Blood Surface Interactions (Part 2)- Exam 3 Flashcards by Briana Lieberman

What do erythrocytes do?

Uptake, transport, removal oxygen and carbon dioxide

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What are 3 major types of blood cells?

RBCs, WBCs, platelets

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What are two main types of leukocytes?

Granulocytes

Agranulocytes

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What are 3 types of granulocytes?

Neutrophils
Eosinophils
Basophils

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What percent are neutrophils? What do they do?

60-70%; destroy bacterial and phagocytosis

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What percent are eosinophils? What do they do?

2-4%; destroy complex products antigen-antibody reactions

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WHat percent are basophils? What do they do?

0.5-1%; release histamine and heparin; vasodilation

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What are two types of agranulocytes?

Monocytes

Lymphocytes

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What percent are monocytes? What do they do?

3-8%; transform into tissue macrophages

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What percent are lymphocytes? What do they do?

20-25%; attach destroy/ deactivate bacteria, viruses, other foreign cells, acquired immune response

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What are platelets (thrombocytes) involved in?

Coagulation

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What are the 5 major cell types involved in blood surface interactions?

Platelets
Neutrophils
Monocytes
Lymphocytes
Endothelial Cells

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Platelets- Initial/Early Activation

Surface contact with ECC
Heparin (increases sensitivity)
Circulating thrombin (agonist, probably initial activator)
Platelet-activating (PAF)

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Platelets - Late Activation

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

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Platelets respond to activation with immediate _____.

shape change

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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)

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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

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Examples of the variety of chemicals and proteins that platelets release in response to activation

thromboxane-A2
platelet factor 4
beta-thromboglobulin
serotonin

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_____ = very strong activation

neutrophils

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Principal agonists of neutrophil

Kallikrein and C5a

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Other neutrophil agonists are:

Factor 7a
Heparin
MAC
Interleukin 1 Beta
Interleukin 8
TNF

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Events in neutrophil activation

Release contents of granules
Express MAC-1 (CD11b/CD18) & CD11c/CD18 receptors
Express L-selectin receptor

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Lysosomal enzymes, elastase, myeloperoxidase, hydrogen peroxide, hydroxyl radicals, hypochlorous acid, hypobromous acid, acid hydrolyses, and collagenases are contents released from _____ during neutrophils activation.

Granules

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What does L-selectin receptor bing with?

P-selectin expressed by endothelial cells and platelets

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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?

What % of normal Factor 9 (Christmas factor) concentration is needed for coagulation?

What % of normal Factor 8 (Antihemophilic factor) concentration is needed for coagulation?

What % of normal Factor 7 (Proconvertin, serum prothrombin conversion accelerator) concentration is needed for coagulation?

What % of normal Factor 10 (Stuart factor) concentration is needed for coagulation?

What % of normal Factor 5 (Proaccelerin, labile factor) concentration is needed for coagulation?

What % of normal Factor 2 (Prothrombin) concentration is needed for coagulation?

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