Plasma Coagulation System

Intrinsic Pathway

“contact system”

• all contact factors assemble on a negatively charged surface

• intrinsic Xase created

components of instrinsic Xase

• FIXa

• FVIIIa

• Ca2+

• phospholipids

extrinsic pathway 

“tissue factor pathway”

• seen with vascular injury 

• creates the extrinsic Xase

components of extrinsic xase

• FVIIa

• TF

• Ca2+

common pathway

where intrinsic and extrinsic converge

• when FX is activated into FXa

what does the intrinsic pathway contribute to?

• fibrinolysis 

• inflammation 

• complement activation 

• angiogenesis

• kinin formation 

what activates FX?

the intrinsic xase and extrinsic xase

which factors are zymogens/proteases?

• FII

• FVII

• FIX

• FX

• FXI

• FXII

• FXIII

• PK

which factors are considered cofactors?

• FIII

• FIV

• FV

• FVIII

• HK

which factors are regulators?

• FXVII

• FXIX

• FXX

• FXVI

which factors are fibrinolytic?

only plasminogen

what is the structure of fibrinogen?

large glycoprotein

• has three pairs of polypeptide chaines 

• dimeric

two D areas and one E area with alpha and beta polypeptides sticking from the E section

how is fibrinogen broken down into fibrin monomers?

1. proteolytic cleavage of bonds by thrombin (alpha and beta polypetides released)

2. spontaneous polymerization of fibrin monomers to form fibrin polymers 

3. fibrin polymers stabilized by FXIIIa cross-linking 

Where is vitamin K obtained?

through diet

• leafy greens

• fish

• liver

why is vitamin K necessary in the cogaulation cascade?

• gamma-carboxylation of glutamic acid residues to allow calcium to bind 

• reduced form required 

• recycled back into vitamin K by vitamin K epoxide reductase

what is the name of a medicine that affects vitamin k? how does it work?

warfarin or coumadin 

• it blocks vitamin K epoxide reductase which in turns makes other proteases not able to bind with calcium

what is the consequence of a vitamin k deficiency?

possible bleeding disorders (prothrombin, FVII, FIX, FX, PC, PS cannot become activated)

what role does calcium play in the pathway?

• cofactor in reactions

• binds to carboxyl groups of essential factors 

• component of all three complexes

how do platelets play a role?

• form physical primary plug

• reaction surface for intrinsic pathway 

• releases dialators and constrictors

how does thrombin play a role in procoagulation?

• cleaves fibrinogen 

• activates FV, FVIII, FXI and amplifies itself

• activates FXIII

• activates and recruits more platelets

• stimulates the release of VWF, PAI-1, TF

what anticoagulant roles does thrombin play?

• activates TAFI

• stimuates the release of SERPINS

• activates Protein C

How does Protein C regulate coag?

inhibits FVa and FVIIIa through cleaving active sites 

• thrombomodulin binds with thrombin and binds with free protein s 

how does tissue factor regulate coag?

inhibits the FVIIa/TF complex

• stops extrinsic pathway 

• protease inhibitor

• inhibits FXa’s active site in the presence of calcium

how does blood flow regulate coag?

returning to normal blood flow dilutes the concentration of activated factors and lets inhibitors bind and carry those complexes away

how does the liver play a regulatory role in coag?

removes activated factor/inhibitor complexes from circulation 

• LRP receptor on hepatocytes and liver macrophages

how do SERPINS regulate coag?

• creates a conformational change in both the inhibitor and serine protease 

• targets the serine active site

what are the three main SERPINS?

• antithrombin

• heparin cofactor II

• alpha 1 antitrypsin 

• alpha 2 macroglobulin 

antithrombin

most important SERPIN

• inactivates thrombin and other factors 

• enhanced by heparin 

which factors are made in the liver?

• FI

• FII

• FV

• FVII

• FVIII

• FIX

• FX

• FXI

• FXII

• FXIII

• HK

• PK