Blood Coagulation and Wound Healing

Question 1

what are the steps to blood clotting (coagulation)

Answer 1

-injury or damage
- vessel contracts
- platelet plug
-fibrin clot

Question 2

what happens in primary hemostasis

Answer 2

-vasoconstriction and platelet response
-platelet aggregation at the site of injury is mediated by platelet receptors, platelet derived agonists, platelet derived adhesive proteins and plasma derived adhesive proteins

Question 3

what happens in secondary hemostasis

Answer 3

• clotting cascade
• coagulation of serine proteases that results in cleavage of soluble fibrinogen by thrombin. thrombin cleavage generates insoluble fibrin that forms a cross-linked fibrin mesh at the sit of injury

Question 4

when does fibrin generation occur

Answer 4

simultaneously to platelet aggregation

Question 5

what happens when platelets bind to collagen

Answer 5

-undergo a release reaction where they secrete ADP, serotonin, and TXA2.
-serotonin and TXA2 cause vasoconstriction
-ADP and TXA2 attract platelets and make them stick to the collagen in the broken vessel to make the platelet plug

Question 6

why is calcium important

Answer 6

clotting cascade cant take place without it

Question 7

what does serotonin come from

Answer 7

tryptophan

Question 8

what is serotonin secreted by

Answer 8

enterochromaffin cells

Question 9

how are platelets formed

Answer 9

arachindonic acid is converted into endoperoxides by cyclooxygenase (prostaglandin synthase) which then gets converted into TXA2 by thromboxane synthetase which gets converted into plateletes (TXAB2)

Question 10

how are endothelial cells formed

Answer 10

arachindonic acid is converted into endoperoxides by cyclooxygenase (prostaglandin synthase) which then gets converted into prostacylin by prostacyclin synthase which gets converted into 6 keto PGF 1 alpha (endothelial cells)

Question 11

what is the initial binding of platelets to vWF mediated by

Answer 11

glycoproteins that are necessary for platelet tethering (GPIIb/IIIa) but dont promote strong adhesion

Question 12

what is responsible for firm adhesion of platelets to the subendothelia

Answer 12

GPIIb/IIIa

Question 13

what happens to GBIIb/IIIa upon platelet activation

Answer 13

GBIIb/IIIa undergoes a conformational change that reveals a binding site for vWF or fibrinogen. vWF binds at the subendothelial surface to promote strong adhesion to the vessel wall

Question 14

what is the delay in platelet activation

Answer 14

platelets activate before releasing ADP

Question 15

what do aggregometer tracings do

Answer 15

record the aggregation of platelets in platelet rich plasma in response to an aggregation agent

Question 16

how does ADP affect platelet aggregation

Answer 16

the higher the ADP the longer it can sustain platelet aggregation

Question 17

what is the extrinsic pathway activated by

Answer 17

external trauma that causes blood to escape from the vascular system

Question 18

what factor is involved in the extrinsic pathway

Answer 18

factor 7

Question 19

which pathway is the clotting cascade is quicker

Answer 19

the extrinsic

Question 20

what is the intrinsic pathway activated by

Answer 20

trauma inside the vascular system activated by platelets, exposed endothelium, chemicals, or collagen

Question 21

what factors are involved in the intrinsic pathway

Answer 21

factors 12, 11, and 9

Question 22

which pathway is the clotting cascade is more important

Answer 22

the intrinsic pathway

Question 23

what factors does the common pathway involve

Answer 23

factors 1,2 5, and 10

Question 24

what does activated partial thromboplastin time test measure

Answer 24

the intrinsic pathway

Question 25

what does the prothrombin time test measure

Answer 25

extrinsic pathway

Question 26

what are the fat soluble vitamins

Answer 26

- vitamin D - vitamin E - vitamin A - vitamin K

Question 27

what are the vitamin K dependent factors

Answer 27

2, 7, 9, and 10

Question 28

what does the fibrin mesh do

Answer 28

laid down to reinforce and strengthen the platelet plug since thats not strong enough itself to prevent further bleeding

