11. Other blood disorders Flashcards
What is hemostasis?
Mechanism that leads to cessation of bleeding from a blood vessel
What is the role of VWF?
Central role in haemostasis - adheres platelets to subendothelial tissue, stabilises coagulation factor VIII in circulation & protects it from degradation
How is type 1 VWD characterised?
How is it inherited?
30% of VWD
Partial quantitative deficiency
Mild mucocutaneous bleeding
AD but incomplete penetrance and variable expressivity
How is type 2 VWD characterised?
How is it inherited?
60% VWD
Qualitative deficiency, high penetrance
- 2A - AD
- 2B - GoF, AD
- 2M - AD
- 2N - AR
All mild-to-moderate bleeding except 2N (excessive with surgery)
How is type 3 VWD characterised?
How is it inherited?
Complete quantitative deficiency
Severe mucocutaneous and musculoskeletal bleeding
AR
What is the genotype-phenotype correlation in VWD?
Type 1 - mostly missense
Type 2 - majority located in A1 domain
Type 3 - mostly LoF
How is von Willebrand disease treated?
Desmopressin - stimulates production of clotting FVIII
F8 + VW clotting factor concentrates - given intravenously
How is haemophilia characterised?
Reduced clotting activity due to defective platelets or plasma protein involved in clotting
What causes haemophilia?
Deficiency of coagulation F8 (haem A) or F9 (haem B) - both XLR
How does haemophilia present?
Spontaneous bleeding in joints, muscles, inner organs, haemorrhage into CNS
Bleeding after injury, surgery etc
What’s the most common cause of haemophilia A?
How does it arise?
F8 intron 22 inversion - 50% of severely affected patients
Caused by intra-chromosomal recombination during meiosis (NAHR within the same chromosome)
Usually in spermatogensis due to lack of second X chr for homologous alignment
Exons 1-22 inverted and relocated –> no F8 protein
Why do pregnant haem B carriers have higher risk of bleeding during delivery than haem A carriers?
Female carriers may show mild disease due to skewed X in activation
F8 levels rise in pregnancy, F9 levels do not
How are inherited thrombophilias characterised?
Increased risk of venous thrombosis due to inappropriate formation of clots
What are the 2 most common types of inherited thrombophilia?
Factor V Leiden
Factor II prothrombin thrombophilia
What is the role of F5?
Coagulation factor activated when blood vessels are damaged
Binds to FXa
Complex converts prothrombin to thrombin - forms clot
