31: Hemostasis - Wilson

Question 1

define hemostasis

Answer 1

processes preventing blood loss at sites of vascular injury whilst maintaining the fluid state of circulating blood

tightly controlled to prevent excessive bleeding and hypercoagulability

Question 2

immediately following injury local factors such as endothelin trigger…

Answer 2

localized vasoconstriction

reduces blood flow to injured area

Question 3

vascular damage exposes components of extracellular matrix, platelets adhere and activate –>

Answer 3

hemostatic plug forms

Question 4

exposure of tissue factor at site of damage sets in motion the …

Answer 4

coagulation cascade

ultimately results in activation of thrombin

Question 5

thrombin cleaves soluble _____ to yield insoluble ___

Answer 5

fibrinogen; fibrin

fibrin network forms, recruiting additional platelets and stabilizing the clot

Question 6

anucleate cell fragments derived from megakaryocytes in bone marrow

Answer 6

platelets

Question 7

___________ produce VWF which is secreted into subendothelial extracellular matrix

Answer 7

endothelial cells

vWF links platelets to collagen of the ECM; vWF also binds coagulation factor referred to as factor VIII

Question 8

efficient platelet adhesion to ECM requires _____ and ________

Answer 8

vWF and glycoprtn Ib on platelet membrane

Question 9

_______ interaction required to withstand high shear forces

Answer 9

GPIb-vWF

Question 10

adhesion triggers __ signal and platelets undergo dramatic shape change

Answer 10

calcium

become spiny, extend long processes

Question 11

activated platelets release mutliple compounds: dense (___________) and a-granules (___________)

Answer 11

ADP, ATP, Ca2_ histamine, 5HT, Epi

fibrinogen, fibronectin, vWF, coagulation factor V, PDFG

Question 12

platelt activation release free arachidonic acids, which is converted to ______ by COX

Answer 12

prostaglandin G2

ultimately gives rise to thromboxane A2

Question 13

____, ______, _____ function as vasoconstriction reducing blood loss at site of injury

Answer 13

thromboxane A2
serotonin
epinephrine

Question 14

feed-forward activation effect of clot formation

Answer 14

ADP and thromboxane A2

Question 15

____ triggers change in conformation of GpIIb-GPIIIa

Answer 15

ADP

allows receptor to bidn fibrinogen

Question 16

*most common inherited bleeding disorder

Answer 16

von Willebrand disease

sx: frequent nosebleeds, excessive bleeding following dental treatment, excessive bruising

managed with desmopressin (induces release of vSF and factor VIII form storage sites within the endothelium)

Question 17

giant platelets fail to aggregate in response to stimuli, defect in interaction between vWF and GpIb

Answer 17

bernard-soulier syndrome

therapy aims to reduce bleeding risk, platelet transfusion

Question 18

defects in gpIIb and/or GpIIIa causing platelts fail toaggregate in response to various stimuli

Answer 18

glanzmann thrombasthenia

therapy aims to reduce bleeding risk, platelet transfusion

Question 19

partial thromboplastin time test measures

Answer 19

intrinsic pathway of coagulation cascade

Question 20

prothrombin time test measures what

Answer 20

extrinsic pathway of coagulation cascade

Question 21

intrinsic and extrinsic pathways converge upon …

Answer 21

activation of factor X

factor X activation results in activation of thrombin (key regulator of coagulation)

Question 22

factor =
I
II
III
IV
VI

Answer 22

fibrinogen
prothrombin
tissue factor 
calcium
does not exist

Question 23

most coagulation factors are made…

Answer 23

in the liver

factor VIII is made in endothelial cells

Question 24

what coagulation factors require vit K?

Answer 24

prothrombin, VII, IX, X

all contain gamma-carboxygluatamate residues, which chelated Ca2+, bound attahces to negatively charged membrane lipids

restricts clot formation to site of injury! !

carboxylase conerting glutamate to gamma-carboxyglutamate requires vit K

Question 25

warfarin MOA

Answer 25

prevents regeneration of vit K (blocks production of gamma-carboxyglutamate residues)

Question 26

key regulator of homeostasis

Answer 26

thrombin

does three things

1. cleaves fibrinogen to fibrin to make clot
2. activates factor V and VII (extrinsic pathway)
3. activates factor VIII (intrinsic pathway)

Question 27

where does the intrinsic pathway work?

Answer 27

on surface of endothelial cells

Question 28

4 actions of thrombin

Answer 28

1. cleaves fibrinogen to form fibrin
2. enhances clotting via positive feedback
3. induces paltelt aggregation
4. activates endothelial cells to promote wound healing

Question 29

deficiency in factor VIII

Answer 29

hemophilia A

Question 30

deficiency in factor IX

Answer 30

hemophilia B

Question 31

endogenous anticoagulant activities

Answer 31

thrombin
prtn C and prtn s
serpins
tissue factor pathway inhibitor

Question 32

thrombin both _____ and inhibits coagulation

Answer 32

drives

Question 33

thrombin/thrombodmodulin activates _____

Answer 33

prtn C

active prtn C binds prtn S

prtn c/S complex degrades factor Va and VIIIa –> blocks clotting

Question 34

factor V resistant to cleavage by prtn C

Answer 34

factor V leiden

hypercoagulation

Question 35

antithrombin III is an example of…

Answer 35

serpin (serine protease inhibtiors)

inhibits thrombins and binds heparin

Question 36

inhibitor of factor VIIa that blocks the extrinsic pathway

Answer 36

tissue factor pathway inhibitor TFPI

also inhibits factor Xa

prtn produced by endothelial cells

Question 37

fibrin is degraded by ______

Answer 37

plasmin

plasmin circulates in blood as plasminogen, has affinity for fibrin and incorporates itself int clot

tPA secreted by endothelial cells (Stimulated by activated prtn C)

Question 38

how does streptokinase work?

Answer 38

exogenous activator of plasminogen

used to treat PE, DVT