Blood coagulation Flashcards

1
Q

What is disseminated intravascular coagulation (DIC)?

A
  • 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
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2
Q

What is haemostasis?

A
  • 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
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3
Q

What are the 3 key components of haemostasis?

A
  • Endothelium
  • Platelets
  • Coagulation
  • Fibrinolysis
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4
Q

What makes a blood clot?

A
  • Fibrin mesh - comes out of solution to form and strengthen the clot
  • Platelets
  • RBCs - change shape
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5
Q

What are 3 stages of haemostasis?

A
  • 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)
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6
Q

What happens during primary haemostasis?

A
  • 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
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7
Q

What happens in secondary haemostasis?

A
  • 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
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8
Q

What are the two main initiators of clotting?

A
  • Tissue damage

- Foreign surface contact

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9
Q

Where are most of the factors produced?

A

Liver

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

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10
Q

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

A

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

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11
Q

How do we amplify the thrombin formation?

A
  • 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
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12
Q

What is the main function of fibrinolysis?

A
  • Clot limiting mechanism

- Repair and healing mechanism

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13
Q

What are the main players in fibrinolysis?

A
  • Plasminogen
  • tPA and urokinas (uPA) - clot busters
  • Plasminogen activator inhibitor 1/2
  • a2-plasmin inhibitor
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14
Q

What is the process of fibrinolysis?

A
  • 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
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15
Q

Why do we do D-dimer tests?

A

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

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16
Q

What can we use for therapeutic thrombolysis?

A
  • tPA and a bacterial activator streptokinase are used for MI (clot busters)
17
Q

What keeps haemostasis in equilibrium?

A

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

  • more anticoagulation -> bleeding
  • More coagulation -> bleeding
18
Q

What is ecchymosis?

A
  • Easy bruising

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

19
Q

What is the main principles of clotting tests?

A
  • 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
20
Q

What does prothrombin time (PT) measure?

A
  • 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
21
Q

What does Activated partial thromboplastin time (APTT) measure?

A
  • Sensitive to the intrinsic pathway

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

22
Q

What does thrombin time measure (TT)?

A
  • 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
23
Q

What problems may you have with the phlebotomy?

A
  • 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
24
Q

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

A
  • 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)