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Haematology > Blood Coagulation,Haemostasis and its investigation > Flashcards

Blood Coagulation,Haemostasis and its investigation Flashcards

1
Q
  1. What is haemostasis?
A

o Protective process evolved in order to maintain a stable physiology.
o “An explosive reaction designed to curtail blood loss, restore vascular integrity and ultimately preserve life”.

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2
Q
  1. What is an initiator of haemostasis
A

Infection

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3
Q
  1. What is an endotoxin and what can it initiate?
A

Endotoxins are basically pyrogens found in gram- bacteria cell walls
They can initiate a primitive coagulation pathway

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4
Q
  1. What is the haemolymph?
A

Its basically the fluid equivalent of blood in most inverter-brae animals eg horseshoe crab
Contains proteins of the coagulation system as well as proteins/peptides of the immune system

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5
Q
  1. The haemolymph contains amebocytes- what do they do?
A

Amebocytes are mobile cells - they allow the infection to be contained to stop access to other vital organs

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6
Q
  1. What is Disseminated intravascular coagulation (DIC)?
A

condition in which small blood clots develop throughout the bloodstream, blocking small blood vessels.

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7
Q
  1. Explain the appearance of DIC?
A

Looks like small blood spots under the skin

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8
Q
  1. What are the four key concepts in haemostasis?
A
  • Endothelium
  • Coagulation
  • Platelets
  • Fibrinolysis
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9
Q
  1. What makes a blood clot?
A

Fibrin Mesh
Platelets
RBC’s

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10
Q
  1. What is a haemostasis overview in 4 steps?
A 
-Vessel Damage and 
 Blood loss
-Vascular Spasm
-Platelet Plug Forms
-Coagulation
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11
Q
  1. We can break the haemostatic system into 3 phases:
    What does the phase “Primary Haemostasis”
    include and give a time frame for each step:
A
  • Vasoconstriction (immediate)
  • Platelet adhesion (within seconds)
  • Platelet aggregation and contraction (within minutes)
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12
Q
  1. We can break the haemostatic system down into 3 phases:

What does the phase “ Secondary Haemostasis” include and give a time frame for each step:

A

Activation of coagulation factors (within seconds)

Formation of fibrin (within minutes)

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13
Q
  1. We can break the haemostatic system down into 3 phases:

What does the phase “ Fibrinolysis” include and give a time frame for each step?

A

Activation of fibrinolysis (within minutes)

Lysis of the plug (within hours)

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14
Q
  1. What is Von Willebrand factor?
A

Multi-meric structure that becomes unravelled and active upon sheer stress. It acts as an anchor for platelets allowing their adhesion

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15
Q
  1. What activates Von Willebrand factor?
A

When tissue damage exposes the endothelium to tissue factor, it causes von Willebrand factor to become activated.

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16
Q
  1. What is the aim of a ‘platelet plug’ ?
A

Platelet Aggregation —> Platelet Plug —-> Prevents excessive blood loss at the injury site

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17
Q
  1. What activates the coagulation process?
A

vWF Activation —> Platelet Adhesion to exposed endothelium wall

Exposed TF –> Production of small amount of thrombin

-> Activates Coagulation process

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18
Q
  1. What is the role of platelets in coagulation process within primary haemostasis?
A

Activation:
- Thrombin activates platelets

Aggregation:
-Platelets release more attractant chemicals to attract more platelets

Contraction:
- Activated Platelets –> Conformational change –> Contract —> Form a dense plug–> Provides phospholipid surface for secondary haemostasis to take place

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19
Q
  1. Where is the majority of coagulation factors produced in?
A

The Liver

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20
Q
  1. What is the function of fibrinogen?
A

Forms clot (Fibrin)

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21
Q
  1. What is the function of Prothrombin(II) ?
A

In its active form (IIa) it activates I,V,VII,XIII,Protein C and Platelets

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22
Q
  1. What is the function of tissue factor?
A

Co-factor of Vlla

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23
Q
  1. What in the function of Von Willebrand factor?
A

Binds to Vlla

Mediates Platelet Adhesion

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24
Q
  1. Which deficiency causes bleeding:
    -FVII deficiency
    OR
    -FXII deficiency
A

FVII causes bleeding bro

FXII is not associated with bleeding

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25
Q
  1. What does each reaction in the waterfall cascade thing require?
A

Ca2+
Phospholipid
+ or - Specific Co-Factors

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26
Q
  1. What activates the whole cascade?
A

o Extrinsic tissue damage :
Factor 7 combines with Tissue Factor forming a complex that activates other proteins in the cascade.
• Measured with prothrombin time.

