HEMOSTASIS: 4 Phases

Phase 1: Vascular Spasm/Vasoconstriction – Trauma to the vessel wall results in a transient smooth
muscle contraction that causes a decrease in blood flow to the area

 Caused by: local myogenic spasm, factors released from the injured vessel wall (endothelin,
Ca2+), and nervous reflexes

Phase 2: Primary Hemostasis or the formation of a Platelet Plug

 Exposure of subendothelial collagen

 Platelet adhesion from Gp-IA and Gp-IB to subendothelial collagen
o Gp-IA binds directly
o Gp-IB bind via von Willebrand Factor (vWF)
 Platelet activation causing a shape change and degranulation with release of ADP
 ADP binds to neighbor platelets causing an increase in intracellular Ca2+, a decrease in
intracellular cAMP, and activation of Phospholipase A
o Leading to an increase in Thromboxane (TXA2)
 Additional platelets recruited to site of injury
 Platelet aggregation via fibrinogen linking adjacent platelets (platelet plug)
o Linked via GpIIB/IIIA

Phase 3: Secondary Hemostasis or Coagulation – Conversion of blood from liquid state to a solid, gel like
state (extrinsic, intrinsic, and common pathways)

 Extrinsic Pathway (activated via tissue injury)

o Tissue Injury  Release of Tissue Factor (Factor III)  Activated form is Factor IIIa
o Factor IIIa activates Factor VII  activated form is Factor VIIa
o Factor IIIa + Factor VIIa + Ca2+ + platelet phospholipids activate Factor X
o Factor Xa (activated form)
 Intrinsic Pathway (activated via pathology or stimulus)
o Exposure of collagen  activation of Factor XII  activated form is Factor XIIa
o Factor XIIa is sometimes called Hageman Factor
o XIIa activates Factor XI  XIa
o XIa activates Factor IX  IXa
o Thrombin activates Factor VIII  VIIIa
o Factor VIIIa + Factor IXa + Ca2+ + platelet phospholipids activate Factor X
o Factor Xa (activated form)
 Common Pathway (utilizes activated Factor X)
o Thrombin activates Factor V  Va
o Factor Va + Factor Xa + Ca2+ + tissue phospholipids form Prothrombin Complex
o Prothrombinase complex splits prothrombin to form thrombin (MOST IMPORTANT
STEP)
o Thrombin acts on Fibrinogen to form Fibrin
o Fibrin monomers link together via Hydrogen bonds to form a soft clot
o Thrombin activates Factor XIII  XIIIa
 o XIIIa covalently cross-links the connected Fibrin monomers to form a hard clot

Phase 4: Tertiary Hemostasis or Fibrinolysis – The degradation of cross-linked Fibrin to form D-dimers

 Tissue Plasminogen Activator (intrinsic) activates Plasminogen to form Plasmin

o Urokinase and Streptokinase are exogenous activators of Plasminogen
 Plasmin degrades Fibrin to D-dimers

Pathway Factors:

 Factor I – Fibrinogen (common)

 Factor II - Prothrombin (common)
 Factor III -Tissue Factor (extrinsic)
 Factor IV - Calcium (common)
 Factor V (common)
 Factor VII (extrinsic)
 Factor VIII (intrinsic)
 Factor IX (intrinsic)
 Factor X (common)
 Factor XI (intrinsic)
 Factor XII (intrinsic)
 Factor XIII (common)

Drugs: Anti-Coagulants

 Aspirin – irreversible inhibitor of COX-1 and COX-2 that decreases TXA2 release from platelets to
decrease clotting ability
 Heparin – activates Antithrombin-III which inactivates Thrombin and all its actions
 Warfarin – inhibits VKOR which prevents the regeneration of the active form of Vitamin K
leading to a decrease in matured clotting factors II, VII, IX, and X and in turn a decreased ability
of blood to clot
 Streptokinase – activates Plasminogen to form Plasmin which leads to a breakdown in blood
clots