Blood surface interactions part 2

Question 1

Identify the 5 key blood cell types involved in the response to ECC

Answer 1

 Platelets  Neutrophils  Monocytes  Lymphocytes  Endothelial Cells

Question 2

what causes Platelet Initial / Early Activation (4 things)

Answer 2

 Surface contact with ECC
 Heparin increases sensitivity
 Circulating thrombin is a powerful agonist and probably initial activator
 Platelet-activating factor (PAF)

Question 3

what causes Platelets Late Activation (7 things)

Answer 3

 Activated Complement (C5b – C9)  Plasmin  Hypothermia  Interleukin-6
 Cathepsin G  Serotonin  Epinephrine

Question 4

Platelets Response to Activation

Answer 4

 Immediate shape change
express pseudo pods
express surface receptors GPIIb/IIIa GPIb
secrete receptor P selectin from granules

Question 5

GPIIb/IIIa receptors bind to

Answer 5

surface absorbed fibrinogen–use

fibrinogen as bridge to bind to other platelets

Question 6

P-selectin receptors bind to

Answer 6

monocytes & neutrophils to form aggregates

Question 7

Some platelets release a variety of chemicals and proteins called

Answer 7

thromboxane-A2, platelet factor 4, Beta-thromboglobulin, serotonin, etc.

Question 8

principal agonists of neutrophil activation

Answer 8

kallikrein and C5a

Question 9

other agonists involved in neutrophil activation

Answer 9

factor XIIa, heparin, MAC, interleukin 1 Beta, interleukin 8, TNF

Question 10

when neutrophils activated release contents of granules which are….. (9 of them)

Answer 10

ysosomal enzymes, elastase, myeloperoxidase, hydrogen peroxide, hydroxyl radicals, hypochlorous acid, hypobromous acid, acid hydrolases, collagenases

Question 11

types of receptors expressed when neutrophils are activated

Answer 11

Express MAC-1 (CD11b/CD18) & CD11c/CD18 receptors

Question 12

what do neutrophil receptors bind to

Answer 12

binds to fibrinogen, complement fragment, endothelial cells, collagen. binds with factor X and fibrinogen to facilitate thrombin formation

Question 13

neutrophil L selectin receptor

Answer 13

binds with P-selectin expressed by endothelial cells and platelets

Question 14

neutrophils contribute to what kind of injury

Answer 14

reperfusion injury

Question 15

Monocyte Activation

Answer 15

low activation during CPB by  C5a

 thrombin  bradykinin

Question 16

monocytes form conjugates with

Answer 16

platelets via GMP-140 and express

tissue factor

Question 17

monocyte activation effect on tissue factor

Answer 17

Delayed increase of tissue factor seen 20 hours post CPB

Question 18

monocyte activation releases what cytokines

Answer 18

IL-6 and IL-8 during and post CPB  IL-1, IL-2, IL-4 post CPB

Question 19

lymphocyte response to bypass

Answer 19

 Number of cells - reduced first week after bypass  Cell responsiveness to mitogens / other agonist –
reduced
Increases susceptibility of postoperative infections. Septic shock  Endocarditis

Question 20

activation agents for endothelial cells

Answer 20

 thrombin,C5a,variouscytokines,TNF

Question 21

endothelial cells produce

Answer 21

 prostacyclin,heparansulfate,thrombomodulin,protease
nexin-1, protein S, tissue factor pathway inhibitor, t-PA
 vasoactivesubstanceslikenitricoxide,endothelin,PAF, histamine, norepinephrine, bradykinin

Question 22

activated endothelial cells express what receptors

Answer 22

tissuefactor,P-selectin,E-selectin,ICAM-1,VCAM-1

Question 23

effect of activated endothelial cells

Answer 23

 Synthesize tissue factor to generate thrombin  Initiate fibrinolysis  Contribute to the overall acute inflammatory response
 Allow fluid and leukocytes to enter the interstitial space

Question 24

Possible Contributions to Bleeding After Cardiopulmonary Bypass Non-Platelet Related Causes

Answer 24

Hyper fibrinolysis
Heparin excess (inadequate neutralization, rebound)
Hypothermia
Protamine excess
Consumption of soluble coagulation factor(s)
Decreased von Willebrand’s factor

Question 25

Possible Contributions to Bleeding After Cardiopulmonary Bypass Platelet Related Causes

Answer 25

Thrombocytopenia Aspirin-induced platelet dysfunction Impaired aggregation response to agonists (epinephrine, collagen, ADP, thrombin Selective loss of youngest (most functional) platelets Platelet fragmentation / loss of membrane receptors Impaired platelet-mediated clot retraction Plasmin-induced platelet activation / dysfunction Platelet activation / dysfunction induced by C5b-9

Question 26

XII Hageman factor percentage of normal conc. needed for coag.

Answer 26

none

Question 27

XI Plasma thromboplastin antecedent percentage of normal conc. needed for coag.

Answer 27

20

Question 28

IX Christmas factor percentage of normal conc. needed for coag.

Answer 28

40

Question 29

VIII Antihemophilic factor percentage of normal conc. needed for coag.

Answer 29

30

Question 30

VII Proconvertin, serum prothrombin conversion percentage of normal conc. needed for coag.accelerato

Answer 30

25

Question 31

X Stuart factor percentage of normal conc. needed for coag.

Answer 31

40

Question 32

V Proaccelerin, labile factor percentage of normal conc. needed for coag.

Answer 32

40

Question 33

II Prothrombin percentage of normal conc. needed for coag.

Answer 33

40

Question 34

I Fibrinogen percentage of normal conc. needed for coag.

Answer 34

100 mg/dl

Question 35

Terumo coating

Answer 35

XCoating(poly(2-methoxyethylacrylate)(PMEA)-noheparin)

Question 36

Medtronic coating

Answer 36

 Carmeda(heparincoating–covalentbonded) |  Trillium(heparincoating–covalentbonded)  Balance® Biosurface (hydrophilic polymer coating-no heparin)

Question 37

Maquet coating

Answer 37

 Bioline(combinedalbuminandheparincoating)  Softline® (hydrophilic & hydrophobic polymer coating-no heparin)

Question 38

Sorin coating

Answer 38

P.h.i.s.i.o(syntheticphosphorylcholine-noheparin)

Question 39

Preop administration of corticosteroids attenuates

Answer 39

complement activation

Question 40

Aprotinin inhibits

Answer 40

plasmin directly high dose partially inhibits kallikrein – platelet sparing

Question 41

W-aminocarboxylic acids inhibit

Answer 41

inhibit cleavage of plasminogen to plasmin

Question 42

Platelet anesthesia

Answer 42

Reversible inhibition of platelets during procedure  Eptifibatide (Integrilin) with or without nitric oxide  Nitric oxide provides partial protection

Question 43

Complement inhibition drugs

Answer 43

 Pexelizumab  TP10