0402 - Bleeding Disorders

Question 1

What is von Willebrand factor?

Answer 1

Carrier molecule for factor VIII. Also binds to collagen following epithelial damage, allowing platelets to adhere.

Question 2

Briefly outline von Willebrand’s disease

Answer 2

A common, generally autosomal dominant (type I and II) disorder characterised by mucocutaneous bleeding of varying severity.

Question 3

What are the 3 types of vW disease?

Answer 3

Type I - Deficiency of qualitatively normal vWF - autosomal dominant.

Type II - Production of abnormal vWF (can’t bind either FVIII/platelets) - Autosomal dominant

Type III - Total deficiency of vWF - autosomal recessive, uncommon.

Question 4

What is the pathophysiology of von Willebrand disease?

Answer 4

Insufficient or damaged vWF prevents adequate clot formation (remembering that it binds to collagen, adheres platelets, and carries Factor VIII). Thus, person bleeds for longer than would otherwise be the case.

Question 5

How is vWD diagnosed?

Answer 5

Decreased levels of vWF and possibly FVIII

Defective platelet aggregation despite normal platelet levels.

Question 6

What is the pathophysiology of Haemophilias A and B?

Answer 6

Haemophilia A = deficiency in FVIII

Haemophilia B = deficiency in FIX

Question 7

What is the categorisation of haemophilia A? How does each present?

Answer 7

Mild 5-10% of normal Factor VIII levels - Spontaneous bleeding uncommon, but post-traumatic/surgical bleeds occur.

Moderate 1-5% of normal levels - Occasional spontaneous joint bleeds - post-traumatic/surgical bleeds occur.

Severe -

Question 8

What is chronic haemophilic arthropathy?

Answer 8

Repeated haemarthrosis over many years inflames the synovium and leads to angiogenesis, leading to more bleeding.

Eventually leads to ankylose joint, with muscle atrophy, and crippling deformities.

Question 9

How can Haemophilia B be differentiated from Haemophilia A?

Answer 9

Much less common. Can only be differentiated by relative factor VIII (A) or IX (B) levels.

Question 10

What are the tests you should do on ANY patient who appears to have a blood/bleeding-related disorder?

Answer 10

Full History and clinical assessment

Lab tests - FBC, Coag Factors, Clotting Times

Question 11

What is the genetics and incidence of Haemophilias A and B?

Answer 11

Both X-linked recessive. ⅓ spontaneous mutation.

Haemophilia A = 1/5000 male births
Haemophilia B = Uncommon