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CARDIORESPIRATORY 2 > HAEMOSTASIS AND THROMBOSIS > Flashcards

HAEMOSTASIS AND THROMBOSIS Flashcards

1
Q

What is primary and secondary haemostasis?

A

Primary: formation of unstable platelet plug (platelet adhesion and aggregation)

Secondary: Stabilisation of the plug with fibrin (blood coagulation)

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2
Q

What are the mechanisms of haemostasis in order?

A

Vessel constriction - limits blood flow
Primary haemostasis- limits blood loss + provides surface for coagulation
Secondary haemostasis - stops blood loss
Fibrinolysis - restores vessel integrity

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3
Q

How can the balance of haemostasis be tipped towards bleeding?

A

Increased fibrinolytic factors, anticoagulant proteins
Decreased coagulant factors, platelets

Could be lacking a coagulant factor due to failure of production or increased consumption/clearing
Could be defective function of a factor

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4
Q

Describe the process primary haemostasis

A

Platelet binding to VWF on endothelial cells with GPIb
Or
Direct platelet adhesion with GPIa to the collagen

This causes release of ADP, thromboxane and granular contents of platelet activating the platelets

This activates/flipflops the GPIIb/IIIa receptor which binds the platelet to fibrinogen
The fibrinogen links up multiple platelets forming the plug

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5
Q

What are the causes of disorder of primary haemostasis ?

A

Problem with platelets
Problem with VWF
Problem with vessel wall

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6
Q

What could cause problems with platelets?

A

Thrombocytopenia:

  • Bone marrow failure e.g. leukaemia, B12 def
  • Accelerated clearance e.g. auto ITP
  • Pooling and destruction in splenomegaly

Impaired function:

  • Hereditary absence of glycoproteins or storage granules
  • Acquired due to drugs e.g. aspirin, NSAIDs
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7
Q

What occurs in auto-immune thrombocytopenia Purpura (auto-ITP)?

A

Antiplatelet autoantibodies bind to sensitised platelet which is then phagocytoses my macrophages

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8
Q

Name 3 hereditary platelet defects and occurs

A

Glanzmann’s thromboasthenia - lack of GPIIa
Bernard Soulier syndrome - lack of GPIIb
Storage pool disease - problem with platelet granules

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9
Q

When is anti-platelet therapy used?

A

To prevent cardiovascular and cerebrovascular disease

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10
Q

How does aspirin work?

A

Irreversibly blocks cycle-oxygenase (COX) preventing downstream production of thromboxane A2 and thus platelet aggregation.

Downstream prostacyclin also inhibited but it is also made by endothelial cells so its ok

Effects ~7 days until most platelets been replaced

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11
Q

How does clopidogrel work?

A

Irreversibly blocks ADP receptor on platelets preventing platelet activation

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12
Q

What could cause problems with VWF?

A

Von Willebrand disease

  • Hereditary decrease of quantity + function
  • Acquired due to antibody (rare)
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13
Q

What are the functions of VWF in haemostasis?

A

Binding to collagen and capturing platelets
Stabilising factor VIII (coagulating)
- low VWF may cause low factor VIII

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14
Q

In type 1 and 3 VWD what is the effect on VWF?

A

Deficiency of VWF

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15
Q

In type 2 VWD what is the effect on VWF?

A

VWF with abnormal function

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16
Q

What could cause problems with the vessel wall?

A

Hereditary haemorrhage telangiectasia Ehlers-Danlos syndrome and other connective tissue disorders

Acquired:

  • Steroid therapy (atrophy of collagen)
  • Ageing (senile purpura) (atrophy of collagen)
  • Vasculitis
  • Scurvy (Vit C def causing defective collagen synthesis)
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17
Q

Describe how a fault primary haemostasis bleeding typically looks

A 
Immediate
Prolonged bleeding from cuts
Nose blees > 20 min
Gum bleeding prolonged
Menorrhagia
Bruising (ecchymosis)
Prolonged bleeding after trauma/surgery
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18
Q

What is the difference between petechiae, Purpura and ecchymosis?

A

All caused by bleeding under skin

Petechiae < 3mm
Purpura 3-10mm
Eccymosis (bruise) > 10mm

Purpura doesn’t blanch when pressure is applied

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19
Q

What are some tests you can carry out for primary haemostasis disorders?

