31: Hemostasis - Wilson Flashcards Preview

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Flashcards in 31: Hemostasis - Wilson Deck (38):
1


define hemostasis

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

2

immediately following injury local factors such as endothelin trigger...

localized vasoconstriction

reduces blood flow to injured area

3

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

hemostatic plug forms

4

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

coagulation cascade

ultimately results in activation of thrombin

5

thrombin cleaves soluble _____ to yield insoluble ___

fibrinogen; fibrin

fibrin network forms, recruiting additional platelets and stabilizing the clot

6

anucleate cell fragments derived from megakaryocytes in bone marrow

platelets

7

___________ produce VWF which is secreted into subendothelial extracellular matrix

endothelial cells

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

8

efficient platelet adhesion to ECM requires _____ and ________

vWF and glycoprtn Ib on platelet membrane

9

_______ interaction required to withstand high shear forces

GPIb-vWF

10

adhesion triggers __ signal and platelets undergo dramatic shape change

calcium

become spiny, extend long processes

11

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

ADP, ATP, Ca2_ histamine, 5HT, Epi

fibrinogen, fibronectin, vWF, coagulation factor V, PDFG


12

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

prostaglandin G2

ultimately gives rise to thromboxane A2

13

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

thromboxane A2
serotonin
epinephrine

14

feed-forward activation effect of clot formation

ADP and thromboxane A2

15

____ triggers change in conformation of GpIIb-GPIIIa

ADP

allows receptor to bidn fibrinogen

16

*most common inherited bleeding disorder

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)

17

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

bernard-soulier syndrome

therapy aims to reduce bleeding risk, platelet transfusion

18

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

glanzmann thrombasthenia

therapy aims to reduce bleeding risk, platelet transfusion

19

partial thromboplastin time test measures

intrinsic pathway of coagulation cascade

20

prothrombin time test measures what

extrinsic pathway of coagulation cascade

21

intrinsic and extrinsic pathways converge upon ...

activation of factor X

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

22

factor =
I
II
III
IV
VI

fibrinogen
prothrombin
tissue factor
calcium
does not exist

23

most coagulation factors are made...

in the liver

factor VIII is made in endothelial cells

24

what coagulation factors require vit K?

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

25

warfarin MOA

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

26

key regulator of homeostasis

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)

27

where does the intrinsic pathway work?

on surface of endothelial cells

28

4 actions of thrombin

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

29

deficiency in factor VIII

hemophilia A

30

deficiency in factor IX

hemophilia B

31

endogenous anticoagulant activities

thrombin
prtn C and prtn s
serpins
tissue factor pathway inhibitor

32

thrombin both _____ and inhibits coagulation

drives

33

thrombin/thrombodmodulin activates _____

prtn C

active prtn C binds prtn S

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

34

factor V resistant to cleavage by prtn C

factor V leiden

hypercoagulation

35

antithrombin III is an example of...

serpin (serine protease inhibtiors)

inhibits thrombins and binds heparin

36

inhibitor of factor VIIa that blocks the extrinsic pathway

tissue factor pathway inhibitor TFPI

also inhibits factor Xa

prtn produced by endothelial cells

37

fibrin is degraded by ______

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)

38

how does streptokinase work?

exogenous activator of plasminogen

used to treat PE, DVT