Blood coagulation

Question 1

What is disseminated intravascular coagulation (DIC)?

Answer 1

• 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

Question 2

What is haemostasis?

Answer 2

• 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

Question 3

What are the 3 key components of haemostasis?

Answer 3

• Endothelium
• Platelets
• Coagulation
• Fibrinolysis

Question 4

What makes a blood clot?

Answer 4

• Fibrin mesh - comes out of solution to form and strengthen the clot
• Platelets
• RBCs - change shape

Question 5

What are 3 stages of haemostasis?

Answer 5

• 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)

Question 6

What happens during primary haemostasis?

Answer 6

• 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

Question 7

What happens in secondary haemostasis?

Answer 7

• 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

Question 8

What are the two main initiators of clotting?

Answer 8

• Tissue damage

- Foreign surface contact

Question 9

Where are most of the factors produced?

Answer 9

Liver

- liver disease can cause reduction in clotting factors and so lots of bleeding

Question 10

Why does the amount of thrombin produced have to be amplified?

Answer 10

The amount produced by TF-FVIIa isnt enough to turn everything on

Question 11

How do we amplify the thrombin formation?

Answer 11

• 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

Question 12

What is the main function of fibrinolysis?

Answer 12

• Clot limiting mechanism

- Repair and healing mechanism

Question 13

What are the main players in fibrinolysis?

Answer 13

• Plasminogen
• tPA and urokinas (uPA) - clot busters
• Plasminogen activator inhibitor 1/2
• a2-plasmin inhibitor

Question 14

What is the process of fibrinolysis?

Answer 14

• 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

Question 15

Why do we do D-dimer tests?

Answer 15

To see if someone has had a clot that has been broken down

Question 16

What can we use for therapeutic thrombolysis?

Answer 16

• tPA and a bacterial activator streptokinase are used for MI (clot busters)

Question 17

What keeps haemostasis in equilibrium?

Answer 17

Levels of fibrinolytic factors and anticoagulant proteins vs coagulation factors and platelets

• more anticoagulation -> bleeding
• More coagulation -> bleeding

Question 18

What is ecchymosis?

Answer 18

• Easy bruising

- Get it in virtually all bleeding disorders, and often in normals

Question 19

What is the main principles of clotting tests?

Answer 19

• 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

Question 20

What does prothrombin time (PT) measure?

Answer 20

• 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

Question 21

What does Activated partial thromboplastin time (APTT) measure?

Answer 21

• Sensitive to the intrinsic pathway

- If you add a foreign substance, you can test the APTT

Question 22

What does thrombin time measure (TT)?

Answer 22

• 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

Question 23

What problems may you have with the phlebotomy?

Answer 23

• 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

Question 24

How do we know if the increased APPT or PT is due to deficiency or inhibitor?

Answer 24

• 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)