Haemostasis

Question 1

What is haemostasis?

Answer 1

The arrest of bleeding with the maintenance of vascular patency

Question 2

What are the requirements for well functioning haemostasis?

Answer 2

Permanent state of readiness
Prompt response
Localised response
Protection against unwanted thrombosis

Question 3

What is primary haemostasis?

Answer 3

Formation of platelet plug

Question 4

What is secondary haemostasis?

Answer 4

Formation of fibrin clot

Question 5

What are the components of normal haemostasis?

Answer 5

Primary haemostasis; platelet plug
Secondary haemostasis; fibrin clot
Fibrinolysis
Anticoagulant defences

Question 6

How are platelets formed?

Answer 6

Budding of megakaryocytes in bone marrow

Question 7

What is the life span of a platelet?

Answer 7

7-10 days

Question 8

Do platelets have a nucleus?

Answer 8

No

Question 9

How does platelet adhesion occur?

Answer 9

Endothelial damage exposes collagen and releases von Willebrand factor (VWF) which results in platelet adhesion at the site of injury

Question 10

How do platelets know where the site of injury is?

Answer 10

Once initial platelet adhesion has occurred, degranulation occurs leading to aggregation of platelets

Question 11

What can cause failure of platelet plug formation?

Answer 11

Vascular; scurvy, old age
Thrombocytopenia
Reduced function; antiplatelets
VWF

Question 12

What are the consequences of failure of primary haemostasis?

Answer 12

Spontaneous bruising and purpura
Mucosal bleeding; epistaxis, GI, conjunctival, MENORRHAGIA
Severe; intracranial haemorrhage, retinal haemorrhage

Question 13

What is the screening test for primary haemostasis?

Answer 13

Platelet count

In VWF; there will be decreased platelets and a low factor 8 (prolonged APTT)

Question 14

Descibe the mechanism of fibrin clot formation

Answer 14

Tissue Factor binds with factor 7a (initiation)
This leads to the activation of factors 5 and 10a.
Factors 5 and 10a will result in the cleavage of prothrombin (2) to thrombin (2a)
Thrombin results in the cleavage of fibrinogen to fibrin
Thrombin will also act to activate factors 8 and 9 (amplification)
Which will act to further increase factors 5 and 10a (propagation) to increase thrombin levels
Formation of a stable fibrin clot

Question 15

What is initiation in fibrin clot formation?

Answer 15

Activation of tissue factor and clotting factor 7a

Question 16

What is amplification in fibrin clot formation?

Answer 16

Thrombin acts to activate clotting factors 8 and 9

Question 17

What is propagation in fibrin clot formation?

Answer 17

Activated clotting factors 8 and 9 act on 5 and 10a to increase thrombin levels via cleavage of prothrombin

Question 18

What can cause failure of fibrin clot formation?

Answer 18

Single clotting factor deficiency; haemophilia
Multiple clotting factor deficiencies; DIC
Increased fibrinolysis

Question 19

What is haemophilia A (more common)?

Answer 19

Deficiency of clotting factor 8

Question 20

What is haemophilia B?

Answer 20

Deficiency of clotting factor 9a

Question 21

Describe fibrinolysis

Answer 21

Plasmin is formed from plasminogen via tPA

Plasmin will act on fibrin to break it down into FDPs

Question 22

How are FDPs measured?

Answer 22

D-dimer

Indication of excess fibrinolysis; DIC and DVT/PE

Question 23

Is there a clinical syndrome for failure of secondary haemostasis?

Answer 23

No

If haemophilia; bleeding into joints (haemarthrosis) and muscles

Question 24

What are the screening tests for fibrin clot formation?

Answer 24

Prothrombin time

Activated Partial Thromboplastin Time (APTT)

Question 25

What does prothrombin time assess?

Answer 25

Extrinsic Pathway Add tissue factor and phospholipid thromboplastin) to patients serum to activate factor 7a Measures factor 7a, 5, 10a and prothrombin

Question 26

What does APTT assess?

Answer 26

Intrinsic Pathway Clotting factors 8 and 9a And 5, 10a and prothrombin

Question 27

What will increase prothrombin time?

Answer 27

Deficiency in factor 7

Question 28

What will increased APTT time?

Answer 28

Deficiency in factors 8 or 9a (haemophilia)

Question 29

What will increase both prothrombin and APTT?

Answer 29

Deficiency in 5, 10a, prothrombin, fibrinogen or both 8/9a and 7 Multiple clotting factor deficiency or the main pathway that links both (5, 10a, prothrombin, fibrinogen)

Question 30

What is the clinical approach to bleeding disorders?

Answer 30

History; bleeding, bruising, duration(? life-long) Previous surgery/ dental extractions Drug hx FMHx Exam; fundal haemorrhages, mouth, purpura (primary haemostasis), muscles and joints (secondary haemostasis), splenomegaly

Question 31

What is the action of anti-thrombin?

Answer 31

Serine protease inhibitor Naturally occuring anti-coag Deactivates TF/7a, 5/10a and 8/9a along with thrombin inactivation

Question 32

What drug acts to increase anti-thrombin action?

Answer 32

Heparin

Question 33

What is the action of protein C and S?

Answer 33

Act to deactivate 5/10a and 8/9a | Thrombin will also bind to thrombomodulin to have a positive feedback to increase levels of protein C and S

Question 34

What is thrombophilia?

Answer 34

Deficiency of naturally occuring anticoagulants | Tendency to develop DVT/ PE

Question 35

In primary haemostasis; what will activated platelets release and what is the result of that?

Answer 35

``` Thromboxane A2 (TXA2) Acts to release serotonin and ADP which will result in platelet aggregation and vasoconstriction ```

Question 36

What component of the platelet cell membrane allows for adhesion?

Answer 36

Pseudopodia

Question 37

What role does ADP specifically have in primary haemostasis?

Answer 37

Aggregation to form soft plug | Expose acidic phospholipids on platelet surface to initiate coagulation and solid clot formation

Question 38

What is virchows triad?

Answer 38

Injury to vessel wall Abnormal blood flow Increased coagulability of blood

Question 39

Describe an arterial thrombus

Answer 39

White; mainly platelets in a fibrin mesh Forms an embolus ANTIPLATELET THERAPY

Question 40

Describe a venous thrombus?

Answer 40

White head, jelly like red tail, fibrin rich | ANTICOAG THERAPY