Disorders Of Blood Coagulation

Question 1

Why is blood clotting a good thing?

Answer 1

Stops bleeding at the site of injury

Keeps blood in and pathogens out

Question 2

What activates clotting?

Answer 2

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

Question 3

What is involved in primary haemostasis?

Answer 3

Platelet adhesion, aggregation, activation

Question 4

What is involved in secondary haemostasis?

Answer 4

Activation of fibrin formation through the clotting cascade

Question 5

What happens in primary haemostasis?

Answer 5

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

Question 6

What happens in secondary haemostasis?

Answer 6

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

Question 7

What does the tenase complex do?

Answer 7

Accelerate production of factor Xa

Question 8

What does the prothrombinase complex do?

Answer 8

Activate thrombin

Question 9

What happens in fibrinolysis?

Answer 9

Plasminogen -> plasmin by tissue plasminogen activator

Plasmin then degrades the fibrin mesh -> fibrin degredation products

Question 10

What is an example of fibrin degredation products?

Answer 10

D-dimer

Question 11

Where is tissue plasminogen activator found?

Answer 11

Endothelial cells

Question 12

What does antithrombin inhibit?

Answer 12

Serine protease

Question 13

What is antithrombin activity enhanced by?

Answer 13

Binding heparan binding sites on endothelial cells

Question 14

What does antithrombin inhibit?

Answer 14

Coagulation - thrombin, IXa and Xa

Question 15

What is heparan binding domain?

Answer 15

Basis of the anticoagulant activity of heparin

Question 16

What does heparin do?

Answer 16

Increases the activity of ATIII

Question 17

What are protein C and S?

Answer 17

Natural anticoagulant plasma proteins

Question 18

What is protein C activated by?

Answer 18

Thrombin bound to thrombomodulin on endothelial cells

Question 19

What is protein S?

Answer 19

APC cofactor which helps with binding to cell surfaces

Question 20

What does APC do?

Answer 20

Degrades cofactors FVa and FVIIIa

Question 21

What are three blood clotting disorders?

Answer 21

Haemophilia
Thrombophilia
Disseminated intravascular coagulation

Question 22

What are haemophilia A and B?

Answer 22

Mutations in coagulation factors

Question 23

What is von willebrand disease?

Answer 23

Platelet disorder

Question 24

What do collagen abnormalities cause?

Answer 24

Fragile blood vessels and bruising

Question 25

What is haemophilia?

Answer 25

Failure to clot -> haemorrhage

Question 26

What is thrombophilia?

Answer 26

Excessive clotting -> thrombosis

Question 27

What causes inherited thrombophilia?

Answer 27

Mutations in coagulation factors

Question 28

What causes acquired thrombophilia?

Answer 28

Malignancy increases clotting factors

Question 29

What is disseminated intravascular coagulation?

Answer 29

Whole body clots

Question 30

What causes haemophilia A?

Answer 30

Mutated FVIII

Question 31

What causes haemophilia B?

Answer 31

Mutated FIX

Question 32

What does haemophilia look like clinically?

Answer 32

Bleeding into joints

Question 33

What does von willebrand disease look like clinically?

Answer 33

Bleeding in the mucous membrane

Question 34

What happens when there is a factor V leiden mutation?

Answer 34

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

Question 35

What happens in an antithrombin deficiency?

Answer 35

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

Question 36

What are some causes of excessive clotting?

Answer 36

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

Question 37

What does DVT development depend on?

Answer 37

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

Question 38

What are the symptoms of DVT?

Answer 38

``` Pain and tenderness of veins Limb swelling Superficial venous distension Increased skin temperature Skin discolouration ```

Question 39

What are the risks with DVT?

Answer 39

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

Question 40

What is disseminated intravascular coagulation seen in?

Answer 40

Sepsis

Question 41

What happens in disseminated intravascular coagulation?

Answer 41

Depletion of clotting factors and platelets leading to bleeding

Question 42

What do anticoagulants do?

Answer 42

Prevent more clotting

Question 43

What do thrombolytics/ fibrinolytics do?

Answer 43

Reverse clotting

Question 44

Give some examples of anticoagulants

Answer 44

Warfarin Heparin Direct oral anticoagulants (DOACs)

Question 45

Give examples of thrombolytics/fibrinolytics

Answer 45

Plasminogen activators : EPA, streptokinase

Question 46

What does VTE stand for?

Answer 46

Venous thrombus embolism

Question 47

What pre-treatment investigations can you give for VTE?

Answer 47

Clotting screen FBC Renal screen Liver function tests

Question 48

What does the clotting screen show?

Answer 48

Prothrombin time Partial thromboplastin time Thrombin time

Question 49

What are the treatments for DVT?

Answer 49

Anticoagulants

Question 50

What are examples of DOACs?

Answer 50

Rivaroxaban and apixaban Dabigatran

Question 51

What are some bleeding complications from anticoagulants?

Answer 51

Anything from nosebleed -> intercranial haemorrhage