Blood Surface Interactions (Part 2)- Exam 3 Flashcards
What do erythrocytes do?
Uptake, transport, removal oxygen and carbon dioxide
What are 3 major types of blood cells?
RBCs, WBCs, platelets
What are two main types of leukocytes?
Granulocytes
Agranulocytes
What are 3 types of granulocytes?
Neutrophils
Eosinophils
Basophils
What percent are neutrophils? What do they do?
60-70%; destroy bacterial and phagocytosis
What percent are eosinophils? What do they do?
2-4%; destroy complex products antigen-antibody reactions
WHat percent are basophils? What do they do?
0.5-1%; release histamine and heparin; vasodilation
What are two types of agranulocytes?
Monocytes
Lymphocytes
What percent are monocytes? What do they do?
3-8%; transform into tissue macrophages
What percent are lymphocytes? What do they do?
20-25%; attach destroy/ deactivate bacteria, viruses, other foreign cells, acquired immune response
What are platelets (thrombocytes) involved in?
Coagulation
What are the 5 major cell types involved in blood surface interactions?
Platelets Neutrophils Monocytes Lymphocytes Endothelial Cells
Platelets- Initial/Early Activation
Surface contact with ECC
Heparin (increases sensitivity)
Circulating thrombin (agonist, probably initial activator)
Platelet-activating (PAF)
Platelets - Late Activation
Activated Complement (C5b - C9) Plasmin Hypothermia Interleukin-6 Cathepsin G Serotonin Epinephrine
Platelets respond to activation with immediate _____.
shape change
What shape changes do platelets in response to activation?
Express pseudo pods
Express surface receptors (GP2b/3a and GP1b)
Secrete receptors from granules (P-selectin)
5 actions of platelets responding to activation
1) Immediate shape change
2) GP2b/3a receptors bind to surface adsorbed fibrinogen (use fibrinogen as bridge to bind to other platelets)
3) P-selectin receptors bind to monocytes & neutrophils to form aggregates
4) Some platelets break off forming emboli
5) Some platelets release a variety of chemicals and proteins
Examples of the variety of chemicals and proteins that platelets release in response to activation
thromboxane-A2
platelet factor 4
beta-thromboglobulin
serotonin
_____ = very strong activation
neutrophils
Principal agonists of neutrophil
Kallikrein and C5a
Other neutrophil agonists are:
Factor 7a Heparin MAC Interleukin 1 Beta Interleukin 8 TNF
Events in neutrophil activation
- Release contents of granules
- Express MAC-1 (CD11b/CD18) & CD11c/CD18 receptors
- Express L-selectin receptor
Lysosomal enzymes, elastase, myeloperoxidase, hydrogen peroxide, hydroxyl radicals, hypochlorous acid, hypobromous acid, acid hydrolyses, and collagenases are contents released from _____ during neutrophils activation.
Granules
What does L-selectin receptor bing with?
P-selectin expressed by endothelial cells and platelets
What plays a major role in ischemia-reperfusion injury and responsible for much of inflammatory response associated with bypass?
Neutrophils
Monocyte activation is _____ during CPB.
slow
Monocyte activation is slow activation during CPB by (3):
C5a
Thrombin
Bradykinin
Monocytes are activated in ____ and ____.
wound and circuit
Monocytes form conjugates with platelets via ____ and express ____.
GMP-140
Tissue Factor
Delayed increase in tissue factor is seen ____ post CPB
20 hours
Monocyte activation produces and releases _____.
Cytokines
What cytokines are produced and released during and post CPB?
IL-6
IL-8
What cytokines are produced only after CPB?
IL-1
IL-2
IL-4
The number of lymphocyte cells are ____ first week after bypass?
reduced
Reduced lymphocyte response causes an _____ susceptibility of postoperative infections like septic shock and endocarditis.
increased
Endothelial cell activation agents are: (4)
Thrombin
C5a
Various Cytokines
TNF
____ cells produce prosstacyclin, heparan sulfate, thrombodulin, protease nexin-1, protein S, tissue factor and vasoactive substance like NO, endothelia, PAF, histamine, norepinephrine, and bradykinin.
