Haemostasis

Question 1

What is haemostasis?

Answer 1

The process in which excessive blood loss in prevented at the site of a damaged vessel through activation of the clotting factors and platelets

Question 2

What does a platelet contain?

Answer 2

GPIb receptor
GPIIb/IIIa receptor
Glycogen for energy
Alpha granules 
Actin and myosin fibrils that enable the platelet to change shape

Question 3

What is in an alpha granule?

Answer 3

Clotting factors V, VIII, fibrinogen (I), vWF, and PDGF

Question 4

What are the sequences of events that occur within a damaged vessel?

Answer 4

Localised vasoconstriction by humoral factors —> Platelet adhesion to subendothelium —> Platelet activation and aggregation —> Activation of platelet cascade —> Fibrin formation —> Thrombus formation —> Fibrinolytic degradation of clot and vessel repair

Question 5

How does a damaged vessel cause platelet adhesion?

Answer 5

Collagen in the endothelium becomes exposed. Platelets adhere to the collagen through vWF and GPIb for tethering and rolling of the platelets. GPIIb/IIIa receptors then interact with vWF for a stronger bond.

Question 6

How does platelet aggregation occur?

Answer 6

Receptors interact with neighbouring platelets.

Question 7

What does the damaged endothelium produce?

Answer 7

ADP is released from the injured cell to activate metabolites in the platelets.

Question 8

What do platelets release in order to recruit more platelets?

Answer 8

Thromboxane A2.

Question 9

What do the platelets release for coagulation activation?

Answer 9

Dense and alpha granules released to activate the cascade for fibrin formation

Question 10

What does fibrin do?

Answer 10

Fibrin deposits over the platelets and traps RBCs to form a clot.

Question 11

What is the coagulation cascade?

Answer 11

Sequence of protein interactions that cause fibrin deposits.

Question 12

What is the function of the extrinsic pathway?

Answer 12

Initiates coagulation

Question 13

What is the function of the intrinsic pathway?

Answer 13

Amplifies the cascade

Question 14

What must be present in order for coagulation factors to be present?

Answer 14

Clotting factors must be bound to the -vely charged phospholipid surface of the disrupted membrane to form a binding site.

Question 15

Where are coagulation factors synthesised?

Answer 15

In the liver and travel in the circulation as inactive precursors.

Question 16

Which coagulation factors require fat soluble vitamin K?

Answer 16

Prothrombin, FVII, IX, X - activate to proteases

Question 17

What is FV a cofactor for?

Answer 17

FX

Question 18

What is FVIII a cofactor for?

Answer 18

FIX

Question 19

What is vWF?

Answer 19

Helps platelet aggregation and acts as a carrier protein for FVIII.

Question 20

Where is vWF synthesised?

Answer 20

Vessel endothelium and in megakaryocytes

Question 21

What happens in the extrinsic pathway?

Answer 21

FVIIa joins TF released from the damaged tissues, to initiate the sequence of events leading to Fibrin formation in the common pathway.

Question 22

What happens in the intrinsic pathway?

Answer 22

1) FXII converts to FXIIa on contact with the -vely charged surface of the membrane
2) XIIa activates XI
3) XI activates IX
4) IX combines with VIII, brought by vWF, to activate X
5) X activates to trigger the common pathway for fibrin formation

Question 23

What is the common pathway that leads to fibrin formation?

Answer 23

1) Xa combines with Va to convert Prothrombin into thrombin

2) Thrombin converts fibrinogen into fibrin

Question 24

What effect does thrombin have on its own production?

Answer 24

It has a +ve feedback to accelerate the production of acitvated XI, VIII and V and it causes the release of VIII from vWF

Question 25

What is the process of fibrinolysis once the bleeding resolves?

Answer 25

1) Thrombin induces release of tPA (tissue plasminogen activator) from the surrounding intact endothelium 2) Plasminogen binds into the clot 3) tPA converts plasminogen to plasmin 4) Plasmin protelyses fibrin into its products

Question 26

How are the fibrin products removed?

Answer 26

By the reticulo-endothelial system

Question 27

How does vessel repair occur?

Answer 27

PDGF causes smooth muscle and endothelial cells close to the injury to divide as the clot degrades.

Question 28

What is EPI?

Answer 28

An extrinisic pathway inhibitor - Inhibits direct activation of X by VIIa upon the formation of thrombin from the extrinsic pathway, to allow the intrinsic pathway to take over

Question 29

Why is control over the coagulation pathway needed?

Answer 29

To prevent coagulation at intact endothelium and to prevent thrombus formation.

Question 30

What are the anticoagulant proteins involved in the control of the pathway?

Answer 30

They neutralise activated coagulation factors: - Antithrombin III - Heparin - tPA and streptokinase - Protein C

Question 31

What are the anticoagulant functions of Antithrombin III?

Answer 31

Inactivates thrombin, IX, X, XI

Question 32

What are the anticoagulant functions of Heparin?

Answer 32

Enhances antithrombin acitivity and synthesis of prostacyclin, platelet inhibiting PG.

Question 33

What are the anticoagulant functions of tPA and steptokinase?

Answer 33

Activate conversion of plasminogen to plasmin.

Question 34

What are the anticoagulant functions of Protein C?

Answer 34

Thrombin binds to thrombomodulin on the intact cell membrane to allow protein C to bind. Once activated it forms a complex with Protein S and V to degrade Va and VIIIa to restrict the clot.

Question 35

Why is fat soluble Vit K needed for prothrombin, VII, IX and X?

Answer 35

Glutamic acid, O2 and CO2 form the alpha-carboxyglutamic acid component of these factors which requires reduced Vit K. Reduced Vit K is produced from Vit K by Vit K reductase

Question 36

What will inhibit Vit K reductase?

Answer 36

Warfarin is a reductase inhibitor that will prevent the cascade as there is no production of the coagulation factors.

Question 37

What is the complication of liver failure in regards to coagulation?

Answer 37

Reduced synthesis of the coagulation factors

Question 38

What is Bernard-Soulier syndrome?

Answer 38

A hereditary deficiency in GPIb.

Question 39

What is Glanzmann's thrombosthenia?

Answer 39

A hereditary deficiency in GPIIb/IIIa.

Question 40

What is thrombocytopenia?

Answer 40

A low platelet count due to AI or BM failure

Question 41

What do deficiencies of VIII and IX lead to?

Answer 41

Haemophilia A and B - hereditary clotting disorders

Question 42

Why may an acquired deficiency result?

Answer 42

Due to liver disease or Vit K deficiency

Question 43

What is thrombophilia?

Answer 43

An increased tendency to form clots. Hereditary: FV leiden mutation = resistance to protein C Protein C, S and antithrombin deficiences Hyperhomocysteinamiea (Increased AA) Acquired: Long haul flights, immobility, smoking, pregnancy, surgery, malignancy, myeloproliferative disorder, lupus

Question 44

What does prothrombin time detect?

Answer 44

Prolonged = VII deficiency (EXTRINSIC)

Question 45

What does activated partial thromboplastin time detect?

Answer 45

If APTT presents as prolonged the Pt's plasma is mixed with normal plasma. Normal time = clotting factor deficiency in INTRINSIC pathway Prolonged = inhibitor present e.g. VIII Ig, lupus anticoagulation

Question 46

What if both PT and APTT is prolonged?

Answer 46

Single deficiency in the COMMON pathway or multiple factors due to liver disease, vit K deficiency, warfarin treatment or DIC.

Question 47

What is DIC?

Answer 47

Disseminated intravascular coagulopathy causing uncontrolled response. Causes bleeding and thrombosis in microvascular structures resulting in death.