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

  • 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)

  • 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
  • alpha2antiplasmin 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