Haematology 3: Haemostasis And Bleeding Disorders

Question 1

List 4 Pro-coagulant factors in the body?

Answer 1

Platelets
vWF
Endothelium
Coagulation cascade

Question 2

List 4 Anti-coagulant factors in the body ?

Answer 2

AT (antithrombin)
Protein S + Protein C
TFPI (Tissue factor pathway inhibitor)
Fibrinolysis

Question 3

List 2 thrombopoietic factors ?

Answer 3

Thrombopoietin
IL-6
IL-12

Question 4

Which Surface glycoprotein do platelets use to bind to vWF ?

Answer 4

GpIb

Question 5

Which glycoprotein do platelets use to bind directly to collagen ?

Answer 5

GpIa

Question 6

Which glycoproteins do platelets use to bind to other platelets when aggregating ?

Answer 6

GpIIb/IIIa

Question 7

Which 2 mediators do platelets release when they bind to subendothelial structures (vWF or collagen) to cause platelet aggregation ?

Answer 7

ADP

Thromboxane A2

Question 8

How does Aspirin inhibit platelet aggregation?

Answer 8

aspiring irreversibly Inhibits Cyclo-oxygenase (COX)
This prevents Arachidonic acid being converted to endoperoxides
This prevents formation of thromboxane A2
Less Thromboxane A2 means less platelet aggregation

Question 9

List 2 drug targets for inhibiting platelet aggregation ?

Answer 9

Thromboxane A2 production - Aspirin

ADP receptors - Clopidogrel

Question 10

Which pathway is more important for coagulation in the human body ?

A) Intrinsic pathway
B) Extrinsic pathway
C) Contact activation pathway

Answer 10

B) extrinsic pathway

Question 11

Describe the sequence of events in the Initiation phase of the Clotting cascade ?

Answer 11

1) Damage to endothelium causes TF to be exposed
2) Factor VII binds to TF and becomes activated to FVIIa
3) FVIIa/TF complex activate FIX and FX to FIXa and FXa
4) FXa binds to FVa

Question 12

Describe the sequence of events in the activation phase of the clotting cascade ?

Answer 12

1) FXa/FVa complex converts prothrombin to thrombin
2) Thrombin activates FVIII, FXI and recruits more FVa
3) FXIa activates FIX to FIXa
4) Activated platelet binds FVa, FVIIIa and FIXa

Question 13

Describe the sequence of events in the propagation phase of the clotting cascade ?

Answer 13

1) FVIIIa/ FIXa complex on platelets activates FXa on the surface of the platelet.
2) FXa and FVa cause a “thrombin burst” where loads of Prothrombin is converted to Thrombin
3) Thrombin converts fibrinogen to fibrin
4) Fibrin is cross linked to form a stable fibrin clot

Question 14

Which 4 clotting factors are vitamin K dependent ?

Answer 14

10
9
7
2

Think 1972

Question 15

What is the role of tPA (tissue plasminogen activator) ?

Answer 15

• Converts plasminogen to plasmin
• Plasmin cleaves The fibrin clot

tPA is produced by the endothelium

Question 16

Which of these molecules does not promote Plasminogen conversion to Plasmin ?

A) tPA
B) Urokinase 
C) FXIIa
D) FXIa 
E) PAI 1

Answer 16

E) PAI1

Plasminogen activator inhibitor inhibits Plasminogen conversion to Plasmin by inhibiting Urokinase and tPA

Question 17

What does TAFI do ?

Answer 17

TAFI (thrombin Activated Fibrinolysis inhibitor) is a Thrombin dependent inhibitor of Fibrin breakdown

Question 18

Deficiency of which component is the most Thrombogenic ?

A) TAFI
B) FVIIIa
C) AT3
D) vWF 
E) Protein S

Answer 18

C) AT3

Deficiency of Antithrombin (AT) is very rare but is the most thrombogenic

Question 19

What is the role of Protein C and protein S ?

Answer 19

Inhibit FVIIIa and FVa

Question 20

What is the role of Thrombomodulin ?

