Blood coagulation Flashcards
What is disseminated intravascular coagulation (DIC)?
- if you have an infection, you can cut off all of the blood so that it doesnt spread, giving an infarcted area
- Eg gangrene in the fingers
What is haemostasis?
- Life preserving process designed to maintain blood flow
- Responds to tissue injury
- Curtail blood loss
- Restore vascular integrity and promote healing (WBCs come in and sort it out)
- Limit infection
What are the 3 key components of haemostasis?
- Endothelium
- Platelets
- Coagulation
- Fibrinolysis
What makes a blood clot?
- Fibrin mesh - comes out of solution to form and strengthen the clot
- Platelets
- RBCs - change shape
What are 3 stages of haemostasis?
- Primary - vasoconstriction (immediate), platelet adhesion (within secs), platelet aggregation and contraction (within mins)
- Secondary - activation of coagulation factors (within secs), formation of fibrin (within mins)
- Fibrinolysis - shapes the clot, gets it to stick where it should be (within mins), lysis of the plug (within hours)
What happens during primary haemostasis?
- Usually collagen and tissue factor are hidden by the endothelium
- When endothelium is damaged, TF produces a small amount of thrombin and the sticky collagen is exposed
- vWF unravels and sticks platelets together and to the collagen, acting as an anchor to the damaged endothelium (adhesion)
- Platelets change shape, producing pseudopodia and increasing the SA. Also release attractant chemicals (secretion)
- There is then more vWF and more recruitment of platelets, which all aggregate. Then contracts to form a dense adherent plug -> clot
What happens in secondary haemostasis?
- TF binds to fVIIa - complex has the power to activate another factor (fXa), which can activate thrombin
- Thrombin causes fibrinogen to be cleaved to fibrin
- fibrin mesh binds and stabilises platelet plug and other cells
What are the two main initiators of clotting?
- Tissue damage
- Foreign surface contact
Where are most of the factors produced?
Liver
- liver disease can cause reduction in clotting factors and so lots of bleeding
Why does the amount of thrombin produced have to be amplified?
The amount produced by TF-FVIIa isnt enough to turn everything on
How do we amplify the thrombin formation?
- Thrombin works with VIIIa and IXa on a platelet surface
- These all work together with the activated platelet to cause the thrombin burst
- Can then change fibrinogen to fibrin, to form the mesh
What is the main function of fibrinolysis?
- Clot limiting mechanism
- Repair and healing mechanism
What are the main players in fibrinolysis?
- Plasminogen
- tPA and urokinas (uPA) - clot busters
- Plasminogen activator inhibitor 1/2
- a2-plasmin inhibitor
What is the process of fibrinolysis?
- tPA converts plasminogen to plasmin
- Plasmin can break down the fibrin clot
- D-dimers are generated when cross-linked fibrin is degraded
- Fibrin degradation products (FDPs) are produced if non-crosslinked fibrin or fibrinogen is broken down
Why do we do D-dimer tests?
To see if someone has had a clot that has been broken down
What can we use for therapeutic thrombolysis?
- tPA and a bacterial activator streptokinase are used for MI (clot busters)
What keeps haemostasis in equilibrium?
Levels of fibrinolytic factors and anticoagulant proteins vs coagulation factors and platelets
- more anticoagulation -> bleeding
- More coagulation -> bleeding
What is ecchymosis?
- Easy bruising
- Get it in virtually all bleeding disorders, and often in normals
What is the main principles of clotting tests?
- Incubate plasma with reagents necessary for coagulation - mimic forming a clot
- Phospholipid, co-factors
- Trigger/ activator
- Calcium
- Then measure time take to form the fibrin clot
What does prothrombin time (PT) measure?
- Measures the extrinsic pathway (TF is extrinsic to the blood as hidden by endothelium)
- To mimic this you add TF, which binds to FVIIa, which will start the process
- Should take 11-13 secs
What does Activated partial thromboplastin time (APTT) measure?
- Sensitive to the intrinsic pathway
- If you add a foreign substance, you can test the APTT
What does thrombin time measure (TT)?
- Add some thrombin
- Should be able to convert any fibrinogen in the tube into fibrin
- Shows that the end part of the process is working
What problems may you have with the phlebotomy?
- Blue tube is has to be completely filled due to the sodium citrate added
- Need to have it to chelate the calcium, stopping it from clotting
- There is a specific amount to fill the whole tube to keep the same ratio
- Under filling gives grossly inaccurate results
- Heparin contamination
- Wrong label
- Slow fill
- Vigorous shaking
- Difficult venepuncture
How do we know if the increased APPT or PT is due to deficiency or inhibitor?
- Mix patient and normal plasma in equal volumes (50:50 mix)
- repeat abnormal coagulation test
- If the test normalises, then it was because there were factor deficiencies that have been rectified by normal plasma
- Test remains abnormal - means that there is an inhibitor (usually Ab)
