Haematology 3: Haemostasis And Bleeding Disorders Flashcards

1
Q

List 4 Pro-coagulant factors in the body?

A

Platelets
vWF
Endothelium
Coagulation cascade

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2
Q

List 4 Anti-coagulant factors in the body ?

A

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

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3
Q

List 2 thrombopoietic factors ?

A

Thrombopoietin
IL-6
IL-12

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4
Q

Which Surface glycoprotein do platelets use to bind to vWF ?

A

GpIb

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5
Q

Which glycoprotein do platelets use to bind directly to collagen ?

A

GpIa

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6
Q

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

A

GpIIb/IIIa

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7
Q

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

A

ADP

Thromboxane A2

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8
Q

How does Aspirin inhibit platelet aggregation?

A

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

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9
Q

List 2 drug targets for inhibiting platelet aggregation ?

A

Thromboxane A2 production - Aspirin

ADP receptors - Clopidogrel

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10
Q

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

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

A

B) extrinsic pathway

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11
Q

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

A

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

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12
Q

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

A

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

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13
Q

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

A

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

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14
Q

Which 4 clotting factors are vitamin K dependent ?

A

10
9
7
2

Think 1972

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15
Q

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

A
  • Converts plasminogen to plasmin
  • Plasmin cleaves The fibrin clot

tPA is produced by the endothelium

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16
Q

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

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

E) PAI1

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

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17
Q

What does TAFI do ?

A

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

18
Q

Deficiency of which component is the most Thrombogenic ?

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

C) AT3

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

19
Q

What is the role of Protein C and protein S ?

A

Inhibit FVIIIa and FVa

20
Q

What is the role of Thrombomodulin ?

A

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)

21
Q

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

A

APC inactivates FVa and FVIIIa

Requires protein S as cofactor

22
Q

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

A

People with Factor V Leiden have APC resistance.

This means activated factor V is not inactivated by APC.

23
Q

What is the physiological role of TFPI as an anticoagulant ?

A

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)

24
Q

What disease is associated with large platelets ?

A

grey platelet syndrome

25
What is ITP (immune thrombocytopenia purpura) ?
Autoantibodies against platelets | This causes the platelets to b e removed and destroyed by the immune system
26
List 2 common inherited disorders of coagulation (bleeding disorders) ?
Haemophilia A / B | Von willibrand disease
27
Which coagulation factors are deficient in: Haemophilia A Haemophilia B
Haemophilia A - Factor 8 | Haemophilia B - Factor 9
28
What is the inheritance pattern of haemophilia A /B ?
X-linked
29
What happens to APTT and PT in Haemophilia A/B ?
APTT - INCREASED PT- normal APTT Is a measure of the intrinsic pathway
30
List 3 clinical features of haemophilia A/B ?
Haemarthroses (bleeding into joints) Prolonged bleeding after surgery Ecchymoses
31
How is vWD inherited ?
Autosomal dominant
32
What are the differences in type1, type 2 and type 3 vWD ?
Type 1- partial quantitative defficiency in vWF Type 2- Partial Qualitative decency in vWF Type 3- Complete quantitative deficiency in vWF
33
How does most of vWF circulate in the blood ?
Most of it is bound to factor 8
34
What happens to APTT, PT, TT and fibrinogen in DIC ?
APTT- prolonged PT- prolonged TT- prolonged Fibrinogen- decreased
35
What are 3 treatments of Vitamin K deficiency ?
I.V Vitamin K FFP PCC (Prothrombin complex concentrate) Vit K dependent coagulation factors
36
List 3 differences in clinical presentation of Coagulation and platelet disorders ?
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
37
List 2 congenital causes of Vascular defects of coagulation ?
Older-Weber-rendu syndrome | Ehler’s danlos syndrome
38
List 3 acquired vascular defects of coagulation ?
Dengue haemorrhagic fever Scurvy Meningococcal infection
39
What is the treatment of Haemophilia A / B ?
Factor 8 / 9 concentrates replacement therapy
40
Which drug is used in the treatment of Haemophilia A ?
Desmopressin (causers increased vWF release from the endothelium. vWF is a factor VIII carrier)
41
Name 1 carrier protein of Factor VIII ?
vWF
42
Describe how you can used Ristocetin to test for vWD ?
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).