Inherited 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 is the origin of the term ‘hemophilia’?
‘Hemophilia’ is derived from ‘haima’ meaning ‘blood’ and ‘philia’ meaning ‘affection’.
Which is the most common inherited bleeding disorder?
Von Willebrand Disease (VWD)
What is the prevalence of Hemophilia A?
Affects approximately 1 in 5,000 male births worldwide.
What is the inheritance pattern of Hemophilia?
Sex-linked recessive genetic disorder affecting the X chromosome.
What are the three known types of Hemophilia?
- Hemophilia A
- Hemophilia B
- Hemophilia C
What is the most common type of Hemophilia?
Hemophilia A
What causes prolonged bleeding in Hemophilia A?
Defective clot stabilization due to low levels of functional factor VIII.
What is the genetic cause of Hemophilia B?
Decrease in factor IX clotting activity.
How is Hemophilia C different from Hemophilia A and B?
It is an autosomal genetic disorder involving a lack of functional clotting factor XI.
What are common clinical presentations of Hemophilia?
- Prolonged bleeding post-circumcision
- Hemarthrosis
- Muscle hemorrhages
- Intracranial bleeding
Which laboratory test is prolonged in Hemophilia?
Activated Partial Thromboplastin Time (aPTT)
What is the goal of hemophilia management?
Prevention of bleeding.
What is Factor Replacement Therapy?
Administration of recombinant or plasma-derived factor to restore clotting activity.
What is Desmopressin used for in Hemophilia A?
To release stored Factor VIII from endothelial cells in mild cases.
What is the mainstay treatment for Hemophilia C?
Fresh Frozen Plasma (FFP)
What is the most common inherited bleeding disorder?
Von Willebrand Disease (VWD)
What are the functions of von Willebrand factor (vWF)?
- Mediates adhesion of platelets to subendothelium
- Stabilizes factor VIII
What are the three types of Von Willebrand Disease?
- Type 1 (Mild Form)
- Type 2 (Qualitative Form)
- Type 3 (Severe Form)
What characterizes Type 1 VWD?
Partial deficiency of vWF with normal function, leading to mild bleeding tendency.
What is the inheritance pattern of Type 2B VWD?
Autosomal dominant inherited disorder.
What is the prevalence of Type 1 VWD?
Accounts for about 70-80% of cases.
What is a key difference between Type 2A and Type 2B VWD?
Type 2A has defective binding to platelets, while Type 2B has increased affinity for platelets.
What are common symptoms of VWD?
- Easy bruising
- Nosebleeds
- Prolonged bleeding after dental procedures
What is the primary impact of von Willebrand factor (VWF) deficiency on platelets?
It impairs platelet adhesion and aggregation, resulting in bleeding.
List common bleeding symptoms associated with von Willebrand disease (VWD).
- Mucosal bleeding (nosebleeds, gum bleeding)
- Easy bruising
- Heavy menstrual bleeding
- Spontaneous bleeding in severe cases
What inheritance pattern is associated with Type 2B von Willebrand disease (VWD)?
Autosomal dominant
What mutation occurs in Type 2B VWD?
A mutation in the large multimers of VWF that results in an increased affinity for platelets.
What is the result of increased affinity for platelets in Type 2B VWD?
Abnormal platelet aggregation and premature removal of platelet-VWF complexes from circulation.
What is thrombocytopenia?
Low platelet count.
What are the inheritance patterns for Type 2M VWD?
- Autosomal dominant
- Autosomal recessive
Describe the defect in Type 2M VWD.
VWF has normal size multimers but a defect in its ability to bind to platelets effectively.
What is the main consequence of the defect in Type 2M VWD?
Impaired clot formation due to reduced platelet adhesion to the damaged vessel wall.
What is the primary issue in Type 2N VWD?
Reduced ability of VWF to bind and stabilize factor VIII.
What does Type 2N VWD mimic in its symptoms?
Hemophilia A.
What is the inheritance pattern of Type 3 VWD?
Autosomal recessive
What characterizes Type 3 VWD?
Complete absence of VWF in circulation.
What severe condition results from the absence of VWF in Type 3 VWD?
Severe factor VIII deficiency.
What are common clinical features of von Willebrand disease?
- Easy bruising
- Prolonged bleeding after minor injuries
- Recurrent nosebleeds (epistaxis)
- Heavy or prolonged menstrual bleeding
- Excessive bleeding during surgical procedures
- Spontaneous bleeding into joints and muscles in severe cases
What laboratory tests are used for the diagnosis of 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
What treatment is effective for Type 1 and some cases of Type 2 VWD?
Desmopressin (DDAVP)
What is vWF Replacement Therapy used for?
Administration of plasma-derived vWF concentrates for severe bleeding or surgical procedures, especially in Type 3 VWD.
What are antifibrinolytics, and when are they used?
Medications like tranexamic acid and epsilon-aminocaproic acid that help stabilize clots, useful for mucosal bleeding.
What hormonal therapy can be used for women with menorrhagia in VWD?
Combined oral contraceptives.
What general measure should be taken to avoid complications in VWD?
Avoidance of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs).
