Coagulation Mechanism--Secondary Hemostasis

the system through which coagulation factors interact to eventually form a fibrin clot

what is the fibrin-forming system?

reinforce the platelet plug

what is the purpose of the fibrin clot formation?

secondary hemostasis

what is the fibrin clot associated with?

primary hemostasis

what is the platelet plug associated with?

liver

where are most of the plasma coagulation factors produced?

• Factor II

• Factor VII

• Factor IX

• Factor X

which plasma coagulation factors are part of the Vitamin K group?

a catalyst for the last stage of production of the factors

what does Vitamin K act as?

the plasma coagulation factors will not function properly

• unable to bind to calcium, making them unable to participate in the coagulation reaction

what happens if vitamin K is deficient from diet or is destroyed in the gut flora?

a vitamin K antagonist

what is the Principle of Warfarin/Coumadin Therapy?

• Factor I

• Factor II
  Factor V

• Factor VIII

• Factor XIII

which plasma coagulation factors are part of the consumable group?

in the clot formation—consumed during coagulation

when are the consumable group factors bound?

no

are the consumable group factors present in serum?

Factors V and VIII

which consumable group factors are labile in plasma?

Factor VIII

which consumable group factor deteriorates more rapidly than other coagulant factors?

• soluble plasma proteins

• activated by thrombin

• inactivated by protein C

what characterizes Factor V and VIII?

intrinsic accessory pathway protein

what is the contact group also referred as?

• Factor XI

• Factor XII

which factors are part of the contact group?

initiate coagulation, fibrinolysis, and inflammation—activated by contact with collagen and basement membranes of subendothelial tissue

what is the function of the contact group?

fibrinogen

what is the nomenclature of Factor I?

prothrombin

what is the nomenclature of Factor II?

tissue thromboplastin (tissue factor)

what is the nomenclature of Factor III?

calcium

what is the nomenclature of Factor IV?

labile factor (proaccelerin)

what is the nomenclature of Factor V?

stable factor (serum prothrombin conversion accelerator)

what is the nomenclature of Factor VII?

anti-hemolytic factor (AHF)

what is the nomenclature of Factor VIII?

Christmas factor (plasma thromboplastin component)

what is the nomenclature of Factor IX?

Stuart-Prower Factor

what is the nomenclature of Factor X?

plasma thromboplastin antecedent

what is the nomenclature of Factor XI?

Hageman factor (contact factor)

what is the nomenclature of Factor XII?

fibrin stabilizing factor

what is the nomenclature of Factor XIII?

high molecular weight kininogen

what is the nomenclature of Fitzgerald factor?

pre-kallikrein

what is the nomenclature of Fletcher factor?

the process of blood coagulation involves a series of biochemical reactions that transforms circulating blood into an insoluble gel through the conversion of fibrinogen to fibrin

what is the Coagulation Cascade Theory?

Xlla by contact with collagen or basement membrane

According to the Cascade Theory, what is Factor XII converted to?

each factor acts first as substrate and then as a proteolytic enzyme

what happens once the cascade starts?

• collagen

• calcium

• PF3 phospholipid from the platelet

  • factor XII is first activated

what does the intrinsic pathway require?

• calcium

• tissue thromboplastin to activate factor VII

what does the extrinsic pathway require?

calcium

what is the cofactor for both pathways of the coagulation cascade?

coagulation cannot proceed at a normal rate, initiation of the next subsequent reaction is delayed, time required for the clot to form is prolonged

what happens if there is a deficiency in any one of the factors with the coagulation cascade?

• Factor X

• Factor V

• Factor II

• Factor I

which factors are part of the common pathway?

factors X and V causes factor II to become thrombin—thrombin causes fibrinogen to form fibrin; factor XIII makes fibrin insoluble

what occurs during the common pathway?

the generation of thrombin—thrombin converts soluble fibrinogen to insoluble fibrin

what is the end result of activation of either the intrinsic or extrinsic pathway?

the bioregulation of hemostasis in both normal and pathologic conditions

what does thrombin have a central role in?

• converts fibrinogen to fibrin

• activates factor XIII

• enhances activity of factors V and VIII

• induces platelet aggregation

• binds to thrombomodulin to activate the protein C pathway to suppress coagulation

• activates TAFI to suppress fibrinolysis

what are the functions of thrombin?

a proteolyic enzyme that cleaves bonds on the fibrinogen molecule

what is fibrin?

the kinin system and fibrinolysis

what does Factor VII also activate?

• produces bradykinins

• aids in vasoconstriction

• lowers blood pressure

• produces local pain

• increases capillary permeability that aids in inflammation

what is the importance of the Kinin System?

• Tissue Factor Pathway Inhibitor

• Anti-thrombin III

• Alpha1 antitrypsin and alpha 2 macroglobulin

• protein C and S

what are the inhibitors at each step of coagulation to prevent too much clotting?

activated proteins

what does the liver clear to prevent too much clotting?

binds to Xa; TFPI:Xa complex binds to Vlla—prevents further activation of X and IX

how does the Tissue Factor Pathway Inhibitor (TFPI) inhibit coagulation?

when coagulation is initiated and Factor X is activated

when does TFPI become actively engaged?

coagulation regulatory protein

what is anti-thrombin III?

• Factor II (thrombin)

• Factor IX

• Factor X

• Factor XI

• Factor XII

• prekallikrein

• plasmin

what does anti thrombin III bind and neutralize?

degrade factors V and VIII through interaction with a vessel substance called thrombomodulin as well as thrombin

what is the function of protein C and S?

venous thrombosis events

what is a deficiency in protein C or S associated with?

the process of destroying the clot starts as soon as the clot forms

what is fibrinolysis?

a complex molecule consisting of two individual parts—large fraction: VIII:vWF, smaller fraction: VIII:C

what is Factor VIII/vWF?

endothelial cells and megakaryocytes

what produces the large fraction of Factor VIII (VIII:vWF)?

platelet adhesion

what is VIII:vWF responsible for?

autosomal inheritance

what inheritance pattern does VIII:vWF exhibit?

liver

what produces VIII:C?

intrinsic pathway

when is VIII:C used?

sex-linked inheritance

what inheritance pattern does VIII:C exhibit?

VWF

what stimulates the production of VIII:C?

VIII:C is also low

what happens if vWF is low or absent?

normal vWF levels, but diminished Factor VIII:C levels

what do patients with Hemophilia A exhibit?