Remember, we are exposing subendothelium, collagen, and fibronectin

1. Von Willibrand Factor (VWF) binds to subendothelial proteins
2. platelet binds to VWF via its GpIb receptor
3. leads to platelet changing confirmation (by shrinking up of actin and myosin) and releasing the contents in their granules
   • ADP
   • serotonin
   • catecholamines
   • fibrinogen
   • platelt derived growth factor

1. ADP amplifies the aggregation
2. exposure of membrane receptors (GpIIb and GpIIIa) bound by fibrinogen
   1. crosslinks the platelets

2 alpha chains

2 beta chains

2 gamma chains

• most exist in inactive form
• many are Ser proteases

II

VII

IX

X

in ER membrane:

1. Glu residue converted to gamma carboxy Glu via oxidation of Vitamin K to become Vit K epoxide

1. thromboplastin (factor III aka tissue factor[TF]) is located on membrane of cells in endothelium
2. Factor VII binds to TF, activating Factor VII
3. factor X and IX bind to the active factor VII, leading to a proteolytic cleavage by factor VII that will activate factors X and IX

1. high molecular weight kinnogen (HMW-kinnogen) binds to collagen
2. pre-kallikren binds to HMW-kinnogen
3. Factor XII binds to HMW kinnogen and collagen, and will activate prekallikrein to kalliikrein
4. kallikrein will in turn activate factor XII to XIIa
5. Factor XIIa will activate factor XI to XIa
6. Factor XIa activates factor IX to IXa

• during pathways, it will bind to phospholipids on membrane of subendothelium
• in our Ser proteases, like factor IXa, it will bind to our carboxyl groups in our gamma carboxy glutamate

1. factor IXa, while on platelet membrane (bound to phospholipids with calcium), will activate factor X to factor Xa
2. factor Xa activates factor V to factor Va
3. factor Xa activates factor II to IIa
4. factor IIa will activate factor V to Va
   1. when Va joins Xa, the complex moves significantly faster in activating factor II to IIa
5. factor IIa will activate factor XIII to XIIIa
6. factor IIa will activate factor I to Ia (WE NOW HAVE FIBRIN)

1. thrombin hydrolyzes a peptide bond in the alpha chain and the beta chain which liberates a small peptide, now its fibrin
2. allows the fibrin molecules to polymerize, forming a solft clot
3. factor XIIIa forms a hard clot by forming crosslinks between fibrin molecules

• transglutaminase
• form peptide bond between glutaminyl group in one peptide chain and a lysyl group in another peptide chain

• antithrombin
• protein C/protein S
• TFPI (tissue factor pathway inhibitor)
• plasminogen

1. binds and forms a complex with heparin
2. this complex will bind to the Ser proteases
   1. factors II, IX, X, XI
3. when the proteases bind, they are inactivated

1. thrombomodulin found in damaged cell surfaces
2. factor IIa thrombin binds and this leads to a change in activity
3. thrombin will initiate activity that will produce protein C
4. protein C will form a complex with protein S
5. this complex of protein C and S will take factors Va and VIIIa and inactivate them

1. lipoprotein (contains apoA) in circulation and when I make too much factor Xa, it will bind Xa and form a complex
2. we also have a complex with a tissue factor and factor VIIa
3. the lipoprotein-Xa complex will bind to the TF-VIIa complex
4. leads to inactivation of factor VIIa to VII and Xa to X

1. plasminogen binds to damaged endothelium
2. damaged endothelium produced tissue plasminogen activator
3. tissue plasminogen activator binds to plasminogen, activates it to plasmin
4. plasmin will break fibrin into fragments

Remember, at the same time, endothelium releases tissue plasminogen activating inhibitor to inhibit tissue plasminogen.

• used as anticoagulant (also rat poison)
  • it looks like vitamin K, and it will block creation of gamma carboxy glutamate in active site of Ser proteases