intro to haemostasis Flashcards
what is haemostasis?
arrest of bleeding and the maintenance of vascular patency (open & unobstructed blood vessel)
what are the requirements of haemostasis?
- permanent state of readiness
- prompt response
- localised response
- protection against unwanted thrombosis (be able to switch of stopping bleeding system when no longer required)
what are the 4 components of haemostasis?
- platelets (first thing to plug the hole)
- formation of fibrin clot (blood clotting factors form meshwork)
- fibrinolysis (the break down of clot when needed)
- anticoagulant defences (proteins to prevent unwanted thrombosis)
what are platelets?
- small anucleate discs that have life cycle of 7-10 days (important to know for surgeries etc)
- they are formed in bone marrow by budding megakaryocytes and then leave bone marrow to go into blood stream (megakaryocytes last a long time but just remain in blood stream)
what is the process of primary haemostasis?
- damage to vessel wall
- endothelial damage exposes collagen and damaged endothelium releases protein Von Willebrand Factor (VWF) - VWF binds to exposed collagen
- platelet adhesion = platelets have receptors or surface glycoproteins that stick to exposed collagen fibres & each other (platelets are attracted by binding of VWF to collagen)
- platelets activation = platelets then secrete various chemicals which leads to aggregation (clumping) of platelets at site of injury to plug hole and achieve primary haemostasis
what can happen to result in failure of primary haemostasis?
- vessel wall = could be less collagen so weakened vessel wall (collagen deficiency can be through vitamin c deficiency - scurvy)
- reduced number of platelets - due to failure of production of platelets, autoimmune mediated (antibodies could stick to platelets and mean platelets get destroyed)
- reduced function of platelets - patients who are prone to developing blood blocks - get put on drugs that mean more prone to bleeding (like aspirin) - drug induced common cause of reduced function
- Von willebrand factor = there is disease that leads to lower levels or reduced function → bleeding tendency
what are
a) minor consequences of platelet plug failure?
b) severe consequences of platelet plug failure?
a) spontaneous bruising and purpura (fine bruising under skin - looks like rash, if glass on top then won’t disappear) - often more likely to see on lower limbs OR mucosal bleeding (epistaxes, GI, conjunctival, menorrhagia (can have heavy periods))
b) intracranial hemorrhage or retinal hemorrhage
what happens in secondary haemostasis?
- platelets are blood fragments with a negatively charged phospholipid surface
- when platelets activated - they release Ca2+ into their surroundings
- clotting factors in the blood (proteins involved in coagulation cascade) are negatively charged so therefore bind to positively charged surface of activated platelets (what brings localised response)
- TF (tissue factor), also known as thromboplastin released from damaged tissue
- TF forms complex with factor VII, initiating activation of coagulation cascade
- thrombin is generated through complex from prothrombin and then converts soluble fibrinogen → insoluble fibrin and also activates factors to make more thrombin and clotting factors so acts as positive feedback loop so very rapidly (efficient) system to make fibrin clot
what is propagation phase?
amplification of clotting process, is referring to the positive feedback loop where thrombin activates more coagulation factors leading to cascade effect that rapidly increases fibrin formation
what are causes of failure of fibrin clot?
- single clotting factor deficiency (usually hereditary) e.g. haemophilia
- multiple clotting factor deficiency - usually acquires (usually used up through sepsis or wide spread tissue damage) e.g. disseminated intravascular coagulation
- increased fibrinolysis (being broken down too much)
what is process of fibrinolysis?
- plasminogen converted to plasmin by tissue plasminogen activator (tPA)
- plasmin converts fibrin to fibrin degradation products (FDP’s)
what can people with big blood clots be given to break down the clots?
infusions of plasmin
what are the consequences of failure of fibrin clot formation?
- No characteristic clinical syndrome
- May be combined primary/secondary haemostatic failure
- Pattern of bleeding depends on
- Single/multiple abnormalities
- The clotting factors involved
= often get repeated bleeding in same joint
what are some naturally occurring anti-coagulants?
serine protease inhibitors:
1. anti-thrombin
2. protein C and protein S
how does anti thrombin work? (naturally occurring anti-coagulant)
binds and switches off thrombin (also switches off some other coagulation factors) - thrombin generation fibrin clot also involved in positive feedback of 8 & 9 so turning off thrombin turns of haemostasis nicely
