Coagulation

Question 1

What 4 things happen when a vessel is injured?

Answer 1

• Vasoconstriction
• Tissue Factor release from endo –> FVII (extrinsic path)
• Exposed endo becomes surface for FXII and FXI to
  contact (intrinsic path)
• Collagen is exposed - platelet aggregation (GPIaIIa - collagen)

Question 2

Secondary Hemostasis

Answer 2

• (end goal = fibrinogen –> fibrin)
• Cascade of zymogen activation –> fibrin then activation of FXIII stabilizes clot
• Retraction of clot by interacting w/ thrombosthenin of platelets
• Intrinsic Path (now thought to initiate)
  - FXII contact endo surface to become activated
  - FXII activated FXI which activates FIX
  - Then IXa, VIII, PF-3 and Ca++ all activate FX
• Extrinsic Path (now thought to sustain)
  - Tissue factor (from endo) –> activates FXII
  - VIIa, PF-3 and Ca++ activate FX
• Common Path
  - Xa, PF-3 and Ca++ activate FV
  - FVa activates FII (prothrombin) –> FIIa (thrombin) which turns fibrinogen to fibrin (FIa) and activates FXIII to stabilize clot

Question 3

6 Roles of Thrombin

Answer 3

• Fibrinogen –> fibrin
• XIII –> XIIIa (clot stabilization)
• V–> Va
• VIII –> VIIIa (off VWF carrier)
• Protein C –> activated protein C (protective measure -
  clot inhibitor)
• Platelet aggregation

Question 4

5 Clot Inhibitors

Answer 4

• Antithrombin (or alpha-2-globulin) which neutralizes thrombin mainly
• Protein C (Vit K and protein S dep) - when act it inactivates FVa and FVIIIa
  
  • Absence = purpura fulminans in infants
  • Protein S is also Vit K dep and is co-factor for Protein C
• TFPI (tissue factor pathway inhibitor) - inhibits TF-FXII complex
• Alpha -2 macroglobulin - inhibits Xa and thrombin
• Alpha-1-antotrypsin -inhibits Xa

Question 5

Fibrinolysis

Answer 5

• Plasminogen –> plasmin which cleaves fibrin/fibrinogen –> FDP/FSP or cleave fibrin alone –> D-dimers
• Fibrinolysis is activated by XIIa and others in plasma AND by extrinsic t-PA (made by endo cells or given synthetically)

Question 6

What 3 things regulate fibrinolysis?

Answer 6

• PAI (plasminogen activator inhibitor) blocks t-PA
• Antiplasmin and alpha-2-macroglobulin both inhibit plasmin once it is formed
• TAFI - inhibits plasminogen directly

Question 7

Primary v Secondary Hemostasis Problems

Answer 7

Primary Hemostasis Problem

• Mucosal bleeding (oropharynx, GI, GU)
• Early b/c no platelet plug formed
• Platelet or VWF problem
• More mild bleeding

Secondary Hemostasis Problems

• Joint, muscle, body cavity bleeding
• Late b/c plug is formed but only temporary
• Hemophilia, factor def, Vit K def, liver disease, DIC
• More severe bleeding

Question 8

APTT v PT

Answer 8

• APTT - tests intrinsic by starting w/ FXII and collagen
• PT (prothrombin time) - tests extrinsic by starting w/ TF and FVII
• If PT and APTT are normal then check platelets next (closure time)

Question 9

TT v RT

Answer 9

• TT (thrombin time) - give extra thrombin to pt plasma so only dependent on fibrinogen
• RT - reptilase which breaks fibrinogen –> fibrin regardless of thrombin
• If TT prolonged but RT normal then on heparin (anti-thrombin cancels out extra thrombin)
• If both TT and RT prolonged then problem w/ fibrinogen itself