Heritable bleeding disorders

Question 1

Haemostasis

Answer 1

• Haemostasis exists in a balance between bleeding and clotting

Question 2

Breech of vasointegrity =

Answer 2

• Initial vasoconstriction, then activation of platelets at the site of vascular injury = adhere to the area of damaged vessel become activated and aggregate to form a plug
• Coagulation is then activated, and a fibrin plug is formed

Question 3

glycoprotein 1b9

Answer 3

• receptor for vWF

Question 4

Extrinsic pathway of coagulation cascade

Answer 4

• Activated first
• Exposure of tissue factor, binds + activates factor V11
• Factor V11a activates factor X
• Xa + Va cleaves prothrombin to produce thrombin
• formation of fibrin from fibrinogen

Question 5

Intrinsic pathway of coagulation cascade

Answer 5

• Involved when blood gets into contact with a foreign surface
• When thrombin is generated it feedbacks and directly activates factor XI

Question 6

Common pathway

Answer 6

Where the intrinsic and extrinsic pathways of the coagulation cascade interact.
- can’t get fibrin without activation of Factor X

Question 7

Fibrinolysis

Answer 7

• Plasma proteins circulate and become active when required
• plasmin breaks down cross-linked fibrin into fibrin degradation products
• Plasmin is generated by the action of tissue plasminogen activator on inert plasminogen

Question 8

Bleeding disorder types

Answer 8

• Congenital – usually single gene defect
• Acquired – often multiple defects
• Platelet/vessel wall defect - mucosal and skin bleeding - easy bruising, petechial rash, heavy periods, nose/gum bleeds.
• Coagulation defect – deep muscular bleeds, following trauma

Question 9

What to ask when taking a history of a patient with bleeding

Answer 9

• Ask about previous bleeding
• Response to challenges
• Severity of bleeding
• Systemic illness

Question 10

Appropriate investigations for patients with bleeding

Answer 10

• Firstly - FBC and blood film
• Coagulation screen and Clauss fibrinogen
• Prothrombin time (PT) = measuring extrinsic pathway, APTT = measuring intrinsic pathway
• vWF profile
• If all normal and suspicion remains – FXIII assay and assay of alpha2anti-plasmin

Question 11

A coagulation screen includes the following tests

Answer 11

• Prothrombin Time (PT)
• Activated Partial Thromboplastin Time (APTT)
• Fibrinogen

Question 12

Normal coagulation screen results

Answer 12

• Prothrombin Time (PT) = 10–14 seconds
• Activated Partial Thromboplastin Time (APTT) = 22–36 seconds
• Clauss Fibrinogen = 1.5–4.5 g/l

Question 13

Platelet/vessel wall defects

Answer 13

• All give rise to prolonged bleeding time
• Abnormal vessel walls due to scurvy
• vWD - abnormal interaction between platelets and cell walls

Question 14

Children with meningococcal meningitis get what?

Answer 14

• Will get petechial rash, often because their blood platelet count drops and/or platelets are not working normally

Question 15

Von Willebrand Disease - 3 types

Answer 15

Type 1 = reduced production of normal molecule = deficiency of protein = milder bleeding disorder – MOST COMMON BLEEDING DISORDER, F=M

• Type 2 = normal amount of abnormal molecule = still a mild disease but more manifestations than type 1
• Type 3 = absence of molecule = severe

Question 16

Von Willebrand factor (vWF)

Answer 16

• VWF synthesised and stores in endothelial cells
• acts as a glue for platelet aggregation to vessel walls
• acts as a carrier protein for FVIII and prolongs the life of it in the circulation

Question 17

Presentation of vWD

Answer 17

• Associated with defective primary haemostasis; skin and mucosal bleeding
• Mucocutaneous bleeding including menorrhagia (heavy periods)
• Postoperative and post-partum bleeding

Question 18

Treatment of vWD

Answer 18

• Antifibrinolytics - tranexamic acid
• DDAVP (desmopressin) - promotes release of vWF from storage granules
• Factor concentrates containing vWD (plasma derived)

Question 19

Haemophilia

Answer 19

• X linked recessive; expressed in males and carried by females – most common clotting factor deficiencies
• A = Factor VIII deficiency – 1/5000
• B = Factor IX deficiency; less common
• Severity level is consistent between family members

Question 20

Factor levels in haemophilia

Answer 20

• Normal Factor VIII/IX = 50—100%;
• Mild = 6-50%;
• Moderate = 1-5%;
• Severe = <1%

Question 21

Types of bleed in haemophilia

Answer 21

• Spontaneous/post traumatic
• Joint bleeding = haemarthrosis
• Muscle haemorrhage in neck - threat to airways
• Leads to MSK disability

Question 22

Treatment of Haemophilia

Answer 22

• Severe = replacement of missing clotting protein
• Mild/moderate - DDAVP
• Factor concentrates
• Anti-fibrinolytic agents

Question 23

Why does DDAVP not work for Haemophilia B

Answer 23

• factor IX not carried in circulation by vWF

Question 24

Complications of treatment

Answer 24

• TTI = transfusion transmitted infections

- Inhibitor development, HA>HB - factor being infused does not work

Question 25

How is the inhibitor eradicated

Answer 25

- Immune tolerance induction = child is exposed to factor VIII over a long time