% of patients receiving Heparin that develop HIT
2-5% of patients receiving heparin
Causes bleeding
% of patients receiving Heparin that develop HITT
0.1-0.2% of patients receiving heparin
Causes thrombosis
HIT and HITT mechanisms ?
Heparin binds to PF4 (platelet factor 4) and induces formation of IgG antibodies
PF4-IgG complex activates platelets and does what to them ? With HIT and HITT?
Decreases circulating number of platelets
HIT defined as 40-50% decrease
HITT involves decrease AND any evidence of
thrombosis
plasma protein adsorption onto surface of ECC amount?
- very quick
* amount adsorbed depends on [protein] & intrinsic surface activity of biomaterial
plasma protein adsorption onto surface of ECC correlation?
correlation between physical / chemical
properties of biomaterial and activation of blood are made retrospectively–not possible to predict the response
plasma protein adsorption onto surface of ECC depends on what characteristics of the surface?
- wettability
- hydrophilic / hydrophobic ratio
- surface chemistry
- surface electrical properties
- roughness / porosity
- subsurface features
- distribution of functional receptor sites
contact activation of blood expose receptor sites on what? (3)
- blood cells
- plasma proteins (factor XII & complement protein 3)
- platelets
emboli formation can be caused by what? (5)
*surgery
*blood activation (fibrin emboli, macroaggregates of proteins and, lipoproteins, fat globules)
*homologous blood (if not filtered- fibrin, RBC debris, platelet and leukocyte aggregates)
*crystalloid solutions (debris/dust)
roller pumps (spallation)
Increased interstitial fluid formation caused by what?
increased capillary permeability
accumulation proportional to duration of bypass
Five protein systems in whole body coagulation?
Contact Activation System Intrinsic Coagulation Extrinsic Coagulation Fibrinolysis Complement Activation
Plasma Contact Activation: Four proteins involved?
factor XII
prekallikrein
high-molecular-weight kininogen (HMWK)
factor XI
For factor XII to be absorbed onto foreign surface of ECC - what two things must be present?
prekallikrein & HMWK must be present
Once factor XII changes shape it produces what?
active protease factor XIIa and XIIf
Factor XIIa cleaves prekallikrein into what?
to kallikrein (strong neutrophil agonist)
Factor XIIa Activates factor XI to XIa: what must be present? and what does XIa activate ?
kallikrein & HMWK must be present
factor XIa activates intrinsic coagulation cascade–thrombin production
Factor XIIa cleaves HMWK into what?
to bradykinin ( potent vasodilator )
Factor XIIa is an agonist of what?
factor XIIa weak neutrophil agonist
Intrinsic Coagulation Cascade initiated by what?
Initiated by plasma contact activation
Initiated directly by blood contact with the ECC
Extrinsic Coagulation Cascade initiated by what?
Initiated by the expression of tissue factor on
nonvascular cells
What are the two forms of tissue factor that are expressed when extrinsic coagulation cascade is initiated?
cell bound tissue factor
soluble plasma tissue factor
Binds to and activates factor VII activates what factor?
factor X
Thrombin Actions (4)
Production of fibrin from fibrinogen
Cross-linking fibrin
Activating platelets
Stimulating the production of tissue plasminogen activator (tPA) by endothelial cells
Compliment system made up of how many proteins ?
30+ proteins–most inactive enzyme precursors
Complement Pathway entails 3 paths?
Common Pathway
Alternative Pathway
Terminal Pathway
Alternative Pathway initiated by what two things?
Initiated by C3b (a product of the classical pathway)
Initiated by spontaneous activation on a continuous basis
Feedback loop for amplification
Terminal Pathway does what?
Classical and Alternative merge at the level of C3 convertase production
Classical Pathway initiated by what?
Initiated by antigen-antibody complexes
End Product-Membrane Attack Complex
Works to prevent / limit damage from invading organism or toxin by what? (7)
opsonization lysis agglutination neutralization of viruses chemotaxis activation of mast cells and basophils inflammation
End Product-Membrane Attack Complex OPSONIZATION does what?
neutrophils & macrophages activated
they engulf bacteria to which antigen-antibody complex is attached
End Product-Membrane Attack Complex
LYSIS final product?
final product called lytic complex or
terminal complement complex
•creates a pore in the cell membrane of bacteria or other invading organisms that
allows the influx of ions and water into the
cell
End Product-Membrane Attack Complex
AGGLUTINATION does what?
complement products change surface of invading organisms
•organisms adhere to each other
End Product-Membrane Attack Complex
neutralization of viruses how?
products can attack structures of some
viruses and render them non-virulent
C5a causes what of neutrophils
and macrophages?
chemotaxis
large number phagocytes migrate to area
mast cells and basophils are activated by what?
activated by C3a, C4a, & C5a
mast cells and basophils release what?
cells release histamine and other substances
into local fluids
mast cells and basophils results in what?
results increased local blood flow &
increased leakage of fluid and protein into
the tissue
inflammation does what to vasomotor tone, cap permeability and cardiac function ?
increased capillary permeability
altered vasomotor tone
impaired cardiac function
