Pathology - Haemostasis Flashcards
What is the definition of haemostasis?
The stoppage of bleeding or haemorrhage. May be via vasoconstriction, an obstruction, coagulation or surgical means.
What are the main functions of haemostasis?
- prevent bleeding
- prevent unnecessary coagulation, allow blood to flow
- make clot, control the clotting, break it down
Where are platelets produced?
In the bone marrow by megakaryocytes. They ‘bud’ from the cytoplasm
What is the normal life span of a platelet?
7-10 days
What is the normal platelet count?
150-400,000 per microlitre of blood
When does platelet adhesion occur?
When there is damage to the vessel wall and exposure of underlying tissues
What do platelets secrete?
ADP, thromboxane and other substances to become activated and activate other platelets. This helps initiate the clotting cascade.
Give some mediating factors of platelet clot formation
- Plt receptors - glycoproteins complexes
- Von willebrands factor
- fibrinogen
- collagen
- ADP
- thromboxane/arachidonic acid
- thrombin
What is the clotting cascade?
Amplification system activation of precursor proteins to generate thrombin. Thrombin converts soluble fibrinogen into insoluble fibrin, which meshes the initial platelet plug to make a stable clot.
Where are clotting factors made?
In the liver
Give some examples of natural anticoagulants
Proteins C and S, antithrombin, tissue factor pathway inhibitor
Give some examples of coagulation factors made in the liver
Fibrinogen, prothrombin, factors 5, 7, 8, 9, 10, 11, 12, 13 and tissue factor
What is the intrinsic pathway activated by?
Factors VIII, IX, XI and XII
What is the extrinsic pathway activated by?
Factor VII
Describe the process of clot formation
Activation of coagulation leads to thrombin formation. Thrombin converts fibrinogen to fibrin, which forms fibrin polymers and blocks the wound. After 24-48 hours these are changed to fibrin fragments via fibrinolysis
How are the different routes of coagulation measured?
Intrinsic is measured by APTT and extrinsic is measured by PT
What is a ‘thrombin burst’?
When lots of thrombin is produced by positive feedback of clotting factors. It converts fibrinogen to fibrin.
What is Von Willebrand factor?
It is involved with platelet adhesion to the vessel wall, platelet aggregation and also carries FVIII
What is the role of the vessel wall in haemostasis?
- first step is vasoconstriction
- production of Von Willebrands factor (essential for plt adhesion, carrier and ‘protector’ of factor 8)
- exposure of collagen and tissue factor which initiates activation of clotting factors
What do natural anticoagulants do?
These stop further coagulation, ensuring that the clot does not become too big
Give some examples of congenital coagulation factor disorders
- haemophilia A (factor 8)
- haemophilia B (factor 9)
Give some examples of acquired coagulation disorders
- liver disease
- vitamin K deficiency
- anticoagulants including warfarin (inhibits vitamin K)
Give some symptoms of coagulation factor disorders
- muscle haematomas
- recurrent haemarthroses
- joint pain and deformity
- prolonged bleeding post-dental extraction
- life threatening post-op and post-trauma bleeding
- intracerebral haemorrhage
What is haemophilia A and how is it inherited?
- congenital lack of factor VIII (varies in severity)
- X-linked recessive
- usually diagnosed in infancy (or soon after birth if family history)
- bleeding into muscles and joints
