01 Coagulation

Bleeding

• 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

• hemophilia: low 8 or 9

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

• needed in both pathways

• 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)

img

• 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

• break up thrombus

• 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