Blood Coagulation Flashcards
What are the main constituents of coagulation?
- Vessel wall lined by endothelium.
- Platelets - derived from megakaryocytes in marrow.
- Coagulation factors in un-activated state.
- Inhibitors of coagulation.
- Fibrinolytic system and inhibitors.
What are coagulation factors?
- Coagulation factors = proteins which circulate in an inactive state and become activated in a cascade reaction and cause clotting.
Describe the role of endothelial cells.
- Line blood vessels and form a barrier.
- Produce thrombomodulin and heparin sulphate to inhibit thrombin production.
- Enzymes to degrade platelet granule-derived molecules.
- Prostacyclin and nitric oxide (NO) to reduce platelet adhesion.
Describe platelets.
- Fragments of megakaryocyte cytoplasm.
- Budded off into lumen of marrow sinusoids.
- Production stimulated by thrombopoietin (TPO) - liver derived.
- Cicrulate for 5-10 days with ~30% ‘stored’ in spleen.
- Form a plug when attracted by lowered prostacyclin and by collagen exposure.
- Thromboxane A2 and serotonin from platelets cause vasoconstriction.
How do platelets adhere to the vessel wall?
Platelets adhere to the vessel wall via Von Willibrand’s factor and Glycoprotein Ib.
How do platelets adhere to each other?
Platelets adhere to each other via glycoprotein IIb-IIIa and fibrinogen.
What are the functions of platelets?
- Form a plug when attracted by lowered prostacyclin and by collagen exposure.
- Granule release.
- Fibrin formation.
Describe what happens in the coagulation cascade.
- Factors present in inactive state - activated by ‘intrinsic or extrinsic’ pathway.
- Fibrin is needed to form a clot.
- Diagram:
- Black = accelerator
- Red = brakes (these try to prevent the coagulation cascade)
List the factors which inhibit coagulation.
- Protein C activated by thrombomodulin-thrombin complex.
- With co-factor - factor S - Va and VIIIa are degraded.
- Antithrombin (previously antithrombin III) inhibit Xa and IIa.
- Heparin cofactor II inhibits IIa.
- Heparin stimulated antithrombin and heparin cofactor II.
- Only a very small amount of coagulation factor is needed; its effects build faster and faster. Results in coagulation happening faster than it can be inhibited.
Describe the fibrinolytic system.
- Plasminogen activated to plasmin by tissue plasminogen activator (tPA) - from endothelial cells.
- Fibrin broken down into ‘fibrin degradation products’ including D dimers - a measurement of fibrinolysis (a measure of how well a clot has broken down).
- Inhibitors of fibrinolytic system.
- Theraputic use with eg. streptokinase to tPA for ‘clot busting’ eg acute myocardial infarction or thrombotic stroke.
What is fibrin?
Fibrin = meshwork of protein that can be brokwn down into its constituent parts.
What is the ‘gold-standard’ time frame for thrombolysis in stroke treatment?
Gold standard for stroke treatment - ideally in under 3 hours.
What is clot retrieval?
- Clot retrieval - putting a cathater in to pull the clot out.
- Arguably more effective than dissolving the clot.
How do you measure coagulation?
- Full blood count - includes platelet count / size / granules, but is a poor assessment of platelet function - specialised tests of aggregation can be done.
- Ref range 150-400 x109 /L
What is caused by an FBC <30-50 x109/L?
And <10 x109/L?
- Easy bruising and purpura when FBC <30-50 x109 /L (thrombocytopaenia).
- Risk of major bleeding if <10 x109/L.
Describe a bleeding time test.
- In vivo test of overall clotting - mainly platelet function.
- Lots of poorly controlled variables, so not often done.
