01 Coagulation
- occurs before any thrombus formation
- coagulation = fibrin formation into clot to stop blood loss
Coagulation Factors
- First soluble. Become insoluble when activated
Coagulation Cascade
Main
- fibrin insoluble, precipitate
Tissue Factor
- when endothelium intact, no contact
- when damaged, tissue factors expressed
- not very effective, no amplification
Thrombin
- thrombin amplification
- 5, 8, 11 activate more 10
Von Willebrand
- unique: in endothelium
- megakaryocytes: von willebrand stored in platelets and endothelium
- injury: factor 8 released from vWF, thrombin formation
Factor 13
- formed but not crosslinked
Factor 12
- activate coagulation system when exposed to silica
Extrinsic and Intrinsic
- how written in textbook
- 1st pathway: TF pathway from TF:VIIa
- 2nd pathway: factor 12
- T: which factors activated by thrombin
- phospholipid: required, exists on TF cells or platelets
Calcium
- used to be called factor 4
Kinin
- contact pathway: activated when plasma in contact with negatively charged substances
- link between coagulation and inflammation
- generated by factor 12
- factor 12 leads to synthesis of bradykinin
- link between coagulation system and kinin system (inflammation)
- cannot activate bradykinin
- routine test of PTT shows prolonged. No medical problems because 12 doesn't have a lot of physiologic significance
Coagulation Inhibitors
Antithrombin III
- activated by healthy endothelial cells
Protein C and S
- healthy endothelium: produce lots of thrombomodulin, less thrombin
- deficiency in one or both: hypercoagulable
- factor 5 leiden mutation: cannot be inactivated by protein C/S: hypercoagulable
- just know plasma level increased with heparin
- Tissue factor pathway inhibitor (or TFPI) is a single-chain polypeptide which can reversibly inhibit Factor Xa (Xa). While Xa is inhibited, the Xa-TFPI complex can subsequently also inhibit the FVIIa-tissue factor complex. TFPI contributes significantly to the inhibition of Xa in vivo, despite being present at concentrations of only 2.5 nM.
Plaminogen
- break down fibrin
- converted to active in plasma
- contain crosslinked bond by 13
- indicates crosslinked fibrin clot broken down
- FDP can increase without clot formation: not useful
- break down of fibrinogen but not clot
- break down other clotting factors: deplete clotting factors
- looks like DIC
- increased in prostate cancer and cirrhosis
- alpha2- antiplasmin inhibitor of plasmin. Loss can leads to overactivation
Vitamin K
ESR
- inflammation: increased protein levels
- proteins are sticky, clump RBCs together, settle faster to bottom faster
- liver makes more fibrinogen that will increase ESR
Backlinks