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Week 3 - haematology > Basic blood coagulation > Flashcards

Basic blood coagulation Flashcards

1
Q

What is required for the process of coagulation

A
  • Functioning platelets
  • Functioning endothelium
  • Coagulation factors
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2
Q

What happens when you cut yourself?

A
  • Blood vessel damage
  • This disrupts the endothelium
  • Leading to the exposure of tissue factor and collagen
  • This triggers primary haemostatsis, platelets are recruited
  • Secondary haemostasis means the coagulation factors are activated
  • primary and secondary haemostasiss occurs at the same time
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3
Q

Explain primary haemostasis

A
  • Hole - present von willebrand factor
  • Platelets get attracted through glycoprotein receptors IB59, allowing platelets to adhere to von willebrand factor
  • The platelets then get activated and release their granular content
  • This causes more platelets to be attracted -> platelet aggregation
  • They also expose phospholipids
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4
Q

Explain secondary haemostasis

A 
•Activation of the coagulation factors 
•cascade of events occurs: 
 - initiation via the extrinsic pathway 
 - propagation via the intrinsic pathway 
 - thrombin generation 
 - fibrin production - the 'clot'
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5
Q

What does every step of the initiation of the coagulation cascade require?

A
  • Phospholipid (from the platelet surface)

* Calcium (found in the blood)

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6
Q

Fully explain the initiation of the coagulation cascade

A
  • Tissue factor activated Factor VII
  • Activated VII (VIIa) activates Factor X
  • Xa + II (prothrombin) and Va = prothrombinase complex which allows the activation of prothrombin to thrombin
  • IIa (thrombin) activates XIII to XIIIa and turns fibrinogen into fibrin
  • Fibrin is activated by XIIIa to cross linked fibrin
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7
Q

Fully explain the propagation of the coagulation cascade

A
  • Thrombin (IIa) activates VIII and XI
  • XIa activates IX
  • IXa and VIIIa activate factor X
  • Xa+Va activates II (prothrombin) to thrombin
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8
Q

Explain the regulation of the coagulation cascade

A
  • Factor Xa stimulates Tissue Factor Pathway Inhibitor (TFPI) inhibiting the activation of Factor VII
  • Thrombin binds to the receptor thrombomodulin in the endothelium leading to the activation of protein C to APC (activated Protein C)
  • APC and Protein S down regulates Va and VIII
  • Antithrombin down regulates VIIa, IIa, XIa, IXa, Xa
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9
Q

Explain fibrinolysis

A
  • Fibrin is converted to cross linked fibrin by XIIIa
  • Plasmin stimulates tPA and uPA
  • plasminogen is converted to plasmin by tPA and uPA
  • Cross linked fibrin + plasmin -> Fibrin degrading products (FDPs) including D dimers
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10
Q

What are the assessments of primary haemostasis?

A
  • In vivo: bleeding time (puncture the skin and time how long until stops
  • Ex vivo: FBC (platelet count), platelet function (light transmission aggregometry)
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11
Q

Explain light transmission aggregometry

A
  • Take platelet rich plasma and add chemical agonists to make platelets aggregate
  • Pass light through the sample
  • As they clump, less light passes through the sample to the detector
  • Graph produced: normal = dips slightly then steep increase that levels off
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12
Q

What are the assessments of secondary haemostasis?

A
  • Prothrombin time
  • Activated partial thromboplastin time (APTT)
  • Thrombin clotting time (TCT)
  • Individual coagulation factor assays
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13
Q

What are the pre-analytical sample requirements for the coagulation tests?

A
  • Citrate sample to chelate all calcium
  • Centrifuge to separate the cellular components and to make platelet poor plasma to take out the effect the platelets have on the clotting cascade
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14
Q

What are the principles of the coagulation tests?

A
  • Add reagents to Platelet Poor Plasma (PPP)
  • Perform assay at body temperature (37 degrees)
  • Measure time for clot to form from the addition of the reagents
  • All results are expressed in seconds/ ratio to normal plasma (normal result 1.0)
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15
Q

What is prothrombin time a measure of?

A

It simulated activation via the extrinsic pathway

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16
Q

What do you add to measure prothrombin time?

A
  • Patient plasma and thromboplastin (tissue factor and phospholipids)
  • Add calcium
17
Q

Explain results of prothrombin time

A

•Measure time taken for a clot to form, normal is 10-13 seconds
•Expressed as a ratio: patient’s PT/average of 20 normal PTs
- normal ratio is 1.0-1.2

18
Q

What does Prothrombin time depend on?

A
  • Factors in the extrinsic and common pathways
  • factors VII
  • And factors X, V, II and fibrinogen
19
Q

What is international normalised ratio?

A

The standardised form of prothrombin time

20
Q

What is INR used for?

A

The monitoring of oral coumarins e.g. warfarin (Vitamin K dependent coagulation factors: II, VII, IX and X)

21
Q

How do you calculate a patients INR?

A
  • Patients TP/average of 20 normal PTs
  • Result is factored by international sensitivity index ISI
  • Every thromboplastin has its own ISI
22
Q

What is activated partial thromboplastin time a measure of?

A

Stimulates activation via the intrinsic pathway

23
Q

Describe how to measure APTT

A
  • Add plasma, contact factor (kaolin or silica) and phospholipid
  • Warm to 37 degrees
  • Add calcium
  • Time taken to clot
24
Q

What is the normal APTT range?

A

26-38 seconds

25
Q

What does APTT depend on?

A
  • Factors in the intrinsic and common pathways

* VIII, IX, XI and XII and X, V, II and fibrinogen

26
Q

What is thrombin clotting time a measure of?

A

Measure of conversion of fibrinogen to fibrin clot

27
Q

Describe how to measure TCT

A 
•At 37 degrees add: 
 - patient plasma 
 - bovine thrombin 
 - less calcium or phospholipid dependent 
•Measure time to clot 
•Ratio
28
Q

What is the normal TCT?

A

10-16 seconds

29
Q

What does thrombin clotting time depend on?

A
  • How much fibrinogen is present in the plasma

* How well that fibrinogen functions

30
Q

What will TCT be prolonged by other than how much fibrinogen/how well fibrinogen functions?

A
  • Inhibitors of thrombin (e.g. heparin, dabigatran)
  • FDPs (fibrin degradation product)
  • Inhibitors of fibrin polymerisation (paraproteins)
31
Q

Which factors are only involved in the intrinsic pathway?

A
  • VIII
  • IX
  • XI
  • XII
32
Q

Which of the clotting factors are involved in the common pathway?

33
Q

Which of the clotting factors are involved only in the extrinsic pathway?

34
Q

Only abnormal Prothrombin time

A

•Low factor VII

35
Q

Only an abnormal APTT

A
  • Low FVIII, IX, XI or XII
  • Lupus anti-coagulant
  • Intrinsic pathway, have an increased thrombosis risk
36
Q

Abnormal APTT and PT

A
  • Common pathway factor low
  • Multiple factors low
  • May be DIC or Liver disease
37
Q

What factors are vitamin K dependent?

A

II, VII, IX and X

38
Q

Explain the regulation of fibrinolysis

A
  • alpha 2 antiplasmin down regulates plasmin
  • Plasminogen activator inhibitors down regulate tPA and uPA
  • TAFI down regulates uPA

Week 3 - haematology (17 decks)

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