Primary Hemostasis: Platelet Plug Formation

• Hemostasis prevents blood loss when a blood vessel is injured.
• It has two types: primary and secondary.

Primary Hemostasis

• Platelets clump together to form a plug around the injury site.
• Involves 5 steps: endothelial injury, exposure, adhesion, activation, and aggregation.

Endothelial Injury

• Nerves attached to endothelial and smooth muscle cells trigger vascular spasm, narrowing the vessel and reducing blood flow.
• Nitric oxide and prostaglandin secretion decreases, while endothelial cells secrete endothelin, causing smooth muscles to contract.

Exposure

• Collagen beneath the endothelial cells gets exposed.
• Damaged endothelial cells release von Willebrand factor, which binds to the exposed collagen.

Adhesion

• Circulating platelets encounter von Willebrand factor bound to collagen.
• Platelets bind to von Willebrand factor via the surface protein GP1B.

Activation

• Platelets binding to von Willebrand factor via GP1B become "activated."
• Platelets change shape, forming tentacle-like arms.
• Platelets release:
  • von Willebrand factor
  • Serotonin (attracts more platelets)
  • Calcium (useful in secondary hemostasis)
  • Adenosine diphosphate (ADP): activates other platelets and causes expression of GPIIB/IIIA
  • Thromboxane A2: activates other platelets and causes expression of GPIIB/IIIA
• Platelet activation creates a positive feedback loop.
• Undamaged endothelial cells secrete prostaglandin and nitric oxide to inhibit platelet activation.
• Prostaglandin and nitric oxide act as platelet inhibitors, while ADP and thromboxane A2 act as platelet activators.

Aggregation

• GPIIB/IIIA binds to fibrinogen.
• Platelets attach to other platelets via fibrinogen bridges, rapidly aggregating at the injury site to form a plug.

Secondary Hemostasis

• Clotting factors (enzymes) are activated, leading to the activation of fibrin (Factor Ia).
• A fibrin mesh forms around the platelet plug to reinforce it.
• Two pathways: extrinsic and intrinsic, both culminating in the activation of Factor X and proceeding to create a common pathway.

Extrinsic Pathway

• Activated by tissue factor (Factor III) found outside the blood.
• Trauma exposes tissue factor in cell membranes.
• VIIa binds to tissue factor and calcium, forming the VIIa-TF complex.
• VIIa-TF complex cleaves Factor X into Xa.

Intrinsic Pathway

• All factors are found within the blood.
• Factor XII contacts negatively charged phosphates or subendothelial collagen, activating into XIIa.
• Factor XIIa activates Factor XI into XIa, which combines with calcium to activate Factor IX into IXa.
• Factor IXa forms a complex with calcium and Factor VIIIa, activating Factor X (to Xa).

Common Pathway

• Factor Xa activates Factor V into Va.
• The prothrombinase complex (Factor Xa + Factor Va + Ca2+) activates prothrombin/Factor II to thrombin/Factor IIa.
• Each prothrombinase complex can activate thousands of thrombin molecules.
• Thrombin activates fibrinogen to fibrin, forming the fibrin clot.
• Thrombin binds to platelet receptors, causing activation.
• Activates cofactors Factor V, Factor VIII, and Fibrin. Which activates fibrinogen to Fibrin
• Thrombin activates Factor XIII, and Factor XIIIa forms cross-links between fibrin chains, reinforcing the fibrin mesh.

Primary hemostasis involves platelets clumping together to form a plug around an injury site in five steps: endothelial injury, exposure of collagen, adhesion of platelets to von Willebrand factor, platelet activation, and aggregation. This process is crucial for preventing blood loss from damaged blood vessels.