Endothelial
What receptors do endothelial cells produce (5)?
Tissue Factor P-selectin E-selectin ICAM-1 VCAM-1
4 actions of activated endothelial cells:
1) Synthesize tissue factor to generate thrombin
2) Initiate fibrinolysis
3) Contribute to the overall acute inflammatory response
4) Allow fluid and leukocytes to enter the interstitial space
What 3 hematologist factors activated by CPB are soluble factors?
Coagulation cascade
Complement cascade
Fibrinolytic system
What 5 hematologist factors activated by CPB are cellular factors?
Platelets Neutrophils Monocytes Lymphocytes Endothelial cells
What active mediators are generated by the coagulation cascade?
Kallikrein
HMWK
Thrombin
What active mediators are generated by platelets?
TXA2
Serotonin
What active mediators are generated by neutrophils?
Oxygen radicals
Elastase
What active mediators are generated by monocytes?
Oxygen radicals
Cytokines
What active mediators are generated by lymphocytes?
Cytokines
What active mediators are generated by endothelial cells?
T-PA
Cytokines
What are the 6 non-platelet related causes of possible contributions to bleeding after CPB?
Hyper fibrinolysis
Heparin excess (inadequate neutralization, rebound)
Hypothermia
Protamine excess
Consumption of soluble coagulation factor(s)
Decreased vWF
What are the 8 platelet related causes of possible contributions to bleeding after CPB?
- Thrombocytopenia
- Aspirin-induced platelet dysfunction
- Impaired aggregation response to agonists (epi, collagen, ADP, thrombin)
- Selective loss of youngest (most functional) platelets
- Impaired platelet-mediated clot retraction
- Plasmin-induced platelet activation/dysfunction
- Platelet activation/dysfunction by C5b-9
What % of normal Factor 12 (Hageman factor) concentration is needed for coagulation?
None
What % of normal Factor 11 (Plasma thromboplastin antecedent) concentration is needed for coagulation?
20
What % of normal Factor 9 (Christmas factor) concentration is needed for coagulation?
40
What % of normal Factor 8 (Antihemophilic factor) concentration is needed for coagulation?
30
What % of normal Factor 7 (Proconvertin, serum prothrombin conversion accelerator) concentration is needed for coagulation?
25
What % of normal Factor 10 (Stuart factor) concentration is needed for coagulation?
40
What % of normal Factor 5 (Proaccelerin, labile factor) concentration is needed for coagulation?
40
What % of normal Factor 2 (Prothrombin) concentration is needed for coagulation?
40
How much of normal Factor 1 (Fibrinogen) concentration is needed for coagulation?
100 mg/dL
What are 3 ways to control blood-surface interface?
- Develop biomaterial that mimics the endothelial cell layer.
- Prevent or block activation of the blood during bypass.
- Prevent activated blood from reaching your circuit.
What active mediators are generated by the fibrinolytic system?
Plasmin
What active mediators are generated by the complement cascade?
C3a
C5-
C5b-9
What is a way to prevent activated blood from reaching your circuit?
Sequestered cardiotomy suction
What are 5 claims of using surface-bound circuit?
- Suppress thrombin formation
- Reduce blood loss and transfusion requirements
- Attenuate inflammatory response
- Depress platelet activation
- Decrease in clinical indicators of morbidity
What current systems have heparin coating?
Medtronic Carmeda
Medtronic Trillium
Maquet Bioline
How can we prevent or block activation of the blood during bypass?
Blood modification
4 processes of blood modification
- Preop administration of corticosteroids
- Antifibrinolytic agents
- Platelet anesthesia
- Complement inhibition
What is the purpose of administering corticosteroids preoperatively?
Attenuates complement activation
What does Aprotinin do?
Inhibits plasmin directly
What happens with high doses of Aprotinin?
Partially inhibits kallikrein–platelet sparing
What do W-aminocarboxylic acids do?
Inhibit cleavage of plasminogen to plasmin
3 types of platelet anesthesia
- Reversible inhibition of platelets during procedure
- Eptifibatide (Integrilin) with or without NO
- NO provides partial protection
2 types of complement inhibition
- Pexelizumab
- TP 10
