hemostasis and clotting cascade Flashcards
Platelets are made from?
megakaryocytes (150k-450k norm) by thrombopoeitin(TPO)
TPO vs EPO
sim N-term, C-term has a longer half life (8-12hr)
produced in kidney/liver
TPO does what?
increasing differentiation and maturation rate of hematopoietic stem cells -> more mega and platelets
increase platelet fxn
mechanism of TPO
binds to c-MPL rec (CD-110) on mega/plt
more bound = high numba of platelets, bc they don’t need anymore platelets made, little tpo is free (degraded)
4 steps of hemostais
vascular spasm, form platelet plug, form blood blot, repair damage
purpose of vasospasm?
upstream myogenic reflex that damaged endothilum/sm release serotonin/thromboxane A2 to cause vasoconstriction to prevent blood flow to damaged site
what causes the right thing to bind to collagen and laminin receptors?
What is c/l purpose?
glycoproteins on the cell mem - neg charge that keeps other endothelial cells away
collagen and laminin link and hold platelet cells together
adhesion of platelet together is initiated by what?
what are the ligands?
receptors like glycoprotein Ib/Ia (collagen, fibronectin, laminin)
von willebrand factor, collagen, fibronectin, laminin
what activates the platelet receptors to form a plug?
what is released because of this?
What does this cause?
phospholipase C and Ca influx
dense granules - atp, apd, serotonin, ca
a granules - vWF, factor V, fibrinogen
adp, serotonin, ta2 promotes aggregation
what does thromboxane A2 come from
arachidonic acid by cyclooxgenase
what binds to P2Y12 and what inhibits it?
ADP
Plavix (clopidogrel), antiplatelet agent
once activated what can bind?
what does this do?
fibrinogen
bridges platelets, plug!
what does aspirin do
inhibits clot by reducing release of TA2
cyclooxygenase inhibitor
blood clot formation
prothrombin -> thrombin -> fibrin + fibrin stabilizing factor + Ca (for polymerization and contraction)
what does platelet derived grothw factor do?
secreted by platelets
stim fibroblast to grow and diff into sm
how does the body get rid of clots?
endothitial cell Thrombomodulin/thrombin -> activates protein C -> inactivates inhibitor to t-PA (active t-PA) -> plasminogen to plasmin -> lysis fibrin and fibrinogen
what limits clotting (anticoagulation)?
fibrin (inhibits thrombin)
prostacyclin (vasodil, limit aggregation)
antithrombin III (bind thrombin, anticoag)
heprin (from mast)
what factors are dependent on vitamin k?
II, VII, IX, X
protein s and c
what is the key difference bw primary and secondary hemostasis
primary - weak platelet plug
secondary - strong w a fibrin mesh, longer duration
what do thrombin, TPA/Urokinase/Strepotokinase have in common?
proteases, cuts and cleaves
thrombin, fibrinogen -> fibrin, factor XIII is activated f+xiii makes cross linkage
t/u/s, plasminogen -> plasmin
thrombin does waht
prothrom -> thrombin V and VIII -> active forms fibrinogen -> fibrin activation of platelets XIII -> XIIIa cross linked fibrin
hydroxycoumarins? what do they do?
warfrain or coumadin
inhibit action of vit k
decreases activ of vit k dependent epoxide reductase (VITAMIN K 2,3-EPOXIDE REDUCTASE)
lengthen the time it takes for a clot to form
why is y-glutamyl carboxylation important in vit k formation
oxidizes and adds (-) factors that attract the clot
which form of warfarin is more potent in producing an anticoag response?
when is it active?
S-warfarin
only free warfarin is pharmacologically active
reacts with a lot of other drugs
protein c deficiency causes what?
significantly increased risk of venous thrombosis
how does protein c and s pay a role in reg anticoagulation?
proteolytically inactivate factor Va and factor VIIIa
which stops this below:
viii makes tenase which then Va comes in and makes prothrombinase to make thrombin
hemophilia A and b
factor viii def
or classic hemophilia a
more common than b
b is called factor IX def or christmas disease
what happens without VIII in the case of hemophilia
viii makes tenase which then Va and Xa comes in and makes prothrombinase to make thrombin
thrombin is reduced! can’t help to activate X
how can a dr gain clues to what clotting disorder a pt has?
Prothrombin time - I, ii, v, vii, x (fibrnogen) = EXTRINSIC
partial thromboplastin time - xiii, xi ,ix, viii, x, v, II (prothrom), I (fibrinogen), prekallikrein, high mol weight kiniogen = INSTRINSIC AND COMMON CLOT
what happens when you havea prolonged PT, and normal PTT
liver disease
dec vit K, factor VIII
