hemostasis and clotting cascade

Question 1

Platelets are made from?

Answer 1

megakaryocytes (150k-450k norm) by thrombopoeitin(TPO)

Question 2

TPO vs EPO

Answer 2

sim N-term, C-term has a longer half life (8-12hr)

produced in kidney/liver

Question 3

TPO does what?

Answer 3

increasing differentiation and maturation rate of hematopoietic stem cells -> more mega and platelets
increase platelet fxn

Question 4

mechanism of TPO

Answer 4

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)

Question 5

4 steps of hemostais

Answer 5

vascular spasm, form platelet plug, form blood blot, repair damage

Question 6

purpose of vasospasm?

Answer 6

upstream myogenic reflex that damaged endothilum/sm release serotonin/thromboxane A2 to cause vasoconstriction to prevent blood flow to damaged site

Question 7

what causes the right thing to bind to collagen and laminin receptors?

What is c/l purpose?

Answer 7

glycoproteins on the cell mem - neg charge that keeps other endothelial cells away

collagen and laminin link and hold platelet cells together

Question 8

adhesion of platelet together is initiated by what?

what are the ligands?

Answer 8

receptors like glycoprotein Ib/Ia (collagen, fibronectin, laminin)

von willebrand factor, collagen, fibronectin, laminin

Question 9

what activates the platelet receptors to form a plug?

what is released because of this?

What does this cause?

Answer 9

phospholipase C and Ca influx

dense granules - atp, apd, serotonin, ca

a granules - vWF, factor V, fibrinogen

adp, serotonin, ta2 promotes aggregation

Question 10

what does thromboxane A2 come from

Answer 10

arachidonic acid by cyclooxgenase

Question 11

what binds to P2Y12 and what inhibits it?

Answer 11

ADP

Plavix (clopidogrel), antiplatelet agent

Question 12

once activated what can bind?

what does this do?

Answer 12

fibrinogen

bridges platelets, plug!

Question 13

what does aspirin do

Answer 13

inhibits clot by reducing release of TA2

cyclooxygenase inhibitor

Question 14

blood clot formation

Answer 14

prothrombin -> thrombin -> fibrin + fibrin stabilizing factor + Ca (for polymerization and contraction)

Question 15

what does platelet derived grothw factor do?

Answer 15

secreted by platelets

stim fibroblast to grow and diff into sm

Question 16

how does the body get rid of clots?

Answer 16

endothitial cell Thrombomodulin/thrombin -> activates protein C -> inactivates inhibitor to t-PA (active t-PA) -> plasminogen to plasmin -> lysis fibrin and fibrinogen

Question 17

what limits clotting (anticoagulation)?

Answer 17

fibrin (inhibits thrombin)
prostacyclin (vasodil, limit aggregation)
antithrombin III (bind thrombin, anticoag)
heprin (from mast)

Question 18

what factors are dependent on vitamin k?

Answer 18

II, VII, IX, X

protein s and c

Question 19

what is the key difference bw primary and secondary hemostasis

Answer 19

primary - weak platelet plug

secondary - strong w a fibrin mesh, longer duration

Question 20

what do thrombin, TPA/Urokinase/Strepotokinase have in common?

Answer 20

proteases, cuts and cleaves

thrombin, fibrinogen -> fibrin, factor XIII is activated f+xiii makes cross linkage
t/u/s, plasminogen -> plasmin

Question 21

thrombin does waht

Answer 21

prothrom -> thrombin
V and VIII -> active forms
fibrinogen -> fibrin
activation of platelets
XIII -> XIIIa cross linked fibrin

Question 22

hydroxycoumarins? what do they do?

Answer 22

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

Question 23

why is y-glutamyl carboxylation important in vit k formation

Answer 23

oxidizes and adds (-) factors that attract the clot

Question 24

which form of warfarin is more potent in producing an anticoag response?

when is it active?

Answer 24

S-warfarin

only free warfarin is pharmacologically active

reacts with a lot of other drugs

Question 25

protein c deficiency causes what?

Answer 25

significantly increased risk of venous thrombosis

Question 26

how does protein c and s pay a role in reg anticoagulation?

Answer 26

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

Question 27

hemophilia A and b

Answer 27

factor viii def
or classic hemophilia a
more common than b
b is called factor IX def or christmas disease

Question 28

what happens without VIII in the case of hemophilia

Answer 28

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

Question 29

how can a dr gain clues to what clotting disorder a pt has?

Answer 29

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

Question 30

what happens when you havea prolonged PT, and normal PTT

Answer 30

liver disease

dec vit K, factor VIII