Flashcards in MoD 5 Deck (55):
What four things does successful haemostasis depend upon?
1. Vessel walls
3. Coagulatory system
4. Fibrinolytic system
Which systems oppose each other to regulate haemostasis?
The coagulatory and fibrinolytic systems
How do blood vessels contribute to haemostasis?
Arteries, veins and capillaires constrict to reduce blood flow (and therefore blood loss) in a mechanism that is not fully understood.
How do platelets contribute to haemostasis?
1. Adhere to the vessel walls
2. Adhere to each other
3. Form a platelet plug
4. Platelet release reaction
What are platelets derived from?
What is the platelet release reaction?
Once platelets adhere they release certain molecules which help stimulate platelet plug formation and the coagulatory system.
Which molecules released in the platelet release reaction help stimulate platelet plug formation?
ADP, thromboxane A2
Name a molecule released in the platelet release reaction that helps stimulate coagulation?
Platelet factor 3
What is coagulation?
A cascade in which a series of inactive components are converted to active components. This results in fibrinogen being converted to fibrin which polymersises and along with platelets forms the haemostatic plug.
What is prothrombin time a useful measure of?
How effective the clotting cascade is in an individual.
Why is coagulation tightly regulated?
1ml of blood contains enough thrombin to convert all the fibrinogen in the body to fibrin. Therefore a balance or proagulant and anti-coagulant forces is required to prevent inappropriate coagulation.
What is thrombophilia?
Thrombophilia is an abnormality of blood coagulation that increases the risk of thrombosis.
List some thrombin inhibitors:
Alpha 1 anti-trypsin
Alpha 2 macroglobulin
What can be the consequences of inherited deficiencies in protein C and protein S?
Increased risk of thrombosis.
What is fibrinolysis?
The breakdown of fibrin.
How does fibrinolysis occur?
Plasminogen activators convert plasminogen to plasmin. Plasmin break downs fibrin.
What is the role of protein C in the fibrinolytic system?
Activated by thrombin binding to the endothelial receptor, thrombomodulin, it degrades blood clotting factors (Va and VIIIa).
What is the role of anti-thrombin III (AT3) in the fibrinolytic system?
It binds very tightly to thrombin and Factor X. This is enhanced by heparin binding (though heparin-bound AT3 cannot bind to thrombin attached to thrombomodulin receptors).
Name two plasminogen activators:
Streptokinase and t-PA.
Fibrinolytic therapy is widely used e.g. to to break down fibrin polymers in thrombi blocking the coronary arteries. What molecules do they inject in this therapy?
Streptokinase and t-PA.
What gives the endothelium some anti-thrombin properties?
1. Plasminogen activators
2. Prostacyclin (inhibits platelet activation)
3. Nitric oxide (vasodilator?)
4. Thrombomodulin (cofactor of thrombin-induced activation of protein C)
What is thrombosis?
The formation of a solid mass of blood WITHIN the circulatory system (during life).
What are the three main categories of causes of thrombosis?
1. Abnormalities of the vessel wall
2. Abnormalities of blood flow
3. Abnormalities of blood components
What types of abnormalities to vessel walls can cause thrombosis?
2. Direct injury
What types of abnormalities to blood flow can cause thrombosis?
What types of abnormalities to blood components can cause thrombosis?
1. Smoking -> inherently more coagulable blood
2. Post-partum hypercoaguability
What do arterial thrombi look like?
1. Pale (lower RBC content than venous thrombi)
3. Lines of Zahn (laminations -> indicate high blood flow when occurred)
4. Lower cell content
What do venous thrombi look like?
3. Deep red
4. Higher cell content
What are the 5 main outcomes of thrombosis?
What does the outcome 'lysis of thrombosis' involve?
Fibrinolytic system activates and completes dissolves the thrombus restoring blood flow to exactly as it was before.
When is lysis of a thrombosis likely to occur?
Most likely when the thrombus is small.
What does the outcome 'propagation of thrombosis' involve?
This occurs when the stagnant blood distal to the thrombus causes turbulence when new vessels join downstream. This turbulence creates a new thrombus, which causes stagnation downstream and the cycle continues resulting in a progressive spread of thrombus (which get progressively bigger as the veins/arteries get larger) - distally in arteries and proximally in veins.
What does the outcome 'organisation of thrombosis' involve?
This is when there is nor restoration of blood flow to a vessel after it has been blocked by a thrombus. Instead a repair process occurs which involves the ingrowth of fibroblasts and capillaries (similar to granulation tissue), however the lumen remains blocked.
What does the outcome 'recanalisation of thrombosis' involve?
This is when one or more channels are formed by recanalisation through an organising thrombus. This re-establishes blood flow but usually incompletely.
What does the outcome of a thrombosis, 'embolism', involve?
This is when part of a thrombus breaks off and travels through the bloodstream, lodging at a distal site.
How does a pulmonary embolism occur?
A thrombus forms in the deep veins of the legs, propagates and then embolises to the right side of the heart and into the pulmonary arteries becoming lodged when they narrow.
What are the effects of arterial thrombosis?
3. Depends on site and collateral circulation
How are the effects of an arterial thrombosis different on an individual which chronic arterial disease compared to a individual with no previous history of arterial disease?
Collateral circulation is more likely to occur where there has been chronic arterial disease and therefore has had time to build-up.
What are the effects of venous thrombosis?
1. Congestion - overfilling and distension of the veins with blood
What is an embolism?
The blockage of a blood vessel by solid, liquid or gas at a site distant from its origin.
What are type are over 90% of emboli?
List some types of emboli other than thrombo-emboli?
2. Amniotic fluid
4. Medical equipment
5. Tumour cells
6. Cholesterol - e.g. from athersclerotic plaque
What is a dangerous cause of air emboli?
Slit throat -> air into external jugular.
Where do thrombo-emboli from the heart travel?
Via the aorta to the renal, mesenteric and other arteries.
Where do thombo-emboli from the atheromatous carotid arteries travel?
Up to the brain
Where do thombo-emboli from the atheromatous abdominal aorta travel?
To the arteries of the legs
What are predisposing factors of DVT?
1. Immobility/ bed rest
3. Pregnancy and post-partum
4. Oral contraceptives (especially oestrogen)
5. Severe burns
6. Cardiac failure
7. Disseminated cancer
What prophylactic measures can be taken for DVT?
1. High risk patients identified and offered prophylaxis:
(i) Heparin sub-cutaneously
(ii) Leg compression during surgery
How does heparin reduce the risk of DVT?
Heparin binds to and activates anti-thrombin III which binds to thrombin and other factors involved in blood clotting deactivating them.
How can DVT be treated?
1. Intravenous heparin
2. Oral warfarin
But these don't dissolve the thrombus
How does warfarin reduce the risk of thrombosis?
Warfarin acts by inhibiting the synthesis of vitamin K-dependent clotting factors and therefore acts as an anti-coagulant.
What are the effects of a pulmonary embolism?
1. Massive PE -> >60% reduction in blood flow = rapidly fatal
2. Major PE -> medium-sized vessels blocked -> SOB +/- cough and blood stained sputum
3. Minor PE -> small peripheral pulmonary arteries blocked. Asymptomatic or SOB.
What are the effects of recurrent minor PE?
Leads to pulmonary hypertension and therefore major long-term effects.
What is a transient ischaemic attack? What are the consequences of one?
It is a minor stroke. It is a sign of high-risk of having a stroke.