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27
Q
  1. What is the REVISED Initiation process of the cell-based model of coagulation?
A 
o	TF (outside the lumen normally) forms a TF-FVIIa complex. 
o	This then recruits FX and FV to the exposed endothelial, these form small quantities of thrombin.
o	Thrombin activates platelets and other plasma-borne factors e.g. FVIII and FIX.
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28
Q
  1. What is the amplification process of the cell-based model of coagulation?
A

These factors enable FX and FV to bind to platelet surfaces which leads to a thrombin burst.

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29
Q
  1. What is the propagation process of the cell-based model of coagulation?
A

oThrombin burst then allows for large-scale production of fibrin which is needed for a clot.

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30
Q
  1. What is the whole process of cell-based model of coagulation?
A

o TF (outside the lumen normally) forms a TF-FVIIa complex.
o This then recruits FX and FV to the exposed endothelial, these form small quantities of thrombin.
o Thrombin activates platelets and other plasma-borne factors e.g. FVIII and FIX.
o These factors enable FX and FV to bind to platelet surfaces which leads to a thrombin burst.
o Thrombin burst then allows for large-scale production of fibrin which is needed for a clot.

31
Q
  1. What is fibrinolysis?
A

o Series of tightly regulated enzymatic steps: Feedback potentiation & inhibition

32
Q
  1. What is the main function of fibrinolysis?
A

clot limiting mechanism and repair and healing mechanism.

33
Q
  1. What 5 key things do you need for fibrinolysis to take place?
A 
•	Plasminogen, 
•	Tissue plasminogen 
        activator (t-PA) & 
        urokinase (u-PA)
•	Plasminogen activator 
        inhibitor -1 and -2
•	α2-plasmin inhibitor
34
Q
  1. What is the process of fibrinolysis?
A

o Plasminogen is converted into plasmin by tissue plasminogen activator, tPA.
o Plasmin forms a cross-linked fibrin clot.
o Cross-linked fibrin clot degradation: D dimers.
o Non crosslinked fibrin/fibrinogen degradation: Fibrin Degradation Products (FDP).
o tPA and streptokinase (bacterial activator) are used in therapeutic thrombolysis for myocardial infarction (clot busters).

35
Q
  1. What does normal haemostasis have a balance between?
A

Haemostasis (Fibrinolytic Factors , anticoagulant proteins) and thrombosis (coagulation factors, platelets)

36
Q
  1. What is thrombosis?
A

Formation of blood clot- increase coagulation factors and platelets (decrease fibrinolytic factors and anticoagulant proteins)

37
Q
  1. What is chronic venous insufficiency?
A

condition that occurs when the venous wall in the leg veins are not working effectively
CVI causes blood to “pool” or collect in these veins,

38
Q
  1. What are some symptoms of Chronic Venous Insufficiency?
A

Atrophic changes (degenerative)
Hyperpigmentation
Ulceration
Infection

39
Q
  1. What happens if the normal haemostasis balance tips so that there is an increase in fibrinolytic factors and anticoagulant proteins?
A

Increased Bleeding

40
Q
  1. What is Ecchymosis?
A
  • Easy bruising from blood under the skin

- Present in virtually all bleeding disorders and often in normal

41
Q
  1. To test why a patient has excessive bleeding

May do a FBC and blood film, what does this count and what can this test for?

A

Tells us:

  • Platelet Count
  • Platelet Morphology

Tests for:
-Thrombocytopenia (platelet deficiency) eg ITP or DIC

42
Q
  1. To test why a patient has excessive bleeding we

may do coagulation tests what does this count and what can this test for?