A

Platelet count, platelet morphology
Bleeding time/PFA100 in lab (platelet function analysis)
Assays of VWF
Clinical observation

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20
Q

What would the results of a coagulation screen (prothrombin time, APTT) be in individuals with primary haemostasis disorders?

A

Normal except for more severe VWD cases where factor VIII is low

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21
Q

At what platelet count does severe spontaneous bleeding occur?

A

< 10 x 10^9/L

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22
Q

At what platelet count is spontaneous bleeding common?

A

< 40 x 10^9/L

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23
Q

At what platelet count does no spontaneous bleeding occur, but bleeding with trauma occur?

A

< 100 x 10^9/L

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24
Q

What is the normal range of platelet count?

A

100 x 10^9/L to 400 x 10^9/L

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25
Q

What are the treatments for failure of production/function in primary haemostasis?

A

Replace missing factor/platelets (prophylactic/therapeutic)

Stop drugs e.g. aspirin/NSAIDs

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26
Q

What are the treatments for destruction by immune system in primary haemostasis?

A

Immunosuppression e.g. prednisolone (steroids)

Splenectomy for ITP

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27
Q

What are the treatments for increased consumption in primary haemostasis?

A

Treat cause of abnormal coagulation

Replaces as necessary

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28
Q

What are some additional treatments for abnormal haemostasis?

A
  • Desmopressin (vasopressin analogue, releases endogenous stores of VWF so only useful in mild disorders)
  • Tranexamic acid (antifibrinolytic)
  • Fibrin glue/spray (during surgery)
  • Other approaches e.g. hormonal for menorrhagia
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29
Q

What is the role of coagulation in secondary haemostasis?

A

To generate thrombin (IIa) which converts fibrinogen to fibrin

30
Q

What are the disorders of coagulation which cause a deficiency of coagulation factor production?

A

Hereditary:

  • Haemophilia A (factor VIII)
  • Haemophilia B (factor IX)

Acquired

  • Liver disease/failure (only VWF and factor V aren’t synthesised in liver)
  • Anticoagulant drugs e.g. warfarin, DOACs
31
Q

What are the disorders of coagulation which cause a dilution of coagulation factor?

A

Blood transfusion (insufficient plasma given causing dilution)

32
Q

What are the disorders of coagulation which cause an increased consumption of coagulation factor?

A

Acquired:

  • Disseminated intravascular coagulation (DIC) - common
  • Immune autoantibodies - rare
33
Q

What is the genetics of haemophilia?

A 
Sex linked (1 in 10^4 births)
Others very rare
34
Q

What is haemophilia?

A

Genetic disease causing a failure to generate fibrin to stabilise platelet plug

35
Q

What is the hallmark of haemophilia?

A

Haemoarthrosis: spontaneous synovial lining joint bleeding causing significant joint deformity

Usually prophylactic factor replacement therapy should be started at ~ 9 months of age but in developing countries not that common

36
Q

Why should intramuscular injections be avoided in patients with haemophilia?

A

Causes extensive haematoma

37
Q

If a patient has an absence of factor VIII/IX (haemophilia) how bad is it and what occurs?

A

Severe but compatible with life

Spontaneous joint and muscle bleeding

38
Q

If a patient has an absence of factor II (prothrombin) how bad is it?

A

Lethal

39
Q

If a patient has an absence of factor XI how bad is it?

A

Bleed after trauma but not spontaneously

40
Q

If a patient has an absence of factor XII what occurs

A

No bleeding at all

41
Q

What is disseminated intravascular coagulation (DIC) and what are its affects?

A

Generalised activation of coagulation causing excessive consumption and depletion of coagulation factors.

Platelets are also consumed causing thrombocytopenia.

Activation of fibrinolysis depletes fibrinogen and raised D-dimer (breakdown product)

Deposition of fibrin in vessels causing organ failure

Associated with sepsis, major tissue damage and inflammation

42
Q

What are the clinical features of coagulation/secondary haemostasis disorders?

A

Superficial cuts don’t bleed
Bruising is common, nosebleeds rare
Spontaneous bleeding deep into muscles and joints
Bleeding after trauma may be delayed and is prolonged
Bleeding frequently restarts after stopping

43
Q

List the tests for coagulation disorders

A

Clotting screen:

  • Prothrombin time (PT)
  • Activated partial thromboplastin time (APTT)
  • Full blood count (platelets)

Coagulation factor assays
Tests for inhibitors

44
Q

Which pathway does the prothrombin time measure and thus which factors?

