Disorders Of Blood Coagulation Flashcards

1
Q

Why is blood clotting a good thing?

A

Stops bleeding at the site of injury

Keeps blood in and pathogens out

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2
Q

What activates clotting?

A

Endothelium in blood vessels normally maintains an anticoagulant surface- when this is broken, collagen is exposed which activates clotting

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3
Q

What is involved in primary haemostasis?

A

Platelet adhesion, aggregation, activation

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4
Q

What is involved in secondary haemostasis?

A

Activation of fibrin formation through the clotting cascade

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5
Q

What happens in primary haemostasis?

A

If collagen becomes exposed to blood, von willebrand factors bind to it
Von willebrand factors bind to platelets from blood and activate them
Activated platelets express functional fibrinogen receptors

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6
Q

What happens in secondary haemostasis?

A

Tissue factor activates the coagulation cascade to initiate a minor burst of thrombin
Factor VIIa binds to tissue factor -> FXa -> conversion of prothrombin to thrombin
Thrombin activates receptors on platelets and endothelium -> inc in platelet aggregation and release of von willebrand factors
Thrombin also activates FVIIa and FVa which then form tenase complex and prothrombinase complex with platelets

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7
Q

What does the tenase complex do?

A

Accelerate production of factor Xa

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8
Q

What does the prothrombinase complex do?

A

Activate thrombin

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9
Q

What happens in fibrinolysis?

A

Plasminogen -> plasmin by tissue plasminogen activator

Plasmin then degrades the fibrin mesh -> fibrin degredation products

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10
Q

What is an example of fibrin degredation products?

A

D-dimer

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11
Q

Where is tissue plasminogen activator found?

A

Endothelial cells

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12
Q

What does antithrombin inhibit?

A

Serine protease

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13
Q

What is antithrombin activity enhanced by?

A

Binding heparan binding sites on endothelial cells

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14
Q

What does antithrombin inhibit?

A

Coagulation - thrombin, IXa and Xa

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15
Q

What is heparan binding domain?

A

Basis of the anticoagulant activity of heparin

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16
Q

What does heparin do?

A

Increases the activity of ATIII

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17
Q

What are protein C and S?

A

Natural anticoagulant plasma proteins

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18
Q

What is protein C activated by?

A

Thrombin bound to thrombomodulin on endothelial cells

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19
Q

What is protein S?

A

APC cofactor which helps with binding to cell surfaces

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20
Q

What does APC do?

A

Degrades cofactors FVa and FVIIIa

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21
Q

What are three blood clotting disorders?

A

Haemophilia
Thrombophilia
Disseminated intravascular coagulation

22
Q

What are haemophilia A and B?

A

Mutations in coagulation factors

23
Q

What is von willebrand disease?

A

Platelet disorder

24
Q

What do collagen abnormalities cause?

A

Fragile blood vessels and bruising

25
Q

What is haemophilia?

A

Failure to clot -> haemorrhage

26
Q

What is thrombophilia?

A

Excessive clotting -> thrombosis

27
Q

What causes inherited thrombophilia?

A

Mutations in coagulation factors

28
Q

What causes acquired thrombophilia?

A

Malignancy increases clotting factors

29
Q

What is disseminated intravascular coagulation?

A

Whole body clots

30
Q

What causes haemophilia A?

A

Mutated FVIII

31
Q

What causes haemophilia B?

A

Mutated FIX

32
Q

What does haemophilia look like clinically?

A

Bleeding into joints

33
Q

What does von willebrand disease look like clinically?

A

Bleeding in the mucous membrane

34
Q

What happens when there is a factor V leiden mutation?

A

Resistance to APC -> FVa not activated -> increased risk of DVT

35
Q

What happens in an antithrombin deficiency?

A

Thrombin, IXa and FXa are not inactivated -> increased risk of DVT

36
Q

What are some causes of excessive clotting?

A

Factor V leiden mutation
Antithrombin deficiency
Protein C deficiency
Protein S deficiency

37
Q

What does DVT development depend on?

A

Alterations in the blood constituents
Changes in normal blood flow
Damage to the endothelial layer

38
Q

What are the symptoms of DVT?

A
Pain and tenderness of veins
Limb swelling
Superficial venous distension
Increased skin temperature
Skin discolouration
39
Q

What are the risks with DVT?

A

If the clot is above the knee it is significantly more likely to embolise

40
Q

What is disseminated intravascular coagulation seen in?

A

Sepsis

41
Q

What happens in disseminated intravascular coagulation?

A

Depletion of clotting factors and platelets leading to bleeding

42
Q

What do anticoagulants do?

A

Prevent more clotting

43
Q

What do thrombolytics/ fibrinolytics do?

A

Reverse clotting

44
Q

Give some examples of anticoagulants

A

Warfarin
Heparin
Direct oral anticoagulants (DOACs)

45
Q

Give examples of thrombolytics/fibrinolytics

A

Plasminogen activators : EPA, streptokinase

46
Q

What does VTE stand for?

A

Venous thrombus embolism

47
Q

What pre-treatment investigations can you give for VTE?

A

Clotting screen
FBC
Renal screen
Liver function tests

48
Q

What does the clotting screen show?

A

Prothrombin time
Partial thromboplastin time
Thrombin time

49
Q

What are the treatments for DVT?

A

Anticoagulants

50
Q

What are examples of DOACs?

A

Rivaroxaban and apixaban

Dabigatran

51
Q

What are some bleeding complications from anticoagulants?

A

Anything from nosebleed -> intercranial haemorrhage