Bleeding disorders

Question 1

Definition of von Willebrand disease (VWD)?

Answer 1

most common inherited cause of abnormal bleeding. It is usually due to a reduced quantity or reduced quality of von Willebrand factor.

Question 2

Risk factors for VWD

Answer 2

Family history

Question 3

The underlying genetic causes of VWF is what?

Answer 3

Autosomal dominant
The causes involve a deficiency, absence or malfunctioning of von Willebrand factor (VWF).

Question 4

Type 1 VWF pathophysiology

Answer 4

most common, autosomal dominant condition and can lead to reduced or defective production of vWF

Question 5

Type 2 VWF pathophysiology

Answer 5

quantity of vWF is fine but quality is affected. 4 subtypes

• A: vWF can attach to collagen and factor VIII, but unable to bind platelets
• B: vWF binds to platelets in the bloodstream, without injury. These platelets are cleared by the liver and spleen causing thrombocytopenia
• M: vWF can attach to collagen and factor VIII, but unable to bind platelets
• N: vWF binds to collagen and platelets, but not to factor VIII

Question 6

Type 3 VWF pathophysiology

Answer 6

rarest and most severe, autosomal recessive, individuals may have no vWF factor!

Question 7

S + S of VWF

Answer 7

• Easy, prolonged or heavy bleeding e.g.
  
  • Bleeding gums with brushing
  • Nose bleeds (epistaxis)
  • Heavy menstrual bleeding (menorrhagia)
  • Heavy bleeding during surgical operations
    Easy bruising
    Severe cases:
    Joint bleeding
    Muscle bleeding
    GI bleeding

Question 8

Investigation and diagnosis of VWF

Answer 8

based on a history of abnormal bleeding, family history, bleeding assessment tools and laboratory investigations.

• Platelets count: usually normal except in type IIB
• Prothrombin time: tests the extrinsic and common pathway and so is normal
• Activated partial thromboplastin time: tests the intrinsic and common pathways, usually prolonged
• Measurement of vWF antigen

Question 9

Management of VWF

Answer 9

• Desmopressin:can be used to stimulates the release of VWF
• VWFcan be infused
• Factor VIIIis often infused along with plasma-derived VWF
• Management of women with heavy periods

Question 10

What are haemophilia A and B

Answer 10

inherited severe bleeding disorders.

Question 11

Epidemiology of Haemophilia A and B

Answer 11

Almost exclusively affects males (X-linked recessive)

Question 12

Aetiology of Haemophilia A and B

Answer 12

• Inherited
• Acquired:
  
  • Liver failure
  • Vitamin K deficiency
  • Autoimmunity against a clotting factor
  • ## Disseminated intravascular coagulation

Question 13

What happens in haemophilia?

Answer 13

decrease in the amount or function of one or more of the clotting factors which makes secondary haemostasis less effective and allows more bleeding to happen.

Question 14

Haemophilia A is caused by what?

Answer 14

deficiency in factor VIII.
Mutated genes are called F8 - on X chromosome

Question 15

Haemophilia B is caused by what?

Answer 15

deficiency in factor IX.
Mutated genes called F9 - X chromosomes

Question 16

Acquired causes of haemophilia A and B

Answer 16

• Liver failure: as the liver is responsible for many of the clotting factors
• Vitamin K deficiency: as vitamin K is needed by many enzymes to synthesise a lot of the clotting factors
• Autoimmunity against a clotting factor
• Disseminated intravascular coagulation

Question 17

S + S of Haemophilia

Answer 17

Abnormal bleeding
Excessive Bleeding
- Ecchymosis: easy bruising
- Spontaneous haemorrhage
- Haematomas: collections of blood outside the blood vessels
- Haemoarthrosis: bleeding into joint

Question 18

What is diagnosis of haemophilia usually based on?

Answer 18

bleeding scores, coagulation factor assays and genetic testing.
- Platelets count: usually normal
- Prothrombin time: tests the extrinsic and common pathway and so is normal
- Activated partial thromboplastin time: tests the intrinsic and common pathways, usually prolonged

Question 19

Differential diagnosis of haemophilia

Answer 19

• Von Willebrand Disease: can present similarly to haemophilia
• Platelets dysfunction

Question 20

Treatment of haemophilia

Answer 20

• Avoid contact sports and medicines that promote bleeding e.g. aspirin
• IV infusion of deficient clotting factor (either prophylactic or in response to bleeding)
  
  • Complication: if patients initially had very low levels of the clotting factor, the immune system might mount an attack against the IV clotting factors, potentially leading to anaphylaxis
• Desmopressin: to stimulate the release of von Willebrand Factor
• Antifibrinolytics e.g. tranexamic acid

Question 21

complications of haemophilia

Answer 21

• Bleeds into the brain are a dangerous complication: can cause a stroke or increased intracranial pressure
• Haemarthrosis: can cause problems with joints

Question 22

What is Disseminated intravascular coagulation (DIC)

Answer 22

acquired syndrome characterised by activation of coagulation pathways, resulting in formation of intravascular thrombi and depletion of platelets and coagulation factors.

Out of control clotting - leads to thrombus and reduction of platelets

Question 23

What does DIC describe

Answer 23

a situation in which the process of haemostasis starts to run out of control.

Question 24

Pathophysiology of DIC

Answer 24

Pathology (sepsis, trauma, malignanacy) causes release of procoagulant (eg Tissue Factor) tipping scales for clot formation
Causes blood clots to form leading to ischemia , necrosis and eventually organ damage

Question 25

What is consumption coagulopathy in DIC

Answer 25

Excess clotting consumes platelets and clotting factors.

Without enough platelets circulating in the blood, other parts of the body begin to bleed with even the slightest damage to the blood vessel walls.

Question 26

Clinical manifestations of DIC

Answer 26

• Patient is often acutely ill and shocked
• Bleeding may occur from the mouth, nose and venepuncture sites and there
  may be widespread ecchymoses
• Confusion
• Bruising
• Thrombotic events occur as a result of vessel occlusion by fibrin and platelets - any organ may be involved but the skin, brain and kidneys are most affected

Question 27

Investigations of DIC

Answer 27

• Platelet count: low
• Fibrinogen: low
• D-dimer: breakdown product of fibrin, raised
• Prothrombin time: prolonged
• Partial thromboplastin time: prolonged
  History