Heritable bleeding disorders

Question 1

What is the primary haemostatic pathway?

Answer 1

Aggregation of platelets.

Question 2

What is the secondary haemostatic pathway?

Answer 2

Coagulation and formation of fibrin clot

Question 3

What are alpha granules?

Answer 3

Found within platelets. Contain adhesive proteins, coagulation factors, fibrinolytic factors, growth factors, regulators of angiogenesis etc

Question 4

What are the primary agonists of platelets?

Answer 4

• ADP
• thrombin
• TXA2
• epinephrine
• serotonin
• PAF

Question 5

What is the mechanism of action of aspirin?

Answer 5

Inhibits the action of COX enxymes, which inhibits the production of thromboxane (facilitates platelet aggregation) and other pro-inflammatory molecules.

Question 6

Which part of the clotting pathway is tested by the activated partial thromboplastin time test?

Answer 6

Intrinsic - (12)XIIa, (11)XIa, (9)IXa & (8)VIII

Question 7

Which part of the clotting pathway is tested by the prothrombin time test?

Answer 7

Extrinsic (7)VIIa & TF

Question 8

Give examples of procoagulant factors?

Answer 8

• Platelets

- Clotting factors

Question 9

Give examples of anti-coagulant factors?

Answer 9

• Protein C
• Protein S
• Anti-thrombin III
• Fribrinolytic system

Question 10

What is the main difference between congenital and acquired bleeding disorders?

Answer 10

• CONGENITAL - Usually single defect

- ACQUIRED - Often multiple defects

Question 11

What is the focus of the signs and symptoms in platelet/vessel wall defects?

Answer 11

Mucosal and skin

Question 12

What is the focus of signs and symptoms in coagulation defects?

Answer 12

Deep muscular and joint bleeds. Bleeding following trauma.

Question 13

What sign does all platelet/vessel wall defects give rise to?

Answer 13

Prolonged bleeding time

Question 14

Why do platelet/vessel wall defects give rise to prolonged bleeding times?

Answer 14

• Reduced number of platelets
• Abnormal platelet function
• Abnormal vessel wall
• Abnormal interaction between platelets and vessel wall e.g. Von Willebrand disease

Question 15

What signs/symptoms are present in vascular/platelet defects?

Answer 15

• Spontaneous petechiae and superficial bruises

- Bleeding immediate; prolonged and non-recurrent

Question 16

What signs/symptoms are present in coagulation defects?

Answer 16

• Deep, spreading haematoma
• Haemarthrosis
• Retroperitoneal bleeding
• Bleeding prolonged and often recurrent

Question 17

What is Von Willibrand Disease?

Answer 17

A qualitative or quantitative deficiency of von Willebrand factor (vWF), a multimeric protein that is required for platelet adhesion.

Question 18

What is the function of von Willibrand Factor?

Answer 18

Binds to various glycoproteins, mainly factor (8)VIII and is important in platelet adhesion.

Question 19

What are the features of von Willibrand Disease?

Answer 19

• Most common heritable bleeding disorder
• Mainly autosomal dominant inheritance
• Associated with defective primary haemostasis
• Variable reduction in Factor (8)VIII levels
• Mucocutaneous bleeding including menorrhagia
• Postoperative and post partum bleeding
• Variable penetrance for mild types
• Diagnosis of mild vWD difficult due to confounding factors
• Blood group O: lower levels of vWF

Question 20

What are the treatment options for von Willibrand Disease?

Answer 20

• Antifibrinolytics: tranexamic acid
• DDAVP (type 1 vWD)
• Factor concentrates containing vWD (plasma derived)
• Vaccination against hepatitis
• COCP for menorrhagia

Question 21

What is the mode of inheritance for factor (12)XII deficiency and how common is it?

Answer 21

Autosomal recessive - rare

Question 22

What is the mode of inheritance for factor (9)IX haemophilia B and how common is it?

Answer 22

Sex-linked recessive - uncommon

Question 23

What is the mode of inheritance for factor (8)VIII haemophilia A and how common is it?

Answer 23

Sex-linked recessive - uncommon

Question 24

What is the mode of inheritance for von Willibrand Disease?

Answer 24

Autosomal dominant - common

Question 25

What is the mode of inheritance for factor (7)VII deficiency and how common is it?

Answer 25

Autosomal recessive - very rare

Question 26

What is the mode of inheritance of factor (10)X, (5)V, (2)II, (1)I & (13)XIII deficiency and how common is it?

Answer 26

Autosomal recessive - very rare

Question 27

What percentage of cases of haemophilia are new mutations?

Answer 27

30%

Question 28

What are the degrees of severity of haemophilia?

Answer 28

- Normal factor (8)VIII or (9)IX level = 50% - 150% - Mild Haemophilia - Factor (8)VIII or (9)IX level = 6% - 50% - Moderate Haemophilia - Factor (8)VIII or (9)IX level = 1% - 5% - Severe Haemophilia - Factor (8)VIII or (9)IX level = ?

Question 29

What types of bleed my occur in haemophilia?

Answer 29

- Spontaneous/Post traumatic - Joint Bleeding = Haemarthrosis - Muscle Haemorrhage - Soft Tissue - Life Threatening Bleeding

Question 30

What are the treatment options for haemophilia?

Answer 30

- Replacement of missing clotting protein:- On demand or Prophylaxis - DDAVP (Mild/Moderate Haemophilia A) - Factor Concentrates: Recombinant are products of choice - Antifibrinolytic Agents - Vaccination vs hepatitis A and B - Supportive Measures i.e. Icing, Immobilisation, Rest

Question 31

What is inhibitor development?

Answer 31

Development of an antibody to the exogenous factor being used to treat haemophilia.

Question 32

How frequent is inhibitor development?

Answer 32

25% of haemophilia A | More common in A than B

Question 33

What are the consequences of inhibitor development?

Answer 33

- Result in poor recovery and/or shortened half life of factor replacement therapy. - Poor clinical response to treatment - Specialist management of bleeds

Question 34

What tests should be performed in the case of a suspected bleeding disorder?

Answer 34

- FBC andd blood film | - Coagulation and Clauss fibrinogen

Question 35

What additional test would you perform in the case of a suspected acquired disorder?

Answer 35

D-dimer