Haematology 3 - Coagulation

Question 1

Recall 4 endogenous anti-coagulants

Answer 1

Anti-thrombin
TFPI
Protein C
Protein S

Question 2

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

Answer 2

PGI2
vWF
Plasminogen activators
Thrombomodulin (anticoagulant)

Question 3

Recall the 2 possible mechanisms of platelet activation

Answer 3

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

Question 4

Via which receptors to 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

Inhibits 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 (made in liver)

Question 9

How does vitamin K activate clotting factors?

Answer 9

vitamin K is required as a co-enzyme for the gamma-carboxylation of the clotting factors

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 fibrinolysis

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: low levels
Type 2: deficiency in function
Type 3: absent VWF

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

consumption of clotting factors and fibrin, resulting in uncontrollable bleeding

Question 25

What is the antidote to heparin?

Answer 25

Protamine sulphate

Question 26

outline the blood test results of DIC

Answer 26

elevated INR, APTT, PT, D Dimer and Bleeding time. | decrease in platelet count, fibrinogen and clotting factor levels.

Question 27

What description is given to red blood cells which are typically polychromatic and stain heavily for the presence of RNA?

Answer 27

reticulocyte

Question 28

what is heparin induced thrombocytopenia?

Answer 28

thrombocytopenia caused by antibodies directed against heparin AND platelet factor 4. despite the low platelets it is a prothrombotic condition.

Question 29

function of thrombomodulin

Answer 29

leads to activation of Protein C

Question 30

what's the difference between aspirin and NSAIDs in terms of mechanism

Answer 30

aspirin irreversibly inhibit COX NSAIDs inhibit reversibly in the archidonic acid pathway

Question 31

4 effects of thrombin

Answer 31

o Activates fibrinogen o Activates platelets o Activates pro-cofactors (Factor 5 and Factor 8) o Activates zymogens (Factor 7, 11 and 13)

Question 32

how does bile affect vitamin K

Answer 32

Vitamin K is fat soluble so need bile to absorb vitamin K (i.e. bile duct obstruction causes deficiency)

Question 33

how do bacteria affect vitamin K

Answer 33

bacteria help make Vit K so, antibiotics can harm gut flora reaching Vit K absorption

Question 34

most common cause of vitamin A deficiency

Answer 34

warfarin

Question 35

2 inhibitors of plasmin

Answer 35

Alpha-2 antiplasmin | Alpha-2 macroglobulin

Question 36

give 2 distinct roles of thrombin

Answer 36

as a procoagulant when it converts fibrinogen into an insoluble fibrin clot thrombin activates protein C, it acts as an anticoagulant.

Question 37

how many antithrombins are there? which is most potent

Answer 37

five in total | most potent = AT 3 potentiator = heparin

Question 38

what is the most thrombogenic condition

Answer 38

lack or deficiency of antithrombin

Question 39

state 3 physiological anticoagulants & their mechanisms

Answer 39

antithrombin - Inhibits thrombin, protein C & S - inactivates F5a and F8a tissue factor pathway inhibitor - inactivates 7a

Question 40

drug to reduce warfare overdose

Answer 40

PCC | prothrombinase complex concentrate (contains vit K dep clottting factors)