Inherited Bleeding Disorders

Question 1

What are inherited bleeding disorders?

Answer 1

Disorders due to the absence or deficiency of specific clotting proteins acting as procoagulants in the clotting cascade.

Question 2

What are the major inherited bleeding disorders?

Answer 2

• Hemophilia A
• Hemophilia B
• Von Willebrand Diseases (VWD)

Question 3

What does the term ‘hemophilia’ derive from?

Answer 3

‘Haima’ meaning blood and ‘philia’ meaning affection.

Question 4

What is the most common inherited bleeding disorder?

Answer 4

Von Willebrand Disease (VWD).

Question 5

How is Hemophilia A characterized?

Answer 5

Deficiency in factor VIII, leading to prolonged bleeding, particularly into joints and muscles.

Question 6

What is the prevalence of Hemophilia A?

Answer 6

Affects approximately 1 in 5,000 male births worldwide.

Question 7

What is the genetic inheritance pattern of Hemophilia?

Answer 7

Sex-linked recessive genetic disorder affecting the X chromosome.

Question 8

What is Hemophilia B characterized by?

Answer 8

Decrease in factor IX clotting activity.

Question 9

What is the prevalence of Hemophilia B?

Answer 9

Affects approximately 1 in 25,000 male births worldwide.

Question 10

What is Hemophilia C?

Answer 10

A rare autosomal genetic disorder involving a lack of functional clotting factor XI.

Question 11

How does Hemophilia A lead to excessive bleeding?

Answer 11

Clot formation is delayed due to markedly decreased thrombin generation.

Question 12

What are common clinical presentations of Hemophilia?

Answer 12

• Prolonged bleeding post-circumcision
• Hemarthrosis
• Hematuria
• Dental and surgical bleeding

Question 13

What laboratory test results are expected in Hemophilia A?

Answer 13

• Complete Blood Count (CBC): Normal
• Clotting Time: Prolonged
• Activated Partial Thromboplastin Time (aPTT): Prolonged

Question 14

What is the main goal of management for Hemophilia?

Answer 14

Prevention of bleeding.

Question 15

What is Factor Replacement Therapy?

Answer 15

Administration of recombinant or plasma-derived Factor VIII to restore clotting activity.

Question 16

What is the function of von Willebrand factor (vWF)?

Answer 16

• Mediates adhesion of platelets to subendothelium
• Stabilizes clotting factor VIII in circulation

Question 17

What are the types of Von Willebrand Disease (VWD)?

Answer 17

• Type 1 (Mild)
• Type 2 (Qualitative)
• Type 3 (Severe)

Question 18

What characterizes Type 1 VWD?

Answer 18

Partial deficiency of vWF, leading to mild bleeding symptoms.

Question 19

What characterizes Type 2A VWD?

Answer 19

Normal amounts of vWF but defective in binding to platelets, leading to impaired platelet aggregation.

Question 20

What is the inheritance pattern of Type 2B VWD?

Answer 20

Autosomal dominant inherited disorder.

Question 21

What are common symptoms of Von Willebrand Disease?

Answer 21

• Easy bruising
• Nosebleeds
• Prolonged bleeding after dental procedures

Question 22

What is the incidence of Von Willebrand Disease?

Answer 22

1 in 100, but symptomatic in 1 in 10,000.

Question 23

What is a key feature of Hemophilia C?

Answer 23

Bleeding risk is not always influenced by the severity of the deficiency.

Question 24

What is the primary defect in Type 2B Von Willebrand Disease (VWD)?

Answer 24

A mutation in large multimers of VWF resulting in increased affinity for platelets

This leads to abnormal platelet aggregation and premature removal of platelet-VWF complexes from circulation.

Question 25

What are common bleeding symptoms associated with VWD?

Answer 25

* Mucosal bleeding (nosebleeds, gum bleeding) * Easy bruising * Heavy menstrual bleeding * Spontaneous bleeding in severe cases

Question 26

How is Type 2M VWD inherited?

Answer 26

It can be either Autosomal dominant or Autosomal recessive ## Footnote This type features normal size multimers but a defect in binding to platelets.

Question 27

What characterizes Type 3 VWD?

Answer 27

Complete absence of VWF in circulation ## Footnote It is the most severe form, leading to severe factor VIII deficiency.

Question 28

Fill in the blank: Type 2N VWD leads to a secondary ______ deficiency.

Answer 28

factor VIII

Question 29

What is a common clinical feature of all types of VWD?

Answer 29

Easy bruising ## Footnote Other features may include prolonged bleeding after minor injuries and recurrent nosebleeds.

Question 30

What is the inheritance pattern of Type 2B VWD?

Answer 30

Autosomal dominant

Question 31

What laboratory tests are used for diagnosing Von Willebrand disease?

Answer 31

* Full Blood Count * Blood Film Examination * APTT * Platelet Function Assay (PFA-test) * Plasma VWF antigen level (VWF:Ag) * Plasma VWF activity (VWF:Rco and VWF:CB) * Factor VIII Assay/Activity * VWF Multimer Gel Electrophoresis * Bleeding time

Question 32

True or False: Type 3 VWD can present with spontaneous internal bleeding.

Answer 32

True

Question 33

What treatment is effective for Type 1 and some cases of Type 2 VWD?

Answer 33

Desmopressin (DDAVP) ## Footnote It stimulates the release of vWF and factor VIII from endothelial cells.

Question 34

What is the role of antifibrinolytics in managing VWD?

Answer 34

They help stabilize clots and are useful for mucosal bleeding ## Footnote Examples include tranexamic acid and epsilon-aminocaproic acid.

Question 35

Fill in the blank: In Type 2N VWD, the defect leads to a decreased half-life of ______.

Answer 35

factor VIII

Question 36

What general measure should patients with VWD avoid?

Answer 36

Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) ## Footnote These can impair platelet function.

Question 37

What are the symptoms of Type 2B VWD?

Answer 37

* Mild to moderate bleeding * Spontaneous bleeding from mucosal surfaces

Question 38

What is the primary cause of bleeding in Type 3 VWD?

Answer 38

Severe impairment of platelet adhesion due to the absence of VWF ## Footnote This leads to disruption of coagulation and severe bleeding tendencies.