Inherited Bleeding Disorders Flashcards
What are inherited bleeding disorders?
Disorders due to the absence or deficiency of specific clotting proteins acting as procoagulants in the clotting cascade.
What are the major inherited bleeding disorders?
- Hemophilia A
- Hemophilia B
- Von Willebrand Diseases (VWD)
What does the term ‘hemophilia’ derive from?
‘Haima’ meaning blood and ‘philia’ meaning affection.
What is the most common inherited bleeding disorder?
Von Willebrand Disease (VWD).
How is Hemophilia A characterized?
Deficiency in factor VIII, leading to prolonged bleeding, particularly into joints and muscles.
What is the prevalence of Hemophilia A?
Affects approximately 1 in 5,000 male births worldwide.
What is the genetic inheritance pattern of Hemophilia?
Sex-linked recessive genetic disorder affecting the X chromosome.
What is Hemophilia B characterized by?
Decrease in factor IX clotting activity.
What is the prevalence of Hemophilia B?
Affects approximately 1 in 25,000 male births worldwide.
What is Hemophilia C?
A rare autosomal genetic disorder involving a lack of functional clotting factor XI.
How does Hemophilia A lead to excessive bleeding?
Clot formation is delayed due to markedly decreased thrombin generation.
What are common clinical presentations of Hemophilia?
- Prolonged bleeding post-circumcision
- Hemarthrosis
- Hematuria
- Dental and surgical bleeding
What laboratory test results are expected in Hemophilia A?
- Complete Blood Count (CBC): Normal
- Clotting Time: Prolonged
- Activated Partial Thromboplastin Time (aPTT): Prolonged
What is the main goal of management for Hemophilia?
Prevention of bleeding.
What is Factor Replacement Therapy?
Administration of recombinant or plasma-derived Factor VIII to restore clotting activity.
What is the function of von Willebrand factor (vWF)?
- Mediates adhesion of platelets to subendothelium
- Stabilizes clotting factor VIII in circulation
What are the types of Von Willebrand Disease (VWD)?
- Type 1 (Mild)
- Type 2 (Qualitative)
- Type 3 (Severe)
What characterizes Type 1 VWD?
Partial deficiency of vWF, leading to mild bleeding symptoms.
What characterizes Type 2A VWD?
Normal amounts of vWF but defective in binding to platelets, leading to impaired platelet aggregation.
What is the inheritance pattern of Type 2B VWD?
Autosomal dominant inherited disorder.
What are common symptoms of Von Willebrand Disease?
- Easy bruising
- Nosebleeds
- Prolonged bleeding after dental procedures
What is the incidence of Von Willebrand Disease?
1 in 100, but symptomatic in 1 in 10,000.
What is a key feature of Hemophilia C?
Bleeding risk is not always influenced by the severity of the deficiency.
What is the primary defect in Type 2B Von Willebrand Disease (VWD)?
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.
What are common bleeding symptoms associated with VWD?
- Mucosal bleeding (nosebleeds, gum bleeding)
- Easy bruising
- Heavy menstrual bleeding
- Spontaneous bleeding in severe cases
How is Type 2M VWD inherited?
It can be either Autosomal dominant or Autosomal recessive
This type features normal size multimers but a defect in binding to platelets.
What characterizes Type 3 VWD?
Complete absence of VWF in circulation
It is the most severe form, leading to severe factor VIII deficiency.
Fill in the blank: Type 2N VWD leads to a secondary ______ deficiency.
factor VIII
What is a common clinical feature of all types of VWD?
Easy bruising
Other features may include prolonged bleeding after minor injuries and recurrent nosebleeds.
What is the inheritance pattern of Type 2B VWD?
Autosomal dominant
What laboratory tests are used for diagnosing Von Willebrand disease?
- 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
True or False: Type 3 VWD can present with spontaneous internal bleeding.
True
What treatment is effective for Type 1 and some cases of Type 2 VWD?
Desmopressin (DDAVP)
It stimulates the release of vWF and factor VIII from endothelial cells.
What is the role of antifibrinolytics in managing VWD?
They help stabilize clots and are useful for mucosal bleeding
Examples include tranexamic acid and epsilon-aminocaproic acid.
Fill in the blank: In Type 2N VWD, the defect leads to a decreased half-life of ______.
factor VIII
What general measure should patients with VWD avoid?
Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs)
These can impair platelet function.
What are the symptoms of Type 2B VWD?
- Mild to moderate bleeding
- Spontaneous bleeding from mucosal surfaces
What is the primary cause of bleeding in Type 3 VWD?
Severe impairment of platelet adhesion due to the absence of VWF
This leads to disruption of coagulation and severe bleeding tendencies.
