Intro to Haemostasis Flashcards
what is haemostasis?
arrest of bleeding and maintenance of vascular patency
requirements of haemostasis?
permanent state of readiness
prompt response
localised response
protection against unwanted thrombosis
components of normal haemostatic system?
formation of platelet plug (primary haemostasis)
formation of fibrin clot (2ndary haemostasis)
fibrinolysis
anticoagulant defences (once body recognises you’ve stopped bleeding)
how are platelets formed?
in the bone marrow via budding from megakaryocytes
where are megakaryocytes found?
only in the bone marrow
do platelets have a nucleus?
no
lifespan of platelets?
7-10 days
therefore told to stop anti-platelets a week before surgery etc
how do platelets aggregate at site of injury?
endothelial damage exposes collagen and releases von Willebrand factor and other proteins to which platelets have receptors
platelet adhesion then takes place at site of injury
there is then secretion of various chemicals from the platelets which signal to other platelets and surface receptors causing aggregation of platelets at site of injury (platelet plug)
what can cause the formation of a platelet plug?
vascular (lack of collagen in vessels - age, scurvy etc)
platelets (reduced number or reduced function - aspirin, NSAIDs ets)
von Willebrand factor (inherited deficiency)
senile purpura?
easy bruising in elderly due to fragile vessel walls which rupture easily
consequences of failure to form a platelet plug?
spontaneous bruising and purpura
mucosal bleeding
intracranial haemorrhage
retinal haemorrhages
purpura is most visible on lower limb, why?
more pressure in vessels in lower limbs from walking around due to gravity
does purpura blanche?
no
presentations of mucosal bleeding?
epistaxis
GI
conjunctival
menorrhagia
screening for primary haemostasis?
platelet count
no simple screening test for other components of primary haemostasis
where does a fibrin clot occur?
on top of platelet plug
platelets full of phospholipids which are what?
-ve charge
granules released from platelets are +ve so bind to -ve phospholipids
what are the 3 parts of the sequence of fibrin clot formation?
initiation
propagation
amplification
describe initiation phase of fibrin clot formation?
endothelial damage > Tissue factor (TF) released > Clotting factor (CF) 7 activated > activates CF 5 and 10
describe propagation phase of fibrin clot formation?
activated CF5 and CF10 activates CF2 (prothrombin) to form CF2A (thrombin) > thrombin cleaves fibrinogen to form fibrin clot
describe the amplification phase of fibrin clot formation?
once thrombin is generated, some feeds back and activates CF8 and 9
CF8 and CF9 activate more CF5 and CF10 which produces more thrombin therefore amplifying the system and producing a lot of fibrin from small damage
cause of a single clotting factor deficiency?
usually CF 8 or 9 (lose amplification part so little thrombin formed)
= haemophilia
A = CF8
B = CF9 missing
causes of multiple clotting factor deficiency?
usually acquired (tissue damage from trauma/ wrong blood/liver damage > lots of TF > lots of clots > lots of clot breakdown > CFs all used up) disseminated intravascular coagulation (CFs broken down as soon as their made so used up)
causes of increased fibrinolysis?
usually part of complex coagulopathy
fibrinolysis?
breakdown of fibrin to FDPs (fibrin degeneration products)
how does fibrinolysis occur?
tissue plasminogen activator (tPA) converts plasminogen > plasmin
plasmin breaks down fibrin > FDPs
how can fibrinolysis be measured?
measure FDPs in blood
(D-Dimer test)
- can help in diagnosis of disseminated intravascular coagulation, DVT/PE etc
consequences of failure of fibrin clot formation?
no characteristic clinical syndrome
may be combined primary/secondary haemostatic failure
pattern of bleeding depends on whether single/multiple abnormalities and the clotting factors involved
screening test for fibrin clot formation via CF 7?
FBC collected in citrate (contains specific amount of anticoagulant)
fill blood to the line so anticoagulant is correct
blood is spun and platelets removed (containing phospholipids)
citrate neutralised with calcium and start haemostasis in left over plasma via TF and phospholipids (thromboplastin) and time how long it takes to clot
= prothrombin time
how are CFs 8 and 9 measured?
activated partial thromboplastin test
contact activator rather than thromboplastin added which activates 8 and 9 and time to clot is measured
naturally occurring anticoagulants?
anti-thrombin (serine protease inhibitors?)
protein C (and its cofactor protein S)
- bind to and inactivate CF 5 and 8
what is thrombophilia?
deficiency of naturally occurring anticoagulants
can be hereditary
increased tendency to develop DVT/PE
