Heritable bleeding disorders Flashcards Preview

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Flashcards in Heritable bleeding disorders Deck (35):
1

What is the primary haemostatic pathway?

Aggregation of platelets.

2

What is the secondary haemostatic pathway?

Coagulation and formation of fibrin clot

3

What are alpha granules?

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

4

What are the primary agonists of platelets?

- ADP
- thrombin
- TXA2
- epinephrine
- serotonin
- PAF

5

What is the mechanism of action of aspirin?

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

6

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

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

7

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

Extrinsic (7)VIIa & TF

8

Give examples of procoagulant factors?

- Platelets
- Clotting factors

9

Give examples of anti-coagulant factors?

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

10

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

- CONGENITAL - Usually single defect
- ACQUIRED - Often multiple defects

11

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

Mucosal and skin

12

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

Deep muscular and joint bleeds. Bleeding following trauma.

13

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

Prolonged bleeding time

14

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

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

15

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

- Spontaneous petechiae and superficial bruises
- Bleeding immediate; prolonged and non-recurrent

16

What signs/symptoms are present in coagulation defects?

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

17

What is Von Willibrand Disease?

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

18

What is the function of von Willibrand Factor?

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

19

What are the features of von Willibrand Disease?

- 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

20

What are the treatment options for von Willibrand Disease?

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

21

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

Autosomal recessive - rare

22

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

Sex-linked recessive - uncommon

23

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

Sex-linked recessive - uncommon

24

What is the mode of inheritance for von Willibrand Disease?

Autosomal dominant - common

25

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

Autosomal recessive - very rare

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?

Autosomal recessive - very rare

27

What percentage of cases of haemophilia are new mutations?

30%

28

What are the degrees of severity of haemophilia?

- 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 = ?

29

What types of bleed my occur in haemophilia?

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

30

What are the treatment options for haemophilia?

- 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

31

What is inhibitor development?

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

32

How frequent is inhibitor development?

25% of haemophilia A
More common in A than B

33

What are the consequences of inhibitor development?

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

34

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

- FBC andd blood film
- Coagulation and Clauss fibrinogen

35

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

D-dimer

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