Intrinsic & Extrinsic Clotting Cascades:
Coagulation: a multistep process: Step 1:
Formation of prothrombin activators --> EXTRINSIC & INTRINSIC pathways
Factor XII is exposed to endothelial collagen and becomes Factor XIIa, an activated serine protease. A cascade of clotting factors follows and includes Factor XI, IX and X. Which factor displays the highest concentration throughout this progression?
X *As the cascade progresses, the concentrations of factors are increased relative to preceding factors. The progression of factors as listed within the intrinsic pathway is XII, XIIA, XI, XIA, IX, IXA, X, XA. Factor X has a higher concentration than factors IX, XI, and XII.
Vitamin K:
a major player in synthesis of 4 clotting factors
Coagulation-
process that occur simultaneously with the formation of the platelet plug
Primary hemostasis:
results in the formation of a soft platelet plug, involves vasoconstriction, platelet adhesion, platelet activation, and platelet aggregation.
Platelet Aggregation:
the process by which platelets stick together, stimulated by the von willebrand factor
Fibrinolysis:
-removes blood clot after wound healing -plasmin digests fibrin strands -begins 2 days after clot formation -happens by use of plasmin (tissue plasminogen activator XIIa & IIa (TPA) plasminogen--> plasmin
What molecule is a naturally occurring anticoagulant?
Antithrombin -Antithrombin is a serine protease inhibitor that inactivates thrombin, factor IXa, factor Xa, factor Xia, and factor XIIa, all of which are involved in the coagulation cascade.
Hemostasis:
Complex& fast reaction response to blood loss -Prevents blood from leaving damaged vessels -Composed of: vascular spasm platelet plug formation coagulation
Under normal circumstances platelets do not stick to each other or endothelial surface because..
Endothelial cells produce anti-aggregation chemical compounds such as nitric oxide and PGI2 or prostacyclin
What clotting factor specifically involves the common pathway?
Factor II
Prothrombin activator complex
Factor Xa Factor Va Platelet factor 3 Calcium ions
Step III: formation of the fibrin mesh:
Fibrinogen -Thrombin (IIa)-> fibrin monomers -fibrin monomers polymerize insoluble long fibrin strands -Result: loose fibrin mesh that traps circulating blood cells -blood turns into a gel-like paste -XIIIa is a cross linking enzyme -cross-links the fibrin strands -tightens the fibrin web
Once the clot is formed, and healing takes place you eventually want to remove it called
Fibrinolysis
Vascular Spasm:
First response to a blood vessel injury Triggers: -early- nervous reflexes -late- vasoconstrictors (TXA2, serotonin, adenosine) Effectors: -smooth muscle cells
Coagulation: a multistep process: Step 3:
Formation of the fibrin mesh (COMMON pathway)
An important receptor for this process:
GPIIB/GPIIIa complex is phosphorylated and therefore activated. This receptor allows fibrinogen to form a platelet plug
Clotting Factors:
I.Fibrinogen II. Prothrombin III. Tissue Factor IV. Calcium ions XIII. Fibrin stabilizing factor
Step 1: prothrombin activators:
Initiation: intrinsic & extrinsic Involves both the activation of factor X and the formation of the prothrombin activator complex
Von Willebrand factor & aggregation
Large plasma protein Forms bridges btwn -subendothelial collagen & platelets -platelet & platelet Activated when collagen is exposed to blood stream Mediates platelet aggregation process
Coagulation
Multi-step process Reinforces the previous plug Creates a sturdy fibrin mesh Blood turns into a gel capable of sealing lg wall defects Produced by interaction of clotting factors
Clotting factors:
Plasma proteins, synthesized by the liver, that are essential to the clotting response. -Numbered from I- XII -Normally inactive in blood stream - Each factor, once activated acts on the next one in an orderly fashion -Final result: fibrinogen turns into fibrin
During trauma or injury, the body initiates the repair of the damaged tissue. What cells are responsible for developing a mesh-like clot to prevent further loss of blood?
Platelets
Coagulation: a multistep process: Step 2:
Prothrombin activation (COMMON pathway)
Step II: Prothrombin Activation
Prothrombin activator complex: -factor Xa (intrinsic & extrinsic pathways) -factor Va (activated by Xa) platelet factor 3 (released in the aggregation process) -calcium ions Common pathway -prothrombin--> thrombin
Hemostasis is the physiological response that stops bleeding at the site of an injury. What is the function of insoluble fibrin?
Stabilize the blood clot *Insoluble fibrin is a component of secondary hemostasis, which strengthens and stabilizes the blood clot.
What clotting molecule is exclusively linked to the extrinsic pathway?
Thromboplastin
Extrinsic pathway
Trigger- blood exposure to subendothelial tissue, containing tissue factor (III) factor 7, 10 -The main clotting factor is outside the blood vessel (EXtrinsic) -faster than intrinsic pathway
Intrinsic Pathway
Trigger: negatively charged surfaces -Clotting factors are within the vessel (INtrinsic) 12, 11, 9 & 8a -more factors involved -more intermediate sequences -slower
platelet plug formation
Triggered by exposure of platelets to collagen Platelets adhere to rough surface to form a plug. Temporary closure of the wall defect
Intrinsic and Extrinsic pathways
both processes take place simultaneously and are strongly dependent on each other
Secondary hemostasis:
defined as the formation of fibrinogen into fibrin, which ultimately evolves the soft platelet plug into a hard, insoluble fibrin clot.
Clotting factors involved in extrinsic pathway:
factor VII, and III.
Clotting factors involved in common pathway:
factor X, V, II, I, and XIII
Clotting factors involved in intrinsic pathway:
factors XII, XI, IX, and VIII.I
once platelets bind to von willebrand factor..
molecular pathways activate the cells to change their shape to more efficiently seal the wall becoming stickier and forming a spike process that helps aggregation
Platelet Activation:
volume & shape changes leading to formation of membranous spikes