The term hemostasis means prevention of blood loss. Normal hemostasis is a consequence of tightly regulated processes that maintain blood in constant movement inside vessels. When a vessel is severed, several cells, factors and cofactors are activated to prevent the continued loss of blood and to repair the damage. Hemostasis is divided into primary and secondary hemostasis. Primary hemostasis is characterized by the formation of a platelet plug and is necessary to quickly stop the vascular content from leaking outside of the vessel. Secondary hemostasis stabilizes the platelet plug with fibrin polymers forming a solid mass tightly adhered to the vessel at the site of the injury.
Step 1: Vasoconstiction
Prostacyclin and Nitric Oxide are produced in the endothelial cells of blood vessels to keep them dilated and allow blood to easily flow through. Immediately after a blood vessel has been injured, these vasodilators are inhibited and the smooth muscle inside the vessel wall contracts. This reduces the the flow of blood from the ruptured vessel and therefore prevents leakage. The initial vasoconstriction is caused by neurogenic vasoconstriction, the release of endothelin by damaged endothelial cells and Thromboxane A2 from the platelets, and local myogenic spasm. The more severly a vessel is damaged, the greater degree of vascular spasm, lasting for many minutes or even hours.
Step 2: Platelet Adhesion
Platelets, also called thrombocytes, play an important role in primary hemostasis. They have a flat disc shape, normally 1-4 micrometers in diameter, and contain α and delta granules. They are formed by megakaryocytes in the bone marrow, do not have nuclei and cannot reproduce. Their cytoplasm contains actin and myosin molecules , similar to those found in muscle cells, and thrombosthenin allowing platelets to contract.
Von Willebrand Factor (vWF) is released from platelets and from the Weibel Palade bodies of damaged endothelial cells. The secreted vWF binds with subendothelial collagen at the site of injury and its also an attractant to thrombocytes. Receptor GP1b, located on the cell wall of these thromobocytes, attaches to von Willebrand Factor and activates the platelet.
Step 3: Platelet Degranulation
When activated, platelets immediately undergo change. They begin to swell, they assume irregular forms with numerous pseudopods protruding from their surfaces. They release Alpha and Delta granules. Alpha granules contain: insulin-like growth factor 1, platelet-derived growth factors, TGFβ, platelet factor 4 (which is a heparin-binding chemokine) and other clotting proteins (such as thrombospondin, fibronectin, factor V, and von Willebrand factor). Delta granules contain: adenosine diphosphate (ADP), adenosine triphosphate (ATP), calcium (necessary for several steps of the coagulation cascade in Secondary Hemostasis), histamine and serotonin. The released vWF also attaches to exposed subendothelial collagen and allows more platelets to bind to them.
Step 4: Platelet Aggregation
TxA2, derived from the cyclooxigenase pathway, promotes platelet aggregation and vasoconstriction. Serotonin is also a vasocontrictor, together with TxA2 stimulate smooth muscle contraction and further decrease the size of the site of injury. ADP activates more platelets and exposes GPIIa/IIIb receptors allowing thrombocyte linkage. Platelets attach to each other with receptor GPIIa/3b but require fibrinogen as the linking molecule. Bleeding stops once enough platelets attach to the site of injury and to each other forming the primary platelet plug.
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* Kenneth Kaushansky, Ernest Beutler, Uri Seligsohn, Marshall A. Lichtman, Thomas J. Kipps, Josef T. Prchal. “Williams Hematology” 8th Edition. Mcgraw Hill. 2010. Pg 2779-2821.
* Vinay Kumar, Abul K. Abbas, Nelson Fausto, Jon C. Aster. “Robbins and Cotran Pathologic Basis of Disease” 8th Edition. Saunders Elsevier. 2010. Pg 488-492.