Blood surface interactions part 2 Flashcards
Identify the 5 key blood cell types involved in the response to ECC
Platelets Neutrophils Monocytes Lymphocytes Endothelial Cells
what causes Platelet Initial / Early Activation (4 things)
Surface contact with ECC
Heparin increases sensitivity
Circulating thrombin is a powerful agonist and probably initial activator
Platelet-activating factor (PAF)
what causes Platelets Late Activation (7 things)
Activated Complement (C5b – C9) Plasmin Hypothermia Interleukin-6
Cathepsin G Serotonin Epinephrine
Platelets Response to Activation
Immediate shape change
express pseudo pods
express surface receptors GPIIb/IIIa GPIb
secrete receptor P selectin from granules
GPIIb/IIIa receptors bind to
surface absorbed fibrinogen–use
fibrinogen as bridge to bind to other platelets
P-selectin receptors bind to
monocytes & neutrophils to form aggregates
Some platelets release a variety of chemicals and proteins called
thromboxane-A2, platelet factor 4, Beta-thromboglobulin, serotonin, etc.
principal agonists of neutrophil activation
kallikrein and C5a
other agonists involved in neutrophil activation
factor XIIa, heparin, MAC, interleukin 1 Beta, interleukin 8, TNF
when neutrophils activated release contents of granules which are….. (9 of them)
ysosomal enzymes, elastase, myeloperoxidase, hydrogen peroxide, hydroxyl radicals, hypochlorous acid, hypobromous acid, acid hydrolases, collagenases
types of receptors expressed when neutrophils are activated
Express MAC-1 (CD11b/CD18) & CD11c/CD18 receptors
what do neutrophil receptors bind to
binds to fibrinogen, complement fragment, endothelial cells, collagen. binds with factor X and fibrinogen to facilitate thrombin formation
neutrophil L selectin receptor
binds with P-selectin expressed by endothelial cells and platelets
neutrophils contribute to what kind of injury
reperfusion injury
Monocyte Activation
low activation during CPB by C5a
thrombin bradykinin
monocytes form conjugates with
platelets via GMP-140 and express
tissue factor
monocyte activation effect on tissue factor
Delayed increase of tissue factor seen 20 hours post CPB
monocyte activation releases what cytokines
IL-6 and IL-8 during and post CPB IL-1, IL-2, IL-4 post CPB
lymphocyte response to bypass
Number of cells - reduced first week after bypass Cell responsiveness to mitogens / other agonist –
reduced
Increases susceptibility of postoperative infections. Septic shock Endocarditis
activation agents for endothelial cells
thrombin,C5a,variouscytokines,TNF
endothelial cells produce
prostacyclin,heparansulfate,thrombomodulin,protease
nexin-1, protein S, tissue factor pathway inhibitor, t-PA
vasoactivesubstanceslikenitricoxide,endothelin,PAF, histamine, norepinephrine, bradykinin
activated endothelial cells express what receptors
tissuefactor,P-selectin,E-selectin,ICAM-1,VCAM-1
effect of activated endothelial cells
Synthesize tissue factor to generate thrombin Initiate fibrinolysis Contribute to the overall acute inflammatory response
Allow fluid and leukocytes to enter the interstitial space
Possible Contributions to Bleeding After Cardiopulmonary Bypass Non-Platelet Related Causes
Hyper fibrinolysis
Heparin excess (inadequate neutralization, rebound)
Hypothermia
Protamine excess
Consumption of soluble coagulation factor(s)
Decreased von Willebrand’s factor
Possible Contributions to Bleeding After Cardiopulmonary Bypass Platelet Related Causes
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
XII Hageman factor percentage of normal conc. needed for coag.
none
XI Plasma thromboplastin antecedent percentage of normal conc. needed for coag.
20
IX Christmas factor percentage of normal conc. needed for coag.
40
VIII Antihemophilic factor percentage of normal conc. needed for coag.
30
VII Proconvertin, serum prothrombin conversion percentage of normal conc. needed for coag.accelerato
25
X Stuart factor percentage of normal conc. needed for coag.
40
V Proaccelerin, labile factor percentage of normal conc. needed for coag.
40
II Prothrombin percentage of normal conc. needed for coag.
40
I Fibrinogen percentage of normal conc. needed for coag.
100 mg/dl
Terumo coating
XCoating(poly(2-methoxyethylacrylate)(PMEA)-noheparin)
Medtronic coating
Carmeda(heparincoating–covalentbonded)
Trillium(heparincoating–covalentbonded) Balance® Biosurface (hydrophilic polymer coating-no heparin)
Maquet coating
Bioline(combinedalbuminandheparincoating) Softline® (hydrophilic & hydrophobic polymer coating-no heparin)
Sorin coating
P.h.i.s.i.o(syntheticphosphorylcholine-noheparin)
Preop administration of corticosteroids attenuates
complement activation
Aprotinin inhibits
plasmin directly high dose partially inhibits kallikrein – platelet sparing
W-aminocarboxylic acids inhibit
inhibit cleavage of plasminogen to plasmin
Platelet anesthesia
Reversible inhibition of platelets during procedure Eptifibatide (Integrilin) with or without nitric oxide Nitric oxide provides partial protection
Complement inhibition drugs
Pexelizumab TP10
