PBL 3 - Von Willebrand Disease Flashcards
List the three stages of response that normally occur to arrest bleeding after vascular injury and briefly outline their role in haemostasis. (3 marks) `
a) Vascular response (1/2 mark) vasoconstriction leading to reduced blood flow (1/2 mark)
b) Platelet response (1/2 mark) the platelets adhere to the edge of the damaged vessel and then
aggregate to form a platelet plug (1/2 mark)
c) The coagulation pathway (cascade) (1/2 mark)
tissue factor expressed on damaged cells initiates the cascade by binding to activated factor VII (1/2
mark)
Explain briefly the activation and role of tissue factor (factor III) in the coagulation pathway (3 marks)
Tissue factor (TF) is a protein found inside endothelium (in the subendothelial tissue) (1/2 mark).
Damage to endothelial cells exposes tissue factor to the circulating blood (1/2 mark). Factor VII is
converted by the exposed tissue factor to VIIa (1/2 mark) and the complex of TF with factor VIIa
catalyzes the conversion of factor X (the common pathway) to Xa (1/2 mark). Xa combines with
activated factor V (1/2 mark) converts prothrombin to thrombin, which in turn converts fibrinogen
to fibrin (1/2 mark).
Outline the steps involved in the removal of blood clots from blood vessels after the damage has been repaired (2 marks)
Tissue plasminogen activator (t-PA) (1/2 mark) is released from the repaired endothelium (1/2
mark). t-PA converts the inactive precursor protein plasminogen (1/2 mark) into plasmin. Plasmin is
a protease enzyme (1/2 mark ) that dissolves clots by breaking down fibrin (1/2 mark). (any four
half marks)
What parts of the coagulation pathway does the activated partial thromboplastin time (APTT)
measure (1 mark)?
APTT measures the efficiency of the intrinsic (1/2 mark) and common pathways (1/2 mark)
How does haemophilia B differ from haemophilia A? (1 mark)
Deficiency in different clotting factors Haemophilia B - deficiency of Factor IX (1/2 mark)
Haemophilia A - deficiency of Factor VIII (1/2 mark)
What is the normal bleeding time? (1)
2-9 mins
it tests platelet plug formation
How does the data in the table point towards von willebrand disease (2)
Normal factor 9 (not Hb B)
Haemophilia A as reduction in factor 8 however it is X-linked recessive so unlikely as mother has it (in males)
Factor 8 reduced
Long bleeding time - problem in aggregation and plug formation ( VWF assists in platelet adherence)
What is the function of VWF? (2)
Prevents the breakdown of factor 8 by binding factor VIII, a key clotting protein, and platelets in blood vessel walls, which help form a platelet plug during the clotting process.
What is the inheritance of von willebrand disease (2)
Chromosome 12
Type 1 + 2 - autosomal dominant
Type 3 - Autosomal recessive
Acquired - autoimmune
What are the different types of Vwd, what are the differences between them? (4)
Type 1 - Mild deficiency (60-80%) - mild bruising, menorrhagia, epistaxis (nosebleed)
Type 2 - Abnormal VWF (20-30%) - mild to moderate depending on subtype (2A,2B, 2M, 2N)
Type 3 - Severe deficiency of VWF - severe haemarthroses, spontaneous bleeding
Why should sharon be careful about her alcohol intake? (2)
- Liver cirrhosis – interferes with liver’s ability to produce coagulation factors
- VWD – avoid damaging liver as more vulnerable,
What is the action of desmopressin and tranexamic acid? (2)
Desmopressin - synthetic version of vasopressin, stimulates endothelial cells to release Vwf – also increases factor 8
Tranexamic acid- preventing blood clots from breaking down too quickly
What drugs should patients with VWD avoid? (1)
Aspirin as blocks thromboxane
use paracetamol
Side effect of desmopressin
Hyponatraemia
Management of VW disease
Desmopressin
Tranexamic acid
Factor 8 IV infusion or VWF concentrate
Oral contraceptives if heavy periods
