Arterial vs Venous clotting response
arterial- 1) platelets 2) forming fibrinogen
venous 1) thrombin generation
the 2 clotting factor types
proenzyme (become enzyme when activated- also called zymogens)
procofactors (become cofactors- help something else become activated)
Platelet Aggregation
- accelerates local process
- receptor site for factors
- releases factors
- provides negative charge surface
Coagulation Cascade
series of proteolytic reactions that lead to fibrin clot
Coagulation Cascade 3 Pathways
1) intrinsic- blood reacts with stuff (collagen, membrane)
- activated partial thromboplastin time (aPTT)
2) extrinsic- release of tissue factor and reacts with blood
- prothrombin time (PT)
3) common pathway- production of thrombin and fibrin
- PT
Coagulation Cascade Pros and Cons
pros- understand Ca dependent, can do in lab
con- wrong about intrinsic/extrinsic independence, no fluid moving/no interactions
Cell Based Model
thrombin generation
1) Initiation- on TF bearing cell
2) Amplification- platelets/cofactors active
3) Propagation- make lots of thrombin (thrombin burst) to make fibrin clot
4) Clot formation
Platelet Adhesion
vWf held in place by subednothelial collagen
GPIb binds to vWf, but not very strong
this causes transmembrane signaling
Platelet Activation
- GPIIb/IIIa + vWf= secure platelet on subendo
- GPIa/IIa binds to collagen on subendo
- GPIV also binds to collagen
Platelet Activation Goals
- recuite
- vasoconstrict
- matrix
- acceleration of fibrin
- protect form fibrinolysis
Recruitment of Additional Platelets
- these come from within platelets
1) thromboxane A2 (TXA2)- platelet agonist and constrictor (cyclooxyrgenase cleaves arachidonic)
2) serotonin- agonist/constrictor
3) ADP- agonist
Platelet Plug
GPIIb/IIIa + Ca binds to fibrinogen (or vWf)- forms bonds between multiple platelets
4 Anticoagulants that helps with Termination (preventers spreading of clot)
TF, Protein C, Protein S and Antithrombin II
TFPI
tissue factor pathway inhibitor
- forms a 4 part complex= TF, VIIa, Xa, TFPI= inactivates extrinsic tenase complex (“priming thrombin”)
Protein C and S
inactivate Va and VIIIa
- vitamin K dependent
- activated by thrombin and Protein S
ATIII
antithrombin III
- inhibits thrombin (IXa, Xa, XIa, XIIa)
- HEPARIN helps ATIII to prevent clotting
Things that convert plasminogen to plasmin
- uPA (drug), tPA (tissue-type plasminogen activator), XIa, XIIa, Kallikrein
Endogenous Anticoagulants
endothelial releases NO (dilate) and prostacyclin/PGI2 (inhibits platelet aggregation) and ADPase (inactivates platelets)
5 things that cause bleeding
1) mechanical (proline insufficiency- surgeon mess up)
2) insufficient fibrin formation
3) insufficient clot integrity
4) insufficient clot adhesion
5) fibrinolysis
