37 Heritable bleeding disorders

Question 1

What is the platelet receptor for fibrinogen?

What does it do?

Answer 1

Glycoprotein 2β3A.

Platelet activation.

Question 2

What is the platelet receptor for vWF?

What does it do?

Answer 2

Glycoprotein 1B9.

Platelet adhesion.

Question 3

How does aspirin act?

Answer 3

Inhibits COX enzymes, inhibiting the formation of thromboxane. Platelets don’t activate.

Question 4

How does clopidogrel act?

Answer 4

Inhibits ADP receptors on platelets, preventing platelet activation.

Question 5

How do GIIβ/IIIA antagonists act?

Answer 5

Inhibit fibrinogen binding to platelets.

Question 6

Which factors are involved in the intrinsic coagulation pathway? (4)

Answer 6

XII.
XI.
IX.
VII.

Question 7

What initiates the intrinsic coagulation pathway?

Answer 7

Foreign surface.

Question 8

Which factors are involved in the extrinsic clotting pathway? (2)

Answer 8

VII.

TF.

Question 9

Which factors are involved in the common coagulation pathway? (4)

Answer 9

X.
V.
II. Thrombin.
Fibrinogen. Fibrin.

Question 10

What does the APTT measure?

Answer 10

Intrinsic and common pathway function.

Question 11

What does the prothrombin time measure?

Answer 11

Extrinsic pathway function.

Question 12

What is the extrinsic pathway activated by?

Answer 12

Tissue factor exposure.

Question 13

Which anticoagulant factors circulate in the blood? (4)

Answer 13

Protein C.
Protein S.
Anti-thrombin III.
Fibrinolytic system.

Question 14

Explain the fibrinolytic system.

Answer 14

TPA breaks down plasminogen to plasmin. Plasmin breaks down fibrin.
α2-AP mops up plasmin, protecting clotting pathway.

Question 15

What are the four types of platelet and vessel wall defects?

Answer 15

Reduced platelet number.
Abnormal platelet function (aspirin).
Abnormal vessel wall (Ehlers-Danlos).
Abnormal platelet-wall interaction (vWD).

Question 16

Describe the type of bleeding typically seen in platelet/vascular defects. (4)

Answer 16

Petechiae.
Skin and mucous membranes.
Spontaneous.
Immediate and non-recurrent.

Question 17

Describe the type of bleeding seen in coagulation defects? (4)

Answer 17

Deep haematoma.
Haemarthrosis.
Retroperitoneal.
Prolonged and often recurrent.

Question 18

What are the three types of von Willebrand disease?

Answer 18

1. Decreased amount.
2. Normal amount of low molecular weight polymer.
3. Absent molecule.

Question 19

Which coagulation factor acts as a carrier protein for von Willebrand factor?

Answer 19

VIII.

Question 20

What are the features of von Willebrand disease?

Inheritance?

Answer 20

Variable reduction in FVIII levels.
Mucotaneous, post operative and post-partum bleeding.
Autosomal dominant.

Question 21

How is vWD treated? (5)

Answer 21

Antifibrinolytics: tranexamic acid.
DDAVP.
vWF concentrates.
Hepatitis vaccination.
COCP for menorrhagia.

Question 22

How does DDAVP work? (vWD Rx).

Answer 22

Increases release of vWF from stores.

Temporary effect that decreased on repeat dosing.

Question 23

Which hereditary coagulation factor deficiency is common in the Ashkenazi Jew population?

Answer 23

FXI.

Question 24

Which coagulation factor deficiency does not constitute a bleeding disorder?

Answer 24

FXII.

Question 25

Which coagulation factor deficiencies lead to a prolonged APTT?

Answer 25

XII.
XI.
IX.
VIII (vWD and haemophilia).

Question 26

Which coagulation factor deficiency leads to a prolonged PT?

Answer 26

VII.

Question 27

Which coagulation factor deficiencies lead to a prolonged APTT and PT? (5)

Answer 27

X.
V.
II.
I.
XIII.

Question 28

What are deficiencies seen in Haemophilia?

Answer 28

A: VIII.
B: IX.

Question 29

How is haemophilia inherited?

Answer 29

X linked recessive.
Expressed in males, carried in females.
Doesn’t get worse through generations.

Question 30

What are the degrees of severity in haemophilia?

Answer 30

Mild: 6-50%.
Moderate: 1-5%.
Severe: less than 1%

Question 31

How is haemophilia treated? (5)

Answer 31

Missing protein replacement. 
DDAVP.
Recombinant factor concentrates.
Antifibrinolytics.
Vaccination against Hep A + B.

Question 32

What is the major complication of haemophilia treatment?

Treated?

Answer 32

Inhibitor development.
Occurs in A > B.
Results in poor response to treatment.
Rx: eradication of inhibitor through very high dosage.

Question 33

Name 6 causes of bleeding with normal coagulation screens.

Answer 33

Thrombocytopenia.
Platelet abnormalities.
vWD.
Factor XIII deficiency.
Vascular disorder.
Disorder of fibrinolysis.