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Hematology and oncology ` hematology and oncology—PhySIology Hematology and oncology ` hematology and oncology—PhySIology SectIon III 411

Platelet plug formation (primary hemostasis)
4A 4B
INJURY EXPOSURE ADHESION ACTIVATION AGGREGATION
Endothelial damage vWF binds to exposed Platelets bind vWF via GpIb ADP binding to P2Y 12 Fibrinogen binds GpIIb/IIIa receptors and links platelets
→ transient collagen receptor at the site of injury receptor induces GpIIb/IIIa Balance between
vasoconstriction via vWF is from Weibel-Palade only (specific) platelets expression at platelet
neural stimulation reflex bodies of endothelial undergo conformational surface Pro-aggregation factors: Anti-aggregation factors:
and endothelin (released cells and α-granules of change TXA 2 (released PGI 2 and NO (released
from damaged cell) platelets by platelets) by endothelial cells)
↓ blood flow ↑ blood flow
Platelets release ADP and ↑ platelet aggregation ↓ platelet aggregation
Ca 2+ (necessary for
coagulation cascade), TXA 2
Temporary plug stops bleeding; unstable, easily dislodged
ADP helps platelets adhere
to endothelium Coagulation cascade
(secondary hemostasis)

Thrombogenesis Formation of insoluble fibrin mesh.
Aspirin irreversibly inhibits cyclooxygenase,
thereby inhibiting TXA synthesis.
2
Clopidogrel, prasugrel, and ticlopidine inhibit
ADP-induced expression of GpIIb/IIIa by
irreversibly blocking P2Y receptor.
12
Abciximab, eptifibatide, and tirofiban inhibit
GpIIb/IIIa directly.
Ristocetin activates vWF to bind GpIb. Failure
of aggregation with ristocetin assay occurs in
Clopidogrel, prasugrel,
ticlopidine Platelet von Willebrand disease and Bernard-Soulier
Inside vWF syndrome.
Aspirin platelets vWF carries/protects factor VIII; volksWagen
Fibrinogen
Factories make gr8 cars.
Fibrinogen COX
Arachidonic
ADP (P2Y 12 ) receptor TXA 2
acid
4B
4A
Deficiency: Glanzmann thrombasthenia
GpIIb/IIIa
Activated
Deficiency: Bernard- GpIIb/IIIa Abciximab, Thrombin- Protein C protein C
Soulier syndrome insertion eptifibatide, thrombomodulin Vascular endothelial cells
tirofiban complex
Deficiency: von
Willebrand Inside (vWF + factor VIII)
Subendothelial GpIb vWF disease endothelial Thromboplastin
collagen cells
tPA, PGI 2

FAS1_2019_10-HemaOncol.indd 411 11/7/19 5:04 PM