Haemostasis and anticoagulants Flashcards
Define haemostasis
Haemostasis: functions to limit blood loss following vascular damage yet without compromising fluidity of blood
Define thrombosis
Thrombosis: Occlusion of a blood vessel due to intravascular blood clot or platelet clump
What mechanisms normally suppress blood coagulation and platelet activation
Non-thrombogenic surface of the endothelium
Production of Nitric Oxide and Prostacyclin by the endothelium - this inhibits platelet aggregation
Presence of natural anti-coagulants in the blood e.g. antithrombin III
What can deficiency of a clotting factor lead to?
Uncontrollable bleeding
Briefly explain the process of Haemostasis and platelet plug formation
Wound occurs:
smooth muscle vasospasm to constrict blood flow to the area.
Sub endothelial collagen is exposed to blood. Platelets adhere to the collagen and aggregate. They change shape and pseudopodia (finger-like extensions) allows them to stick to one another.
They also release chemicals from their granules. These include:
Serotonin (vasoconstriction)
Thromboxane A2 (Vasoconstriction and platted aggregation)
ADP (Platelet aggregation)
Platelets clump together to seal the area forms a platelet plug
what are coagulation factors?
Plasma proteins made by the liver that circulate in their inactive form and are activated by proteolytic cleavage to become active proteases and initiate the next step in the cascade.
What initiates the intrinsic pathway and Briefly mention the clotting factors involve in the intrinsic pathway?
Contact of blood with Exposed sub endothelial collagen fibres.
Factor 12, 11, 9, (8 assists activation of) 10.
What initiates the extrinsic pathway and Briefly mention the clotting factors involve in the extrinsic pathway?
Tissue damage Tissue factor (F3), 7, 10
Describe the common coagulation pathway
Factor 10 (prothrombinase) converts prothrombin into thrombin. THROMBIN converts fibrinogen intro fibrin which stabilises the clot and strengthens it.
what does the fibrinolytic system do?
it is a physiological repair system which dissolves blood clots.
What enzyme is involved in dissolving blood clots, what does it do and how is it made?
Plasmin. It breaks down fibrin in the clot to soluble degradation products.
Tissue Plasminogen factor converts plasminogen to plasmin
What are two types of inappropriate activation of the coagulation cascade?
Venous thrombosis
Arterial thrombosis
Describe the mechanism of venous thrombosis and how can this be dangerous
Intravascular blood clots which form in deep veins, particularly in the legs where blood flow is slow.
This can be dangerous if the clot breaks off and and circulates as it can block finer blood vessels e.g. usually pulmonary arteries.
Describe the mechanism of arterial thrombosis
Platelets aggregate (white), usually due to rupture of atherosclerotic plaque and then encapsulated by clot (red)
What are the common sites of arterial thrombosis and what do they lead to?
Cerebral artery: thrombotic stroke
Coronary artery: myocardial infarction
what is the treatment of venous thrombosis?
anticoagulant drugs
What is the treatment of arterial thrombosis?
Short term: dissolve existing clots with fibrinolytics (TPA)
Long term: Anti-platelet drugs
What is anti-thrombin III (3)?
An natural, endogenous anticoagulant which floats around in the blood stream
Give examples of anticoagulants used in the storage of blood (in vitro)
Heparin
Calcium chelators e.g. Citrate and EDTA
Give examples of anticoagulants used in the treatment of vein thrombosis
Heparin
Oral anticoagulants:
Vitamin K antagonists e.g. warfarin
Newer agents e.g. thrombin inhibitors and factor 10a inhibitors
Give the use and mechanism of action of Heparin
Heparin binds to enhances the action of anti-thrombin III. The heparin-anti thrombin 3 complex binds to and inhibits action of clotting factors 2, 9, 10, 11, 12 and immediately inhibits clotting.
Whats the difference between Low molecular weight heparin and Unfractionated Heparin ?
LMW Heparin: inhibits 10a predominantly
UH: inhibits thrombin and 10a as it is longer
How is heparin given and why?
Intravenously or subcutaneously. It is not orally active due to its negative charge so the gut cannot absorb it.
what are the uses of Heparin?
Pre eclampsia (hypertension) in pregnancy as heparin does not cross the placenta.
Deep Vein thrombosis
in vitro anticoagulant for storage of blood
Side effects of heparin?
Haemorrhage
Allergic reactions
Heparin induced thrombocytopenia
what is the role of reduced vitamin K?
reduced vitamin K is used as a cofactor for the synthesis of clotting factors (2, 7, 9 and 10)
What is needed for the reduction of vitamin K?
Vitamin K oxidoreductase
Which anticoagulant is a vitamin K antagonist?
warfarin
What is the mechanism of warfarin and administration?
It is orally active.
Warfarin block vitamin K oxidoreductase so there is no reduced Vitamin K and no clotting factors.
What drugs don’t work well with warfarin?
NSAIDs
Side effects of warfarin?
haemorrhage
Crosses blood brain barrier and placenta (not safe for pregnancy)
What is one advantage and one disadvantage of newly introduced oral anticoagulants
No need to monitor patients on them
they are expensive
List three drugs used as anti-platelet drugs
Aspirin
Clopidogrel
Abciximab
How does aspirin work?
irreversibly inhibits COX
Inhibits endothelial production of prostacyclin
how does clopidogrel work?
Blocks platelet ADP receptors so prevents platelet aggregation
Is abciximab a prescription drug?
No, it is only used once as it is antigenic e.g. used during operation
Give examples of two fibrinolytic agents?
Streptokinase
Tissue Plasminogen Activator
How does Streptokinase work?
It binds to plasminogen and activates it by inducing a conformational change.
Why is there an increased risk of haemorrhage with streptokinase?
activates plasminogen systemically so there is increased risk of haemorrhage
How does Tissue Plasminogen activator work?
only activates plasminogen bound to fibrin
what are fibronolytics used for?
dissolving blood clots following myocardial infarction or thrombotic stroke
Venous thrombosis
What are side effects of fibrinolytic agents?
haemorrhage
allergy
