombophilias.