Coagulation Cascade Flashcards
Coagulation Factors
Most are formed in the liver in precuror forms by vitamin-K dependent process
What does the Vitamin-K process do?
- Attaches calcium-binding prosthetic groups on the amino terminal regions of these factors
- Introduction of an extra COOH group on the side chain of several glutamic acid residues
- Called gamma-carboxyglutamic acid
Absence of Vitamin-K
- Factors 2,7,9,10 are incomplete, lacking the special calcium-binding gamma-carboxyglutamic acids and appear as nonfunctional factors
- Known as PIVKA (protein induced by vitamin K absence/antagonism)
What factors are synthesized by the Liver?
1,2,5,7,9,10,11,12
Four Stages in blood clotting
- Generation of Prothrombin Activator
- Conversion of Prothrombin to Thrombin
- Conversion of Fibrinogen to Fibrin
- Stabilization of Fibrin
Stage 1 (Clotting)
Extrinsic and intrinsic pathways converge at the final point in stage I where factor X reacts with V to produce prothrombinase
Stage 2 (Clotting)
Conversion of prothrombin (II) to thrombin by prothrombinase
Stage 3 (Clotting)
Consists of the catalytic conversion of fibrinogen to fibrin by thrombin (enzyme)
Stage 4 (Clotting)
Factor XIII acts to stabilize the unstable fibrin
Factor I
Fibrinogen
Factor II
Prothrombin
Factor III
Tissue Thromboplastin
Factor IV
Ionized Calcium
Factor V
Labile Factor or proaccelerin
Factor VII
Stable Factor or proconvertin
Factor VIII
Antihemophilic factor
Factor IX
Plasma Thromboplastin Component or the Christmas Factor
Factor X
Stuart-Prower factor
Factor XI
plasma thromboplastin antecedent
Factor XII
Hageman factor
Factor XIII
fibrin-stabilizing factor
Describe the activation of the intrinsic coagulation pathway
- Damage exposes basement membrane collagen
- Exposed collagen causes activation of Factor XII
a.) Factor XIIa initiates the intrinsic coagulation pathway - Exposed collagen binds von Willebrand factor (vWf)
What is the function of vWf?
Stabilizes platelet binding to collagen via a platelet membrane receptor
Describe the intrinsic pathway coagulation sequence
- Factor XIIa converts Factor XI to factor Xia
- Factor XIa converts Factor IX to factor IXa
- Factor IXa converts factor VIII to Factor VIIIa
- Factor VIIIa activates the common pathway by converting Factor X to Factor Xa
Describe the extrinsic pathway coagulation sequence
- Damaged tissue cells secrete Tumor Necrosis Factor (TNF)
- TNF causes endothelial cells, vascular smooth muscle cells, and fibroblasts to externalize adhesion receptors
- TF converts Factor VII to Factor VIIa
- Factor VIIa converts Factor X to Factor Xa, activating the common pathway
Describe the common pathway coagulation sequence
- Factor Xa converts Prothrombin to thrombin
- Thrombin converts Factor V to Factor Va, which assists in converting prothrombin to thrombin
- Thrombin converts Fibrinogen to fibrin
- Thrombin converts Factor XIII to Factor XIIIa