Answer 20

Thrombomodulin is an endothelial receptor for Protein C
It first needs to be activated by Thrombin.
EPCR is another receptor which helps Thrombomodulin bind to protein C

When Thrombomodulin binds to Thrombin and Protein C the complex is called APC (activated protein C)

Question 21

What is the role of APC (activated protein C) ?

Answer 21

APC inactivates FVa and FVIIIa

Requires protein S as cofactor

Question 22

What is different in the interaction between APC and FVa in people with Factor V Leiden ?

Answer 22

People with Factor V Leiden have APC resistance.

This means activated factor V is not inactivated by APC.

Question 23

What is the physiological role of TFPI as an anticoagulant ?

Answer 23

TFPI neutralises the TF/FVIIa complex.

TFPI is produced as a result of TF/FVIIa complex formation in order to stop activation by the extrinsic pathway. (TF/FVIIa is only required for a very short time to activate FX and FIX)

Question 24

What disease is associated with large platelets ?

Answer 24

grey platelet syndrome

Question 25

What is ITP (immune thrombocytopenia purpura) ?

Answer 25

Autoantibodies against platelets

This causes the platelets to b e removed and destroyed by the immune system

Question 26

List 2 common inherited disorders of coagulation (bleeding disorders) ?

Answer 26

Haemophilia A / B

Von willibrand disease

Question 27

Which coagulation factors are deficient in:

Haemophilia A
Haemophilia B

Answer 27

Haemophilia A - Factor 8

Haemophilia B - Factor 9

Question 28

What is the inheritance pattern of haemophilia A /B ?

Answer 28

X-linked

Question 29

What happens to APTT and PT in Haemophilia A/B ?

Answer 29

APTT - INCREASED
PT- normal

APTT Is a measure of the intrinsic pathway

Question 30

List 3 clinical features of haemophilia A/B ?

Answer 30

Haemarthroses (bleeding into joints)
Prolonged bleeding after surgery
Ecchymoses

Question 31

How is vWD inherited ?

Answer 31

Autosomal dominant

Question 32

What are the differences in type1, type 2 and type 3 vWD ?

Answer 32

Type 1- partial quantitative defficiency in vWF
Type 2- Partial Qualitative decency in vWF
Type 3- Complete quantitative deficiency in vWF

Question 33

How does most of vWF circulate in the blood ?

Answer 33

Most of it is bound to factor 8

Question 34

What happens to APTT, PT, TT and fibrinogen in DIC ?

Answer 34

APTT- prolonged
PT- prolonged
TT- prolonged
Fibrinogen- decreased

Question 35

What are 3 treatments of Vitamin K deficiency ?

Answer 35

I.V Vitamin K
FFP
PCC (Prothrombin complex concentrate) Vit K dependent coagulation factors

Question 36

List 3 differences in clinical presentation of Coagulation and platelet disorders ?

Answer 36

Platelet disorders

• Superficial bleeding (petechia)
• mucous membrane bleeding
• bleeding immediately after surgery

Coagulation disorders

• Deep bleeding into Joints (haemarthroses)/muscles
• delayed bleeding after surgery/trauma
• no prolonged bleeding after cuts

Question 37

List 2 congenital causes of Vascular defects of coagulation ?

Answer 37

Older-Weber-rendu syndrome

Ehler’s danlos syndrome

Question 38

List 3 acquired vascular defects of coagulation ?

Answer 38

Dengue haemorrhagic fever
Scurvy
Meningococcal infection

Question 39

What is the treatment of Haemophilia A / B ?

Answer 39

Factor 8 / 9 concentrates replacement therapy

Question 40

Which drug is used in the treatment of Haemophilia A ?

Answer 40

Desmopressin (causers increased vWF release from the endothelium. vWF is a factor VIII carrier)

Question 41

Name 1 carrier protein of Factor VIII ?

Answer 41

vWF

Question 42

Describe how you can used Ristocetin to test for vWD ?

Answer 42

Add Ristocetin to the patients vWF and platelets in a test tube. Ristocetin normally causes vWF to find to Gp1b on platelets causing platelet aggregation. If there is no platelet aggregation then this means there is a qualitative defect in vWF or Gp1b (Bernard soulier syndrome).