Haemostasis III: vWD and Haemophilia

Question 1

What is Haemophilia A?

Answer 1

Haemophilia A is an X-linked bleeding disorder caused by defective synthesis or synthesis of dysfunctional factor VIII molecules or a combination of both.

Question 2

What causes Haemophilia A?

Answer 2

Haemophilia A is caused by mutations in the F8 gene.

Question 3

Where is the F8 gene located?

Answer 3

The F8 gene is located on Xq28.

Question 4

What is the pathophysiology of Haemophilia A?

Answer 4

The pathophysiology of Haemophilia A is based on insufficient generation of thrombin by the IXa/VIIIa complex of the intrinsic pathway.

Question 5

What are the genetic inheritance patterns of Haemophilia A?

Answer 5

Haemophilia A follows an X-linked recessive inheritance pattern.

Question 6

What is the probability of sons being affected if the mother is a carrier of Haemophilia A?

Answer 6

The probability of sons being affected if the mother is a carrier is 50%.

Question 7

What is the probability of daughters being carriers if the mother is a carrier and the father is normal?

Answer 7

The probability of daughters being carriers if the mother is a carrier and the father is normal is 50%.

Question 8

What are the types of genetic alterations that can lead to Haemophilia A?

Answer 8

Genetic alterations leading to Haemophilia A can include gene rearrangements, missense mutations, nonsense mutations, abnormal splicing, deletions, and insertions of genetic elements.

Question 9

What are the methods for carrier detection in Haemophilia A?

Answer 9

Methods for carrier detection in Haemophilia A include family history, measuring factor VIII levels, vWF ratio, Southern blot technique, and prenatal DNA analysis.

Question 10

How is Haemophilia A clinically classified?

Answer 10

Haemophilia A is clinically classified into mild, moderate, and severe based on factor VIII levels.

Question 11

What are the characteristics of mild Haemophilia A?

Answer 11

Mild Haemophilia A is characterized by factor levels of 6-30% of normal, with rare spontaneous bleeds and bleeding secondary to trauma or surgery.

Question 12

What are the characteristics of moderate Haemophilia A?

Answer 12

Moderate Haemophilia A is characterized by factor levels of 1-5% of normal, with occasional spontaneous bleeds and bleeding secondary to trauma or surgery.

Question 13

What are the characteristics of severe Haemophilia A?

Answer 13

Severe Haemophilia A is characterized by factor levels ≤ 1% of normal, with spontaneous bleeds from early infancy requiring factor replacement.

Question 14

What is haemarthrosis and how common is it in Haemophilia A?

Answer 14

Haemarthrosis is bleeding into the joints and accounts for approximately 75% of bleeding episodes in Haemophilia A.

Question 15

Which joints are most frequently affected by haemarthrosis?

Answer 15

Hinge joints such as knees, elbows, and ankles are more frequently affected by haemarthrosis.

Question 16

What are the symptoms and complications of haemarthrosis?

Answer 16

Symptoms of haemarthrosis include mild discomfort progressing to severe pain, joint swelling, warmth, limited motion, and mild fever. Complications include joint deformity, muscle atrophy, and chronic synovitis.

Question 17

What are haematomas and how are they related to clotting factor deficiencies?

Answer 17

Haematomas are characteristic of clotting factor deficiencies and may occur with or without trauma.

Question 18

What are the potential complications of haematomas in Haemophilia A?

Answer 18

Haematomas can stabilize and resorb or enlarge progressively, potentially compressing vital organs.

Question 19

What are the neurologic complications associated with Haemophilia A?

Answer 19

Neurologic complications associated with Haemophilia A include intracranial bleeds and spinal canal bleeding.

Question 20

What should be done immediately if an intracranial bleed is suspected in a patient with Haemophilia A?

Answer 20

Immediate factor replacement should be initiated if an intracranial bleed is suspected, even before imaging.

Question 21

What are the lab features of Haemophilia A?

Answer 21

Lab features of Haemophilia A include prolonged APTT, normal PT, BT, and TT, and definitive diagnosis with factor VIII assay.

Question 22

What are the treatment options for Haemophilia A?

Answer 22

Treatment options for Haemophilia A include avoiding NSAIDs, using acetaminophen and selective COX-2 inhibitors, and factor replacement therapy.

Question 23

What is the recommended approach to Factor VIII replacement therapy?

Answer 23

Factor VIII replacement therapy options include FFP, cryoprecipitate, lyophilized VIII, plasma-derived VIII, recombinant DNA-produced VIII, and porcine VIII.

Question 24

How is the required dose of Factor VIII calculated

Answer 24

The required dose of Factor VIII is calculated based on the patient’s plasma volume and desired factor level, typically 1 U per kg body weight raises the level by 0.02 U/ml.

Question 25

What is the half-life of Factor VIII?

Answer 25

The half-life of Factor VIII is 8-12 hours.

Question 26

What are the treatment options for patients with inhibitors of Factor VIII?

Answer 26

Treatment options for patients with inhibitors of Factor VIII include immune tolerance induction, porcine FVIII, FVIII inhibitor-bypassing agents, plasmapheresis, IVIG, and immunosuppressive therapy.

Question 27

What is von Willebrand Disease (vWD)?

Answer 27

von Willebrand Disease (vWD) is the commonest inherited bleeding disorder, affecting approximately 1 in 100 people.

Question 28

What are the types of vWD?

Answer 28

The types of vWD are Type 1, Type 2, and Type 3.

Question 29

What is the inheritance pattern of vWD?

Answer 29

vWD follows an autosomal recessive inheritance pattern.

Question 30

What is the role of von Willebrand factor (vWF) in haemostasis?

Answer 30

von Willebrand factor (vWF) plays a central role in haemostasis as a carrier protein for factor VIII and provides an adhesive interface between platelets and the injured vessel wall.

Question 31

Where is vWF produced?

Answer 31

vWF is produced exclusively in endothelial cells and megakaryocytes.

Question 32

What are the treatment options for vWD?

Answer 32

Treatment options for vWD include replacement therapy and DDAVP.