A

Tells us:

  • Prothrombin Time (PT)
  • APTT/KCCT - activated partial thromboplastin time
  • Thrombin Time (TT)
  • Mixing studies
  • Factor Assays

Tests for:

  • Extrinsic and Intrinsic pathway
  • Common pathway
  • Fibrin Formation
43
Q
  1. to test why a patient has excessive bleeding we

may do platelet function tests what does this count and what can this test for?

A

Tells us:
Von Willebrand factor
Platelet function analyser (PFA-100)
Platelet aggregometry(how quickly platelets aggregate)

Detects:
Platelet defects
Von Willebrand disease

44
Q
  1. What are two global tests for bleeding?
A

Thromboelastography (tests coagulation efficiency).

Thrombin generation

45
Q
  1. What is the principle of clotting tests?
A

o Incubate plasma with reagents necessary for coagulation.
• Phospholipid, co-factors e.g. calcium, trigger or activator.
o Measure time taken to form fibrin clot.

46
Q
  1. What is prothrombin time? What is sensitive to?
A

PT= Time for blood to clot
Sensitive to EXTRINSIC pathway ( lesser extent to common pathway)
Tissue factor driven

47
Q
  1. What is Activated Partial Thromboplastin Time (APTT) sensitive to?
A

o Sensitive to intrinsic pathway and to a lesser extent common pathway.
o Contact activated.

48
Q
  1. What is Thrombin Time (TT) sensitive to?
A

o Sensitive to defects in conversion of fibrinogen to fibrin.

49
Q
  1. Explain a brief overview of the coagulation pathways?
A

You have the intrinsic pathway (affect APTT) and the Extrinsic pathway (affect PT), these both lead into the Common pathway (Affect Thrombin time) which results in a fibrin clot

50
Q
  1. What is one disadvantage of tests that tell us about clotting time?
A

-NO info on the amplification or lysis process

51
Q
  1. Why is it important that testing is done correctly- how do we ensure it is done correctly?
A

-> Needs to be done correctly = Reliable results

  • > Correctly labelled for identification
  • > Selected/tested in the proper order and time
52
Q
  1. The accuracy of haemostasis laboratory tests depends on quality of the specimen:
    - What % of sodium citrate is blood anti coagulated with?
    - What is the proportion of blood and anti-coagulant in the testing tube?
A

3.2% (0.109M) Sodium Citrate

Most tubes contain 0.3mL anticoagulant -for 2.7 mLs of blood

53
Q
  1. What is the consequence of under filling the tube?
A

-Grossly inaccurate Tubes

54
Q
  1. What are 4 types of pre-analytical errors:
A
  1. Problems with blue-top tube
  2. Laboratory Errors
  3. Biological Effects
  4. Problems with Phlebotomy (surgical opening on vein)
55
Q
  1. What could go wrong the blue-top tube?
A
  • Tubes are filled partially
  • Citrate Evaporates
  • Vacuum leak
56
Q
  1. What biological effects could cause pre-analytical errors?
A

Hct (RBC count) is either >55 or <15

  • Lipaemia (presence of high emulsified fat in blood)
  • hyperbilirubinaemia
  • haemolysis ( rupture of RBC)
57
Q
  1. What laboratory errors could there be?
A
  • Delay in testing = prolonged incubation at 37 degrees celsius
  • Freeze/thaw deterioration
58
Q
  1. What kind of problems could you have with phlebotomy (opening of the vein)
A
  • Heparin Contamination
  • Wrong label
  • Vigorous Shaking
  • Slow fill/ underfill
  • Difficult Venipuncture
59
Q
  1. Compare manual coagulation to automatic?
A

Manual Coagulation = Tilt 3 times every 5sec’s at 37 degrees

Automatic = Computer Used

60
Q
  1. Why would you do a mixing study?
A

When the clotting time is too long - test to see why its taking so long to clot, inhibitors or factor deficiencies

61
Q
  1. How does a mixing study work?
A

o Mix patient and normal plasma in equal volumes (50:50 mix) and repeat the abnormal coagulation test.
o If the test normalises, it shows factor deficiencies but if the test remains abnormal, it shows inhibitors such as antibodies.

