Haematology 3 - Coagulation

Question 1

Recall 4 endogenous anti-coagulants

Answer 1

Anti-thrombin
TFPI
Protein C
Protein S

Question 2

Recalll 1 procoagulant factors and 3 anticoagulant factor that are synthesised in vascular endothelium

Answer 2

vWF

PGI2
Plasminogen activators (important proteins for activating fibrinolysis)
Thrombomodulin (receptor that is essential for proteinC/S pathway)

Question 3

Recall the 2 possible mechanisms of platelet activation

Answer 3

1. vWF binds to Gp1b which binds to platelets to activate them
2. Endothelial Gp1a binds directly to the platelet to activate

Question 4

Via which receptors do platelets adhere to each other, and what is needed for this to happen?

Answer 4

GpIIb/IIIa using fibrinogen and calcium

Question 5

Recall one inducer and one inhibitor of platelet aggregation, and the enzyme required for the synthesis of both

Answer 5

Thromboxane A2 increases aggregation
PGI2 inhibits platelet aggregation
COX enzyme

Question 6

Why does aspirin have an anticoagulant effect?

Answer 6

Irreversibly iInhibits COX enzyme which is necessary for thromboxane A2 production

Question 7

What is the rate-limiting step in fibrin formation?

Answer 7

Factor Xa

Question 8

Which clotting factors are vitamin K dependent?

Answer 8

II, VII, IX and X

Question 9

How does vitamin K activate clotting factors?

Answer 9

Vit K is the co-factor for the gamma decarboxylation of the clotting factors (produced in liver)

Question 10

Recall 4 factors that promote fibrinolysis

Answer 10

Factor IXa, Xa, TPA and urokinase

These all increase plasmin production which cleaves fibrin

Question 11

What is the role of plasmin?

Answer 11

Breaks down fibrin in fibriolysis

Question 12

What is the mechanism of action of heparin?

Answer 12

Augments anti-thrombin effect

Question 13

What is the role of proteins C and S?

Answer 13

Inactivate Factors 5 and 8

Question 14

What are the roles of tissue factor and TFPI

Answer 14

Tissue factor activates factor Xa

TFPI neutralises tissue factor

Question 15

How can platelet and coagulation factor disorders be distinguisghed clinically?

Answer 15

Platelet problems –> immediate superficial bleeding

Coagulation factor deficiencies –> delayed, deep bleeding and haemarthroses

Question 16

Recall 4 possible causes of ITP

Answer 16

Vancomycin
SLE
Sarcoidosis
Lymphoproliferative disease

Question 17

Why does DIC cause thrombocytopaenia?

Answer 17

Increased utilisation

Question 18

How does the presentation of auto-immune thrombocytopaenia differ between children and adults?

Answer 18

In children it tends to be acute whereas it is chronic in adults

Question 19

How should autoimmune ITP be treated?

Answer 19

Steroids
IV Ig (to compete with auto-antibody)

Question 20

What is the expected APTT and PT results in haemophilia?

Answer 20

APTT prolonged

Normal PT

Question 21

What is the inheritance pattern of von willebrand disease?

Answer 21

Autosomal dominant

Question 22

What are the 3 different types of von willebrand disease?

Answer 22

Type 1: partial quantitative deficiency (aut dom)
Type 2: qualitative deficiency (aut dom)
Type 3: complete quantitative deficiency (aut rec)- very similar to haemophilia A because binding of factor8 and vWF protects factor8 from destruction in circulation

Question 23

Recall some causes of DIC

Answer 23

Sepsis
Trauma
Cancer
Obstetric complications
Vascular disorders
Reaction to a toxin

Question 24

What is DIC?

Answer 24

Activation of both coagulation and fibrinolysis causing both thrombosis and bleeding

Question 25

What is the antidote to heparin?

Answer 25

Protamine sulphate