Clotting & Blood flow I&II

Question 1

can platelet activation alone stop a large bleed?

Answer 1

no - need help from activation of coagulation cascade

Question 2

role of fibrinolysis

Answer 2

removes the blood clot to restore blood flow to the repaired blood vessel

Question 3

collagen

Answer 3

plays a role in platelet aggregation and activation

-normally hidden under endothelial lining

Question 4

hemostasis

Answer 4

prevents blood loss from broken blood vessel

• primary –> vascular spasm, platelet plug
• secondary –> blood coagulation (clotting)

Question 5

platelets

Answer 5

formed from megakaryocytes in bone marrow

• no nuclei, have mitochondria for ATP
• removed by tissue macrophages

Question 6

prostacyclin (PGI2) and NO

Answer 6

inhibit platelet activation and aggregation

• inhibited by COX2
• vasodilate to increase laminar blood flow or directly prevent platelet aggregation

Question 7

heparan sulfate

Answer 7

activate antithrombin preventing blood clot

Question 8

thrombomodulin

Answer 8

inhibit thrombin activation preventing coagulation

Question 9

tissue factor inhibitor

Answer 9

inhibit tissue factors preventing coagulation

Question 10

2 ways to inhibit platelet aggregation?

Answer 10

1. endothelial integrity - collagen hidden

2. laminar flow by PGI2 and NO

Question 11

role of ADP in platelet aggregation

Answer 11

needed for aggregation

• ectonucleotidases –> break nucleotides –> no ADP or platelet aggregation
• adenosine –> compete w/ ADP binding spot –> inhibit aggregation

Question 12

GP 1b-5-6

Answer 12

receptor on platelet - binds to vWF attached to collagen

-do not recognize free vWF

Question 13

GP 1a/2a and GP 6

Answer 13

bind collagen directly

-target for therapy

Question 14

GP 2b/3a

Answer 14

most important - cannot be active all the time

-bind FREE vWF and fibrinogen to begin platelet aggregation

Question 15

thromboxane A2

Answer 15

secreted from activated platelets but also activates platelets (+ feedback)
-made from COX –> NSAIDs inhibit synthesis and coagulation

Question 16

alpha vs. dense granules

Answer 16

release contents when platelets are activated

• alpha = release fibrinogen, vWF, coagulation factor 5
• dense = release ADP, Ca++

Question 17

von willebrand factor

Answer 17

made in multimers

• deficient in ADAMTS13 –> outoaggregation of platelets leading to thrombosis and thrombotic thrombocytopenia purpura (TTP)
• binds collagen for GP 1a-5-9
• increase half life of factor 8

Question 18

Ca++ during platelet activation

Answer 18

activation increases Ca++ levels –> myosin/actin interaction –> filopodial shape to clot easier and increase SA for binding
-do not coagulate without Ca++

Question 19

what results in the binding of ADP (to P2Y receptor) or thromboxane A2?

Answer 19

activate GP 2b/3a –> bind fibrinogen and vWF –> meshwork for platelet aggregation (platelet plug)
-GP 2b/3a inactive form until needed

Question 20

role of fibrinogen

Answer 20

connects the platelets together forming a weak plug

-GP 2b/3a binds the free fibrinogen and vWF to aggregate the platelets - does not need collagen

Question 21

what is the goal of coagulation cascade?

Answer 21

convert fibrinogen to fibrin and cross-link to make stronger

• classical (intrinsic and extrinsic)
• contemporary

Question 22

which factor combines with 11a to break 10 to 10a?

Answer 22

factor 8a

-8a + 11a forms intrinsic X-ase

Question 23

which factor combines with 10a converting prothrombin to thrombin?

Answer 23

5a

5a + 10a forms prothrombin complex

Question 24

what combines with tissue factor in extrinsic pathway?

Answer 24

7a

TF + 7a forms extrinsic X-ase which breaks 10 to 10a

Question 25

hemophilia

Answer 25

occurs with tissue factor mutation | -cannot do intrinsic or extrinsic pathways --> no coagulation

Question 26

what is required for platelet aggregation interconnecting with coagulation cascade?

Answer 26

- neg charge surface on platelets from phospholipids | - Ca2+ for linking together

Question 27

role of thrombin

Answer 27

- covert fibrinogen to fibrin - activate tissue factor 13 to cross link fibrin (strong) - also activate tissue factor 5,8,11 - activates intrinsic mechanism

Question 28

what forms intrinsic tenase (Xase)?

Answer 28

factor 9a and 8a | -activate 10a

Question 29

what forms extrinsic tenase (Xase)?

Answer 29

tissue factor and 7a (factor 3) | -activate 10a

Question 30

what forms prothrombinase?

Answer 30

factor 10a and 5a | -convert prothrombin to thrombin

Question 31

contemporary model

Answer 31

-extrinsic (initiation) activates intrinsic (amplification) after producing thrombin

Question 32

what does thrombin activate in the contemporary pathway?

Answer 32

- 11 --> 11a - 8 --> 8a combining with 9a (intrinsic Xase) - 5 --> 5a - increase platelet activation, fibrinogen, vWF

Question 33

difference b/w contemporary and classical model

Answer 33

- contemporary - form thrombin 1st through extrinsic model then activate intrinsic - classical - do not need thrombin to activate intrinsic (have factor 12)

Question 34

protein C

Answer 34

thrombin inhibition - thrombomodulin (endothelium) binds with thrombin --> activate protein C --> inactivate 5a and 8a - requires protein S cofactor

Question 35

antithrombin

Answer 35

normal endothelium | -bind to heparan sulfate to inactivate thrombin, 9a, 10a, 11a --> stop coagulation

Question 36

tissue factor pathway inhibitor

Answer 36

normal endothelium | -inhibit 10a and 12a tissue factor complex --> stop coagulation

Question 37

role of Ca2+ in coagulation

Answer 37

- platelet aggregation, change shape, and forming complexes | - hemophilia with hypocalcemia

Question 38

role of vitamin K in coagulation

Answer 38

coenzyme for synthesis for clotting factors - deficiency --> bleeding - warfarin can inhibit recycling

Question 39

role of plasmin

Answer 39

degrades the blood clot by chewing off fibrin --> forms D dimers (high levels in DVT) -recombinant plasminogen activators to prevent blood clots

Question 40

petechiae

Answer 40

common platelet deficiency, not common coagulation deficiency -platelet aggregation stops the bleeding for leaky capillary

Question 41

thrombocytopenia vs. thrombocytosis

Answer 41

``` thrombocytopenia = bleeding tendency thrombocytosis = coagulation tendency ```

Question 42

prothrombin time

Answer 42

tissue factor + phospholipids + Ca2+ - INR - standardization of plasma to see how good tissue factor is working - fast coagulation - use if on warfarin or suspected vit. K deficiency

Question 43

partial prothrombin time

Answer 43

phospholipids + Ca2+ + silica - no tissue factor or standardization --> rely on intrinsic pathway - slower coagulation