what are the principles of haemostasis?
maintains stable physiology: blood goes from liquid to solid in areas where needed
what is haemostasis a balance between
- coagulation (blood changes from liquid to gel)
- fibrinolysis (breakdown of fibrin in blood clots)
what occurs to the balance of haemostasis when thrombosis occurs?
- coagulation factors are activated
- increase in platelets which plug up the whole and allow coagulation factors to interact
- decrease in fibrinolytic factors & anticoagulant proteins
what occurs to the balance of haemostasis when there is excessive bleeding?
- increase in fibrinolytic factors & anticoagulant proteins
- decrease in coagulant factors and platelets
haemophilia
deficient in clotting factors -> excess bleeding
thrombocytopaenic
low blood platelet count
ecchymosis
symptom of most bleeding disorders
- excessive bruising: a discoloration of the skin resulting from bleeding underneath, typically caused by bruising.
primary haemostasis
Vasoconstriction (immediate) Platelet adhesion (within seconds) Platelet aggregation and contraction (within minutes)
secondary haemostasis
Activation of coagulation factors (within seconds)
Formation of fibrin (within minutes)
fibrinolysis
Activation of fibrinolysis (within minutes)
Lysis of the plug (within hours)
how are platelets drawn to area of damaged vessel?
Damage to the blood vessel -> barrier is broken -> exposes underlying very adhesive proteins e.g. collagen -> platelets recognise this & stick to the area using VWFactor
Role of VWf
Acts as an anchor to platelets
what happens when platelets adhere to a region?
Platelets change: develop increased surface area, sudopodia (can stick in neatly & perform their function)
On top of that more platelets accumulate
how are platelets attracted to collagen?
- VWF binds to extracellular collagen & GpIb-IX-V complex
- the GpIIb-III undergoes a conformational change
- structural changes in platelets
- negatively charged phospholipids: pro-coagulant surface
describe the initiation of coagulation
- cell expressing tissue factor
- forms a complex with factor 7a
- factor 7a converts 10 to 10a
- 10a joins with 5a to produce thrombin
- factor 2 leads to platelet aggregation & accumulation
- amplifies thrombin production
amplification of coagulation
Burst of thrombin: drives production of Fibrin from fibrinogen
what happens in haemostasis for someone who has haemophilia A
- deficiency of factor 8 which is why the big thrombin burst doesn’t happen
- symptoms involve bleeding just by walking
- blood in the joint is toxic
what happens in haemostasis for someone who has haemophilia B
- don’t get the thrombin burst and so there is poor blood clot
what does each reaction in the waterfall hypothesis require?
- Ca2+
- phospholipid
laboratory evaluation of bleeding
- FBC and film
- Coagulation tests
- Platelet function
- Global tests
how do we ensure that the haemostasis testing is accurate?
by ensuring the quality of the specimen submitted:
Blood is anticoagulated with 3.2 % (0.109 M) Sodium citrate
Most tubes contain 0.3 mL anticoagulant and require 2.7 mLs of blood.
what are the main principles of clotting tests?
- incubate plasma with reagents necessary for coagulation
- measure the time taken for fibrin clot to form
what is prothrombin time?
evaluates the extrinsic pathway
wait until you see the formation of yellow jelly (fibrin) 8-10 seconds
what is activated partial thromboplastin time?
evaluates the intrinsic pathway