62
Q
  1. What would you expect in a result where a patient with a factor deficiency did a mixing study?
A

so the test plasma would have a FVIII:C (activity of FVIII) of <1 (LOW) and an APTT of 95s (HIGH)
The control plasma would have a FVIII:C of 100 and APTT of 28s (NORMAL)

the 50:50 mix would have a FVIII: C of 50 and APTT of 32s
Its borderline normal-can confirm a factor deficiency

63
Q
  1. What would you expect in a result where a patient with inhibitors (like antibodies) does a mixing study?
A

so the test plasma WITH ANTIBODY would have a FVIII:C (activity of FVIII) of <1 (LOW) and an APTT of 95s (HIGH)
The control plasma would have a FVIII:C of 100 and APTT of 30s (NORMAL)

The mix will have a FVIII:C of 10 and APTT 75s , so still abnormal
We can confirm its an inhibitor

64
Q

64.
Patient X , has an Abnormal PT and Abnormal APTT
You repeat tests with a 50:50 mix
What should you test for if the 50:50 mix is ABNORMAL?

A

You would test for inhibitor activity eg
Specific ones like Factors V,X,II and I - which are rare
or
Non-Specific like anti-phospholipid which is more common

65
Q

65.
Patient X, has an Abnormal PT and Abnormal APTT
You repeat tests with a 50:50 mix
What should you test for if the 50:50 mix is NORMAL?

A

Test for factor deficiencies , so there might be an isolated deficiencies of one ‘thing; in a common pathway eg Factors V,X prothrombin or fibrinogen
or
Multiple factor deficiencies (common) eg liver disease, vit K def, warfarin, DIC

66
Q

66.Patient X, has an Normal PT and Normal APTT
You repeat tests with a 50:50 mix
What should you test for if the 50:50 mix is NORMAL?

A
  • Von Willebrand’s disease
  • Platelet Disorder
  • FXII Deficiency
  • Non-coagulation defect eg vascular disorder
67
Q

67.Patient X, has an Normal PT and Normal APTT
You repeat tests with a 50:50 mix
What should you test for if the 50:50 mix is ABNORMAL?

A
  • Dysfibrinogenaemia
  • Abnormal Fibrinolysis eg alpha 2 anti plasma def
  • Elevated FDPs (fibrin degradation products)
68
Q

68.Patient X, has an Normal PT and Abnormal APTT
You repeat tests with a 50:50 mix
What should you test for if the 50:50 mix is ABNORMAL?

A

You would test for inhibitor activity eg
Specific ones like Factors V,X,II and I - which are rare
or
Non-Specific like anti-phospholipid which is more common

69
Q

69.Patient X, has an Normal PT and Abnormal APTT
You repeat tests with a 50:50 mix
What should you test for if the 50:50 mix is NORMAL?

A

Test for factor deficiency :
-Isolated deficiency in intrinsic pathway (factors VIII,IX and XI)
or
-Multiple Factor deficiencies (rare)

70
Q

70.Patient X, has an Abnormal PT and Normal APTT
You repeat tests with a 50:50 mix
What should you test for if the 50:50 mix is NORMAL?

A

Test for factor deficiencies :
-Isolated deficiency of factor VII (rare)
or
Multiple factor deficiencies (common) eg liver disease, vit K def, warfarin, DIC

71
Q

71..Patient X, has an Abnormal PT and Normal APTT
You repeat tests with a 50:50 mix
What should you test for if the 50:50 mix is ABNORMAL?

A

You would test for inhibitor activity eg
-Specific ones like Factors VII - which are rare
or
Non-Specific like anti-phospholipid which is also rare

72
Q
  1. What is D Dimer?
A

a fibrin degradation product

73
Q
  1. When would D Dimer be elevated?
A

o It is found elevated in the situation of enhanced fibrinolysis (Thrombosis, Disseminated Intravascular Coagulation)
o Not specific for thrombosis also elevated as an acute phase reactant

74
Q
  1. What is a negative result of D Dimer useful for?
A

o A Negative result is useful if clinical suspicion of Venous Thromboembolism (VTE) is low.

Haematology (8 decks)

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