Heritable bleeding disorders Flashcards
What is the primary haemostatic pathway?
Aggregation of platelets.
What is the secondary haemostatic pathway?
Coagulation and formation of fibrin clot
What are alpha granules?
Found within platelets. Contain adhesive proteins, coagulation factors, fibrinolytic factors, growth factors, regulators of angiogenesis etc
What are the primary agonists of platelets?
- ADP
- thrombin
- TXA2
- epinephrine
- serotonin
- PAF
What is the mechanism of action of aspirin?
Inhibits the action of COX enxymes, which inhibits the production of thromboxane (facilitates platelet aggregation) and other pro-inflammatory molecules.
Which part of the clotting pathway is tested by the activated partial thromboplastin time test?
Intrinsic - (12)XIIa, (11)XIa, (9)IXa & (8)VIII
Which part of the clotting pathway is tested by the prothrombin time test?
Extrinsic (7)VIIa & TF
Give examples of procoagulant factors?
- Platelets
- Clotting factors
Give examples of anti-coagulant factors?
- Protein C
- Protein S
- Anti-thrombin III
- Fribrinolytic system
What is the main difference between congenital and acquired bleeding disorders?
- CONGENITAL - Usually single defect
- ACQUIRED - Often multiple defects
What is the focus of the signs and symptoms in platelet/vessel wall defects?
Mucosal and skin
What is the focus of signs and symptoms in coagulation defects?
Deep muscular and joint bleeds. Bleeding following trauma.
What sign does all platelet/vessel wall defects give rise to?
Prolonged bleeding time
Why do platelet/vessel wall defects give rise to prolonged bleeding times?
- Reduced number of platelets
- Abnormal platelet function
- Abnormal vessel wall
- Abnormal interaction between platelets and vessel wall e.g. Von Willebrand disease
What signs/symptoms are present in vascular/platelet defects?
- Spontaneous petechiae and superficial bruises
- Bleeding immediate; prolonged and non-recurrent
What signs/symptoms are present in coagulation defects?
- Deep, spreading haematoma
- Haemarthrosis
- Retroperitoneal bleeding
- Bleeding prolonged and often recurrent
What is Von Willibrand Disease?
A qualitative or quantitative deficiency of von Willebrand factor (vWF), a multimeric protein that is required for platelet adhesion.
What is the function of von Willibrand Factor?
Binds to various glycoproteins, mainly factor (8)VIII and is important in platelet adhesion.
What are the features of von Willibrand Disease?
- Most common heritable bleeding disorder
- Mainly autosomal dominant inheritance
- Associated with defective primary haemostasis
- Variable reduction in Factor (8)VIII levels
- Mucocutaneous bleeding including menorrhagia
- Postoperative and post partum bleeding
- Variable penetrance for mild types
- Diagnosis of mild vWD difficult due to confounding factors
- Blood group O: lower levels of vWF
What are the treatment options for von Willibrand Disease?
- Antifibrinolytics: tranexamic acid
- DDAVP (type 1 vWD)
- Factor concentrates containing vWD (plasma derived)
- Vaccination against hepatitis
- COCP for menorrhagia
What is the mode of inheritance for factor (12)XII deficiency and how common is it?
Autosomal recessive - rare
What is the mode of inheritance for factor (9)IX haemophilia B and how common is it?
Sex-linked recessive - uncommon
What is the mode of inheritance for factor (8)VIII haemophilia A and how common is it?
Sex-linked recessive - uncommon
What is the mode of inheritance for von Willibrand Disease?
Autosomal dominant - common
