Thrombosis, Embolism, Ischaemia and Infarction Flashcards
Generally, what elements does normal haemostasis involve?
- Platelets
- Thrombin: protease enzyme
- Fibrin: fibrous protein
Explain some general concepts in coagulation cascade.
- A big and complex cascade of plasma proteins
- Triggered by Tissue Factor
- End products include Thrombin and Fibrin
- Thrombin:
- activates fibrin from fibrinogen
- also activates platelets, inflammation, healing etc.
- Fibrin:
- sticks to things
- Coagulation has brakes - like inflammation
Normal endothelium
- doesn’t bind or activate platelets or clotting factors
- produces Thrombomodulin, Protein C and Protein S (to change Thrombin from activator to inhibitor)
Fibrolysis
- Tissue Plasminogen Activator (tPA) (binds to Fibrin and activates Plasmin; Plasmin breaks down Fibrin)
What is thrombosis?
- A clotted mass of blood that is both within the unruptured cardiovascular system (not a bruise, haematoma, ecchymosis or petechia) and during life (not a post-mortem clot, not in a lab)
- It is considered abnormal
What is a thrombus made up of?
A thrombus is made of clotted blood and contains platelets, fibrin and red & white cells. It forms in flowing blood and will often have red and white laters containing red cells and platelets + fibrin.
- Lines of Zahn
What is the difference between an arterial thrombus and a venous thrombus?
- Arterial thrombi contain a higher proportion of platelets and fibrin:
- white thrombus
- associated with endothelial dysfunction/damage
- aspirin is more useful in preventing arterial thrombosis
- Venous thrombi contain a higher proportion of blood cells and fibrin
- red thrombus- associated with blood stasis and hypercoagulability
- warfarin more useful for preventing venous thrombosis
What can cause a thrombus?
Thrombosis occurs due to an imbalance between factors that promote thrombogenesis and those that promote thrombolysis.
It may be due to underlying abnormalities:
- abnormal endothelium
- abnormal blood flow
- abnormal blood contents
Explain the elements of Virchow’s Triad.
Virchow 1: Abnormal Epithelium
- Loss of endothelium exposes collagen, vWF
- Endothelial activation or dysfunction:
- may be caused by inflammatory cytokines, toxins, hypertension, cholesterol, smoking etc.
- reduces anti-coagulant activity
- increases pro-coagulant activity
- Induces thrombosis in the absence of injury
Virchow 2: Abnormal Blood Flow
- turbulence
- stasis
- loss of laminar flow
- activates endothelium
- brings platelets into contact with vessel wall
- allows any activated clotting factors to accumulate (and continue their cascade)
Virchow 3: Abnormal Blood Coagulability
- Genetic (primary): Factor V Leiden, others
- Not Genetic (secondary): Oestrogen (contraceptive pill, pregnancy); Cancer; Smoking, obesity, age etc.
What can happen to a thrombus?
- Dissolution
- Fibrinolysis: tPA, Protein C & S etc.
- less likely the older the thrombus gets
- Organisation and Recanalisation
- organisation = granulation tissue = capillaries
- Propagation
- can grow longer (and crumblier)
- Embolism
- not good
What is an embolism?
An embolus is an intravascular mass that is carried n the blood stream. It can be solid, liquid or gaseous; it is carried to some site remote from its origin or point of entrance into the blood stream.
It often blocks the vessel it lodges in.
What are some examples of embolisms?
- Pulmonary Embolus: usually from DVT; can be asymptomatic cause transient hypoxia or sudden death
- Arterial Thromboembolism: usually from atheroma or heart (atria, valves, ventricles); it will block an artery downstream and cause ischaemia and infarction
- Others: amniotic fluid embolism, septic embolism, atheroembolism, fat embolism, gas embolism
Explain the relationship between venous thrombosis and embolism?
- significant thromboemboli usually arise in the deep veins of the legs/pelvis
- usually travels through the R. side of the heart and lodges in the pulmonary arteries
- other venous emboli (ie. air emboli or embolism from IV drug use) will follow the same path.
Explain the relationship between arterial thrombosis and embolism?
- usually involved turbulence and/or platelets adhering to a dysfunctional blood vessel surface (atheroschlerosis, myocardial infarction, atrial fibrillation)
- arterial thrombosis may cause occlusion in situ
- arterial emboli will get stuck further down the artery and cause ischaemia in the organ (MI, stroke)
- emboli from the heart (or aorta) can affect any downstream organ (brain, intestine, kidneys, legs)
What is the difference between ischaemia and infarction?
Ischaemia means not enough blood supply; whereas infarction is tissue death due to inadequate blood supply.
What is the difference between hypoxia and hypoxaemia?
Hypoxia means “not enough oxygen”, and hypoxaemia means “not enough oxygen in the blood”
What are some features of iscaemia?
Ischaemia is a deficiency, real or relative, of oxygenated blood in a tissue causeing a shortage of oxygen and impaired aerobic respiration. Due to:
- local vascular narrowing or occlusion
- increased demand for ox that is not met
- systemic reduction is tissue perfusion
It may be acute or chronic ischaemia.
