Vitamin K Pathway in Coagulation Cascade
- oxidized vitamin K is reduced by epoxide reductase
- Reduced vitamin K activates factors (2, 7, 9, 10, C, S)
Warfarin inhibits epoxide reductase
Neonates lack enteric bacteria (makes vitamin K)
Protein C pathway
- protein C activated by thrombomodulin (endothelial cells)
- Activated Protein C (with Protein S) cleaves and inactivates Va and VIIIa
Factor V Leiden: mutated factor V resistant to cleavage by protein C
Plasminogen pathway
- Plasminogen converted to plasmin by tPA
2) plasmin cleaves fibrin to become breakdown products
tPA clinically used as thrombolytic
Antithrombin
Inhibits factors 2, 7, 9, 10, 11, 12
Activated by heparin
Steps for Platelet Plug Formation
Step 1: Transient vasoconstriction of damaged vessels
- reflex neural stimulation, endothelin release from endothelial cells
Step 2: Platelet adhesion
- vWF (from Weibel-Palade bodies of endothelial cells and alpha granules of platelets) binds to exposed subendothelial collagen
- platelet bind to vWF by GP1b receptor
Step 3: Platelet degranulation
- adhesion induces shape change and degranulation (ADP, Ca2+, TXA2, serotonin)
- ADP released and binding to receptors promote exposure of GPIIb/IIIa receptors on platelets
- TXA2 synthesized by platelet COX released to promote platelet aggregation
- serotonin increases vasodilation and vascular permeability
Step 4: Platelet aggregation
- fibrinogen binds GPIIb/IIIa receptors as linking molecule resulting in platelet plug
Pro and Anti aggregation factors for platelets
Pro:
TXA2, decreased blood flow, increased platelet aggregation
Anti:
PGI2 (Prostacyclin), increased blood flow, decreased platelet aggregation
Erythrocyte sedimentation rate
Acute-phase reactants in plasma (e.g. fibrinogen) can cause RBC aggregation, increasing sedimentation rate (RBC aggregates have higher density than plasma)
Increased ESR rate: infections, autoimmune (SLE, RA, temporal arteritis), malignant neoplasms, GI disease (UC), pregnancy
Decreased ESR rate: polycythemia, sickle cell anemia, congestive heart failure, microcytosis, hypofibrinogenemia
