II. Platelets (aka. Thrombocytes):

III. Blood Clot (web of fibrin that surrounds the platelet plug)

- usually occurs in a vein (99% of superficial vessels are veins and they are under lower pressure). - Plugs and clots in arteries are usually destroyed quickly by the high pressure. Clots are fragile for the first 45 min to 1 hour (direct pressure to a wound gives the factors time to form a stable clot). - Clot formation depends on the filamentous protein fibrin.

intrinsic pathway - intrinsic because all factors required are continually circulating in the plasma. This is in response to a specific cut, localized damage and when plasma encounters a negatively charged surface (i.e., collagen). Process takes 2-5 minutes.

1. Factor XII (Hageman factor) is activated; 2. XII activates XI (Plasma thromboplastin antecendet); 3. XI activates IX (Plamsa thromboplastin component); 4. IX combines specifically with VIII (antihemophilic factor), Ca2+ and phospholipids to form VIII complex 5. VIII complex activates X (common pathway).

II. Extrinsic pathway - activated during blunt force trauma and wide spread damage. Takes 15-30 seconds to complete (skips steps)

1. damaged cells release factor III (tissue thromboplastin). 2. III activates VII (Proconvertin) 3. III and VII, combine with Ca2+ and phospholipids to create the VII complex (prothrombin activator). 4. VII complex activates x (common pathway).

Von Willebrand's factor

Endothelial cells also prepare the basement membrane collagen to better support the formation of a platelet plug by secreting the glycoprotein Von Willebrand's factor, which binds to collagen and to platelets to form a very strong first layer of platelets adhering to the collagen and resisting the hydrodynamic force of the flowing blood.

Fibrin( 2nd step)

Fibrin then contracts the entire mass (clot retraction) to form a more compact clot and to bring the edges of the wound closer together. To prevent the premature formation of a fibrin web (clot), fibrin is circulated as an inactive precursor fibrinogen, that must be activated to form a clot.

Fibrin (1st step):

Fibrin, once polymerized into a meshwork, is very sticky and causes platelets to stick, RBCs, WBCs forming a denser clot. The clot becomes stabilized by "crosslinking" all the proteins together via factor 13.

Fibrin activation (common pathway)

Fibrinogen is converted to fibrin via an activation cascade as follows: 1. Factor X (Stuart-Prower Factor) becomes activated either via an intrinsic or extrinsic pathway (see below). 2. X combines with factor V (Proaccelerin), calcium and phospholipids to form the V complex (prothrombin activator). 3. This enzymatically cleaves amino acids from inactive prothrombin into the activated form, thrombin. 4. Thrombin converts fibrinogen into fibrin to initiate clot formation.

Response to Vascular Damage

I. Vascular spasms (vasoconstriction) II. Platelet plug formation -platelet release reaction III. Blood Clot (web of fibrin that surrounds the platelet plug) aka. Coagulation: 1Fibrin A.Fibrin activation i.Intrinsic pathway ii. Extrinsic pathway

Kallikrein

Over time, as the vessel heals, XII activates ----- (plasminogen activator), which converts plasminogen into the active plasmin. Plasmin digests fibrin into small chains, leading to the dissolution of the clot.

II. Platelets (aka. Thrombocytes): Thrombopoiesis

Platelets are produced in myeloid tissue by large cells called megakaryocytes. These cells respond to the cytokine thrombopoietin to shed cellular fragments (platelets) into the circulation. - 130-400K per cubic ml of blood (normal range). - Thombocytopenia (low platelet counts). - 5-9 day lifespan - Also destroyed in liver and spleen. Platelets function in the formation of a platelet plug (the initiation of a blood clot) as well as in the secretion of materials essential for blood vessel integrity.

Factor 13

The clot becomes stabilized by "crosslinking" all the proteins together via factor 13.

II. Platelet plug formation

The endothelial cells of blood vessels prevent the activation of platelets by: - being a physical barrier to the underlying supportive collagen and other basement membrane/connective tissue molecules. Endothelial cell surface is (-) and platelets are also (-). - Secreting prostacyclin and nitric oxide, which are vasodilators and inhibit platelet activation. - Expressing CD39, an enzyme that converts ADP (an activator of platelets) into AMP.

Hemostasis

is the cessation of blooding.

Platelet release reaction:

platelets activate in response to various signals in the circulatory system, including, encounter with collagen/Von Willebrand's factor. This activation leads to the "Degranulation" of the vesicles present in the platelets which contain: - ADP - Serotonin - vasoconstrictor. - Thromboxane A - activates platelets and vasoconstrictor. These cause the platelets to become "sticky" and signal other platelets to do the same, creating layer upon layer of platelets in the plug. Platelets also bind to fibrinogen and fibrin, which initiates the formation of the third hemostasis mechanism: blood clotting

I. Vascular spasms (vasoconstriction) -

rapid and temporary limitation to blood flow caused by the contraction of smooth muscles in response to trauma.