Haemostasis Intro Flashcards
what is haemostasis
the arrest of bleeding and the maintenance of vascular patency
what does haemostasis need to be
always ready
prompt response to reduce blood loss
localised response
protection against unwanted thrombosis
what constitutes primary homeostasis
the formation of a platelet plug
what is secondary homeostasis
the formation of a fibrin clot (more stable meshwork)
what happens after secondary haemostasis
fibrinolysis and anticoagulant defences to re-establish blood flow in the vessel
how are platelets made
bud of megakaryocytes in the bone marrow
what is the lifespan of platelets
7-10 days in the circulation (as have no nucleus)
what is the structure of platelets
small anucleate discs
how are platelets directed to a site of injury
endothelial (vessel wall) damage exposes collagen and releases von willebrand factor (+other proteins) to which platelets have receptors= bind to site of injury
platelets then secrete chemicals which auses aggregation at this site
what might cause a failure of platelet plug formation (primary haemostasis)
vascular (e.g. if collagen deficient)
platelets (reduced number- thrombocytopenia, or reduced function- e.g. on aspirin or NSAIDs)
von willebrand factor (e.g. inherited deficiency)
what can cause a collagen deficiency resulting in primary haemostasis problems
old age
scurvy (vit c needed to make collagen)
what are the potential consequences of platelet plug formation failure
spontaneous bruising and purpura
mucosal bleeding (epistaxes, GI, blood blisters in mouth, conjunctival haemorrhages, menorrhagia)
intracranial haemorrhage
retinal haemorrhages
where does purpura usually affect
lower limbs (as gravity big influence, pulls blood out of vessels)
does purpura blanch
no
why do more women with VWF deficiency present
affects men and women equally but women more likely to present with menorrhagia
what screening test for primary haemostasis
platelet count
where does the fibrin clot form
on the platelet plug surface
how does the fibrin clot form
platelets full of phospholipids which are negatively charged
platelets release calcium which is positively charged and sits on the cell surface
this attracts the clotting factors
tissue factor (CF7) attracted first which starts haemostasis and activates CF 5 and 10 (initiation phase) prothrombin activated into thrombin (by factors 5 and 10) (propagation stage) thrombin cleaves fibrinogen into fibrin
thrombin also activates CF 8 and 9 (amplification stage) which activate CF 5 and 10 creating positive feedback mechanism allowing fast clot formation
what can cause failure of fibrin clot formation (secondary haemostasis)
single clotting factor deficiency (usually hereditary e.g. haemophilia) multiple clotting factor deficiency (usually acquired e.g. DIC) increased fibrinolysis (usually part of complex coaguloplathy e.g. DIC)
which single clotting deficiencies are more common
haemophilia A (CF 8) most common haemophilia B (CF 9) less common
why do you have multiple CF deficiency in DIC
as making so many and then breaking down so many clots
how does fibrinolysis happen
plasminogen converted to plasmin by tissue plasminogen activator (tPA)
fibrin then broken down into fibrin degradation products by plasmin
what test can measure fibrin degradation products
D dimers
what are the consequences of fibrin clot formation failure (problems with secondary haemostasis)
no classic clinical syndrome
can be combined with primary haemostasis failure
pattern of bleeding depends on:
- single/ multiple factors affected (single e.g. haemophilia, affects joints in certain pattern. multiple e.g. DIC)
- the clotting factors involved
what happens to clotting factors in DIC
all used up
what screening tests for fibrin clot formation (secondary haemostasis)
prothrombin time (uses citrate to analyse factors 7, 5, 10 and thrombin) activated partial thromboplastin time (analyses factors 8 and 9 (which in turn activate 5 and 10)
e.g. if missing factor 8/0 then APTT will be increased by PT normal
how do NSAIDs affect haemostasis
interfere with platelet function affecting primary haemostasis
how do warfarin and NOAC affect haemostasis
affect secondary hameostasis
what does anti-thrombin do
neutralises thombin, tissue factor (CF 7), CF 5, 10, 8 and 9
how can you assess previous haemostasis from Hx
bleeding/ bruising duration (if lifelong) previous surgery/ dental procedure, how long were you nleeding for afterwards Drug Hx FHx exam
what is serine protease inhibitor
antithrombin- naturally occurring anti coagulant
what are protein C and protein S
naturally occurring anticoagulants
switch off CF 8 and 8
what does thrombomodulin do
modulates the function of thrombin to increase protein C and protein S which in turn deactivate CF 5 and 8, cause anti coagulation
what is thrombophilia
increased tendency to develop venous thrombosis (e.g. DVT, PE)
what can cause thrombophilia
deficiency of naturally occurring anticoagulants (serine protease inhibitors (anti thrombin), protein C and protein S (thombomodulin)