Question 29

what catalyzes the crosslinking of fibrin

Answer 29

transglutaminase or factor 7

Question 30

where are peptide bonds formed

Answer 30

between lysine and glutamine domains of fibrin molecules by transglutaminase

Question 31

how does fibrin polymerization and breakdown occur

Answer 31

plasmin breaks peptide bonds and destroys mesh

Question 32

what is plasmin derived from

Answer 32

plasminogen

Question 33

what converts plasminogen to plasmin

Answer 33

tissue plasminogen activator and urokinase, factor 11a, 12a, and kallikrein

Question 34

what is wound healing

Answer 34

complex process in which skin or other tissue repairs itself after injury

Question 35

what are the 4 phases of wound healing

Answer 35

-hemostasis - inflammatory -proliferative -remodeling

Question 36

what happens in hemostasis

Answer 36

within minutes post-injury, platelets aggregate at the injury site to form a fibrin clot which acts to control bleeding

Question 37

what happens in inflammatory phase

Answer 37

bacteria and debris are phagocytosed and removed from the wound site, factors are released that cause migration and division of cells involved in the proliferative phase

Question 38

what happens in the proliferative phase

Answer 38

angiogenesis, collagen deposition, granulation, tissue formation, epithelialization and wound contraction

Question 39

what happens in the remodeling phase

Answer 39

collagen is remodeled and realigned along tension force lines and cells no longer needed are removed by apoptosis

Question 40

what cells are involved in coagulation

Answer 40

platelet/fibrin deposition

Question 41

what cells are involved in the inflammatory phase

Answer 41

neutrophil, monocyte, macrophage

Question 42

what cells are involved in the proliferation phase

Answer 42

-fibroblast/collagen deposition -endothelial cell/angiogenesis - keratinocyte/re-epithelialization

Question 43

what is the plasma form of fibronectin secreted by and what does it do

Answer 43

secreted by hepatocytes and modulates platelet function

Question 44

what is the cellular form of fibronectin secreted by and what does it do

Answer 44

secreted by cells as part of the ECM and functions as a scaffold protein

Question 45

what is ACD anticoagulant

Answer 45

acid citrate dextrose solution- solution of citric acid, sodium citrate and dextrose in water

Question 46

how does citrate work as an anticoagulant

Answer 46

citrate in the form of sodium citrate or acid-citrate dextrose is used to disrupt the coagulation cascade and prevent clotting. they bind to the calcium in blood, thus no regulation of binding and cascade cannot begin

Question 47

what is the prothrombin time test used for

Answer 47

to help detect and diagnose a bleeding disorder or excessive clotting disorder.

Question 48

what is the INR calculated from and what does it measure

Answer 48

calculated from a prothrombin time test and used to monitor how well the blood thinning medication, warfarin, is working to prevent blood coagulation

Question 49

what does the prothrombin time measure

Answer 49

the integrity of the extrinsic pathway and final common pathways of the coagulation cascade. consists of tissue factor and factors 7,2,5,10, and fibrinogen

Question 50

what is prothrombin time measured in

Answer 50

seconds

Question 51

why is the INR an important tool

Answer 51

is allows for easier comparisons of test results from different labs

Question 52

what is a healthy INR

Answer 52

1.1 or below

Question 53

what is an effective therapeutic range of INR for people taking warfarin

Answer 53

2.0-3.0

Question 54

what does a higher INR mean

Answer 54

blood clots more slowly than desired

Question 55

how does warfarin work

Answer 55

competetively inhibits the vitamin K epoxide reductase complex 1 - depletes vitamin K reserves and reduced the synthesis of active clotting factors 2,7,9, and 10, coagulation regulatory factors protein C and protein S

Question 56

how can effects of warfarin be neutralized

Answer 56

massive doses of vitamin K

Question 57

what targets factor 10a

Answer 57

rivaroxaban (xarelto, eliquis)

Question 58

what targets thrombin

Answer 58

dabigatran etexilate (pradaxa)

Question 59

what are hemophilia A and B caused by

Answer 59

an X-linked recessive genetic mutation

Question 60

what is hemophilia A caused by and how do you treat it

Answer 60

caused by decreased synthesis of factor 8 and treat with recombinant factor 8

Question 61

what is hemophilia B caused by and how do you treat it

Answer 61

caused by decreased synthesis of factor 9 and treat with recombinant factor 9

Question 62

what form of hemophilia is X-mas disease

Answer 62

hemophilia B