Haemostasis Flashcards
Define haemostasis
The arrest of bleeding and the maintanence of vascular patency (clot formation)
What does haemostasis occur in response to ?
Damage to the vessel wall - it stops the bleeding and keeps the blood within the damaged vessel (maintain vascular patency)
What are the 4 main stages of haemostasis ?
- Formation of platelet plug - known as Primary Haemostasis
- Formation of fibrin clot - known as Secondary Haemostasis
- Fibrinolysis
- Anticoagulant Defences
Describe primary haemostasis
- Damage to endothelial wall occurs which causes exposure of collagen and subendothelial fibres and vasoconstriction
- The damage endothelium releases Von williebrand factor and other proteins to which platelets have receptors - platelets then adhere to the site of injury via glycoprotein 1b and VWF (this is platelet ahdesion)
- After platelet adhesion the platelet then secretes various chemicals such as ADP and thromboxane A2 and thrombin which leads aggregation and activation of more platelets (platelets are activated via ADP receptors on their surface)
- Platelets aggregate together via GPIIbIIIa and fibrinogen (at the same time as aggregation step 5 is occuring)
- Acitvated and aggregated platelets alter their shape to expose more phospholipid on the surface-provides a greater surface area for coagulation activation and fibrin production to stabilise the clot
This whole process is a positive feedback mechanism with the platelets which are recturited all carrying out the same steps and releasing more chemicals to stimulate aggregation and activation of more platelets
What are the functions of von williebrand factor ?
- Facilitates the activation and adhesion of platelets to the collagen and subendothelial fibrils (damaged vessel wall) by acting as a bridging molecule
- To bind to factor VIII, protecting it from destruction in the circulation
- To make platelets bind to eachother (aggregation)
What is the function of thromboxane A2
It stimulates activation of new platelets as well as increases platelet aggregation
What is the function of ADP ?
ADP acts on ADP receptors on other platelets to activate and recruit them to the clot formation process
What is necessary to produce thromboxane A2 from platelets ?
Cyclo-oxygenase (COX) - aspirin inhibits this
What is the normal lifespan of a platelet ?
7-10days - this is important to know in relation to anti-platelet drugs as they usually work once given for the whole duration of the lifespan of a platelet ==> when stopping antiplatelet medication it takes 7-10days for effect to ware off
What are the problems which can cause failure of primary haemostasis (platelet plug formation)?
Vascular defects
Platelet disorders:
- Reduced number (thrombocytopenia)
- Reduced function
Von williebrand factor deficiency/defective
Give some examples of vascular defects which can cause problems with formation of platelet plug (primary haemostasis)
- Senile purpura - as you get older you loose collagen from the vessel walls this results in easier bruising seen as purpura
- Congenital conditions e.g. ehler danlos syndrome where they have defective collagen
What are some of the causes for reduced number of platelets resulting in failure of primary haemostasis ?
Decreased marrow production:
- Aplastic anaemia
- Megloblastic anaemia
- Marrow infiltration - malignancy
- Marrow suppression - chemo and radio
Excessive destruction:
- Immune thrombocytopenia purpura (ITP)
- Thrombotic thrombocytopenic purpura (TTP)
What are some of the causes of reduced platelet function?
- MPD
- Antiplatlets - Aspirin, NSAID’s - have similar action to aspirin
What is the typical bleeding pattern which is suggestive of a primary haemostasis disorder ?
- Prolonged bleeding from cuts
- Spontaneous/easy bruising and purpura - bleeding into the skin, esp on the lower limb e.g. shins
- Bleeding from mucous membranes e.g. epistaxis, bleeding from gums, GI bleeding, menorrhagia (abnormally heavy menstrual bleeding), conjunctival
- Intracranial haemorrhage
- Rential haemorrhage - dont forget to check the eyes
What sign is shown and what type of bleeding disorder is this associated with ?
Purpura on the lower limb - associated with problems with primary haemostasis
Describe the stages of secondary haemostasis (fibrin clot formation)
Note this is a continuation on from primary haemostasis
Platelets are full of phospholipid which is negatively charged and calcium which is positively charged.
Platelets in the platelet plug will express positively charged calcium on their surface to attract negatively charged clotting factors
- Tissue factor (TF also called thromboplastin) is relased from damaged endothelial cells and activated platelets
- TF activates clotting factor VII into VIIa
- VIIa activates factors V and Xa
- V & Xa work together to breakdown prothrombin (factor II) into thrombin (factor IIa)
- Thrombin works in 2 ways
- It works by amplification through activating clotting factors VIII and IXa ==> VIII and IXa then activate factors V and Xa to breakdown more prothrombin into thrombin (postitive feedback loop)
- Thrombin also works to breakdown fibrinogen (factor I) into fibrin (Ia) ==> resulting in the formation of a fibrin clot
Describe the 3rd component of haemostasis - fibrinolysis
- Inactive plasminogen is converted into plasmin by tissue plasminogen activator (tPA)
- Fibrin is then brokendown by plasmin into FDP’s (fibrin degredation products)
What are the consequences of failure of fibrin clot formation (secondary haemostasis)?
No characteristic clinical syndrome but if due to single/mutliple clotting factor deficiencies then often causes delayed bleeding into muscles and joints
Pic shows bleed into a knee