A

Extrinsic pathway
Tissue factor (III)
Factor VII

45
Q

Which pathway does the APTT measure and thus which factors?

A

Intrinsic pathway

Factors I, II, IX, X, XI, and XII

46
Q

If APTT is abnormal and PT normal what could be the cause?

A

Haemophilia

47
Q

If PT is abnormal and APTT normal what could be the cause?

A

Factor VII deficiency

48
Q

If both PT and APTT are abnormal what could be the cause?

A

Liver disease
Anticoagulant drugs
DIC
Dilution

49
Q

What are the different methods for replacing missing coagulation factors?

A

Fresh frozen plasma (all factors)
Cryoprecipitate (rich in fibrinogen, VWF, VIII, XIII)
Factor concentrates (available for all factors except V)
Recombinant forms of VIII and IX to treat bleeds or as prophylaxis to prevent bleeds

50
Q

What are some novel treatments for haemophilia?

A

Gene therapy (haem A/B)

Bispecific antibodies (heam A) - mimics procoagulant function of VIII

RNA silencing (haem A/B) - targets natural anticoagulant antithrombin

51
Q

What does pulmonary embolism (PE) present as?

A 
Tachycardia
Hypoxia
Shortness of breath
Chest pain
Haemopysis (coughing blood)
Sudden death
52
Q

What does deep vein thrombosis (DVT) present as?

A 
Painful leg
Swelling
Red
Warm
May embolism to lungs causing PE
Post thrombotic syndrome (long standing damage to valves causing long pain and swelling)
53
Q

What is Virchow’s triad?

A

Three contributory factors to thrombosis:

  • Blood (dominant in venous)
  • Vessel wall (dominant in arterial)
  • Blood flow (contributes in both)
54
Q

What is thrombophilia?

A

Increased risk of venous thrombosis

55
Q

How may thrombophilia present?

A

Thrombosis at young age
Spontaneous thrombosis
Multiple thromboses (recurrent)
Thrombosis whilst anti-coagulated

56
Q

How can the balance of haemostasis be tipped towards venous thrombosis?

A

Increase coagulant factors/platelets (VIII, II, V Leiden)

Decrease in fibrinolytic factors, anticoagulant proteins (antithrombin, protein C, protein S)

57
Q

Why might coagulant factors/platelets increase?

A

Myeloproliferative disorders increase platelets

Surgery, cancer or pregnancy can increase clotting factors

58
Q

Why might there be reductions in anticoagulant protein?

A

e.g. nephrotic syndrome where it leaks out

59
Q

How do protein C and protein S work?

A

Inactivates factor Va and VIIIa

60
Q

How does antithrombin work?

A

Inactivates thrombin, factor II and Va

61
Q

Give 3 examples of anticoagulant proteins

A

Antithrombin
Protein C
Protein S

62
Q

What factor increases risk of venous thrombosis?

A

Age

63
Q

What are some inherited thrombophilic traits which increase the risk of venous thrombosis?

A 
Anticoagulant deficiency (antithrombin, protein C/S)
Procoagulant excess (factor V leiden, factor VIII, prothrombin (II))
64
Q

How likely are patients with factor V Leiden develop venous thrombosis?

A

Usually won’t but if they do its with a combination of another event e.g. pregnancy

65
Q

What do we know about the role of the vessel wall in venous thrombosis?

A

Very little

66
Q

What causes the relationship between thrombosis and inflammation?

A

Many proteins active in coagulation are expressed on the surface of endothelial cells and their expression altered in inflammation

67
Q

What type of blood flow increases risk of thrombosis and when may this occur?

A

Reduced flow (stasis) e.g. in surgery, long haul flights and pregnancy

During pregnancy compression from foetus reduces blood flow

68
Q

Describe the causes of venous thrombosis

A

Multi-causal arising from interacting genetic and acquired risk factors

69
Q

How can venous thrombosis be prevented?

A

Asses and prevent risks

Prophylactic anticoagulant therapy

70
Q

How can risk of recurrence/extension of venous thrombosis be reduced?

A

Lower procoagulant factors e.g. warfarin, DOACs

Increase anticoagulant activity e.g. heparin to prevent a fresh clot from forming

CARDIORESPIRATORY 2 (8 decks)

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