Coagulation Flashcards
Overall balance between clot formation and clot dissolution
clot formation
* Primary haemostasis -> immediate reaction to injury/trauma - primary haemostatic plug
* coagulation cascade
imbalance will lead to bleeding tendancy or prothrombotic tendancy
diagram to summarise haemostasis
injury ->
* vasoconstriction of blood wall (mechanical step - reduced flow -> minimise blood loss)
* plt activation -> aggregation -> primary plug
* plt aggregate provider for phospholipid component for coag cascade
main function of leucocytes in blood clot formation
provide link with the tissue factor
vasoconstriction in haemostasis
mechanical reflex
smooth muscle in subendothelail componenet of blood vessels
supported by collagen, elastin, glyosaminoglycans
How is the endothelium involved in haemostasis
Acts as a barrier between coag proteins and subendothelial tissue
* if breached -> exposure of subendothelial connective tissue -> primary haemstatic plug and coag
produce
* PGI2 (prostaglandin) part of arachidonic acid metabolism for plt function
* VWF
* plasminogen activators - involved in breakdown of clot - fibrinolysis
* thrombomodulin - receptor essential for protein C pathway
plt plug formation
subendo connective tissue exposed -> activate plts -> glued into area damaged
VWF involved -> stable plt plug
origin of plts
start from plt precursers
megakaryocyte - stepwise proliferation in bone marrow - released in circ. each produce up to 4000 plts
plt lifespan 10days
governed by thrompoietic factors - thrombopoietin, interleukins 6 and 12
can use these if person has low plts
when will you see the effect of stopping anti-plts
eg aspirin/clopidogrel
10 days - because paralyse plts for rest of lifespan (10days)
so have to stop 7-10days before surgery
features of plts
glycoprotein as receptors - communication channel where interact with other plts, endothelium, VWF
dense granules - contain energy providing units
alpha granules - contain growth factors, fibrinogen and factor 5
open cannalicular system and microtubules and actomyosin - provide surface area when activated
Mech of plt plug formation
- subendo exposed
- plt adhere to glycoprotein 1b with assistance from VWF or directly through glycoprotein 1a
- release of ADP and thromboxane a2
- plt aggregation - through glycoprotein IIbIIIa (ie fibrinogen receptor)
presentation of VWF deficiency
present like dont have plts - because of lack of plt adhesion
first thing given in suspected MI
aspirin - to give an antiplt effect
production of PGI2 and thromboxane A2
metabolism of arachidonic acid
under cyclo-oxygenase enzymes (COX)
Mechanism of aspirin
block COX irreversibly
mech of NSAIDs
block COX
reversible - so effect on plts only last for transient period
Main pathways of plt activation
arachidonic acid metabolism
ADP receptors - clopidogrel target this
summarise clot formation
intrinsic pathway
extrinsic - activation of tissue factor and factor 7 - rate limiting factor for factor 10 so call them tenase
need phopsholipid
want prothrombin -> thrombin -> fibrinogen -> fibrinogen
amplication with each factor
thrombin formed following activation of plt plug -> activation of fibrinogen, plts. factor 5 and 8, zymogens (7 11, 13)
prothrombinanes -> activate activation of prothrombin -> thrombin -> catalyse fibrinogen (unstable monomer) into fibrin (stable polymer)
initiation phase of clot formation
- damage of epithelium
- release of TF and factor 7
- activate 9 and 10
- factor 10 with actuvated 5 - go onto next step
factor 5 leiden
commonest hereditory prothrombotic condition in caucasian
cant be involved with amplification stage
they are activated protein C resistant - factor 5 is resistant to break down by actuvted protein C because of nucleotide substitution
amplification stage of clot formation
propagation phase of clots
actuvated plts with 9 10 and 5 - result in more activation by recruitment of more activated 10 and 5 -> thrombin burst
summarise amplification
formation of thrombin generation influenced by the number of components
vit K dependent clotting factors
2 7 9 10
produced in liver
need vit K as co-enzyme for gamma carboxylase enzyme
if Vit K deficient - liver will still make the factors - they will just be inactive
why would you be vit K deficient
diet
broad spectum Abx - kill flora needed to make vit K
obstruction of biliary tract - because vit K is fat soluble required bile form intestinal biliary system
warfarin
