Hemostatic Mechanism From Chapter 8 Of Barash's Clinical Anesthesia

Front 1

What event activates the coagulation process?

Back 1

Exposure of blood to the membrane-bound protein Tissue Factor, generally 2/2 a breach in the vascular endothelium.

Front 2

What does Tissue Factor activate?

Back 2

TF activates the coagulation process in general; it does so specifically by activating circulating Factor VII to yield a TF-VIIa complex that includes a phospholipid surface (TF has been bound to that surface the whole time).

Front 3

What does the TissueFactor-VIIa complex do?

Back 3

It activates Factors IX and X.

Front 4

What activates Factor X?

Back 4

Factor X is activated by the TF-VIIa phospholipid bound complex.

Front 5

What does Factor Xa do?

Back 5

Factor Xa activates factor V to form the "prothrombinase complex" composed of Factor Xa and Va on a phospholipid surface provided by Tissue Factor.

Front 6

What is the Prothrombinase Complex?

Back 6

It is a phospholipid surface with two bound complexes. The first is TF-VIIa and the more important final complex is Xa-Va.

Front 7

What does the Prothrombinase Complex do?

Back 7

It catalyzes the initial conversion of prothrombin (FII) to thrombin (FIIa) in the activation portion of the coagulation cascade.

Front 8

What are the three phases of coagulation?

Back 8

1) Activation
2) Amplification
3) Propagation

Front 9

During the time that Activation of coagulation occurs, a concurrent event happens that primes the 2nd stage. What is that event?

Back 9

The breach in the vascular tree that exposed Tissue Factor to factor VII, also exposed collagen. Circulating vWF binds to this collagen and in turn platelets become bound to the VWF via the GPIb receptor on the platelet surface. This changes the shape of the platelet from discoid to spheroid with extruding pseudopods (essentially blebs).

Front 10

What provides the phospholipid surfaces in coagulation?

Back 10

1) Tissue Factor in Activation
2) Platelets in Amplification and Propagation

Front 11

How does thrombin support the amplification of the coagulation process?

Back 11

1) Promotes GPIIIb/IIa receptors and release of platelet granules
2)promote activation of V
3)releases VIII from vWF and activates it
4) activates XI

Front 12

What is the net result of the Amplification stage of the coagulation process?

Back 12

Increased availability of activated platelets, Va, VIIIa and IXa.

Front 13

How does Factor VIII get activated?

Back 13

It must first be released from its carrier molecule vWF by thrombin. Thrombin then also activates it.

Front 14

What are two of the contents of the platelet granules in the coagulation process?

Back 14

ADP and Factor V.

Front 15

What activates Factor V?

Back 15

Factors Xa (important in the activation of coagulation) and Thrombin (important in the amplification of coagulation)

Front 16

What activates Factor XI?

Back 16

Thrombin

Front 17

What does Factor XIa do?

Back 17

Activated Factor XI activates Factor IX.

Front 18

What activates Factor IX?

Back 18

Activated Factor X and Activated Factor XI.

Front 19

What does activated Factor IX do?

Back 19

It combines with VIIIa to form the Tenase Complex on a platelet-derived phospholipid surface. The complex activates activates X.

Front 20

What is the Tenase Complex?

Back 20

It is a complex of activated factors VIIIa and IXa on a platelet-derived phospholipid surface that activates Factor X.

Front 21

What role to ADP play in the coagulation cascade?

Back 21

ADP, released from platelets, is a powerful platelet activator and proaggregant.

Front 22

What activates Fibrinogen?

Back 22

Thrombin

Front 23

What do fibrinogen and fibrin do?

Back 23

They crosslink platelets to strengthen the structural integrity of platelet plugs.

Front 24

How does thrombin stabilize a fibrin clot?

Back 24

1) activating fibrinogen
2) activating Thrombin Activatable fibrinolysis inhibitor
3) activating XIII (fibrin stabilizing factor)

Front 25

What does FXIII do once activated?

Back 25

It converts soluble fibrin fibers held together by weak hydrogen bonds to insoluble fibrin fibers held together by covalent peptide bonds. This is why it is called fibrin stabilizing factor

Front 26

What role does the GPIIb/IIIa receptor on platelets play?

Back 26

It is the anchor on both ends of a fibrin or vWF cross-linking bridge connecting two platelets.

Front 27

What are the different types of platelet granules?

Back 27

Alpha and dense

Front 28

What is in the alpha granules of platelets?

Back 28

1) vWF
2) Fibrinogen
3) Fibronectin
4) Thrombospondin
5) PDGF
6) Factors V, XI
7) Protein S
8) PAI

Front 29

What is in the dense granules of platelets?

Back 29

1) ADP
2) ATP
3) Serotonin
4) Histamine
5) Ca++

Front 30

What causes platelets to release their granules?

Back 30

1) changing shape as happens when bound to vWF
2) exposure to epinephrine
3) exposure to ADP
4) exposure to thrombin

Front 31

What factor probably has some extrahepatic synthesis?

Back 31

Factor VIII

Front 32

What are the two roles of vWF?

Back 32

1) mediating adhesion of platelets to collagen
2) serving as the carrier molecule of the coagulant portion of Factor VIII (Factor VIII:C)

Front 33

Describe circulating Factor VIII.

Back 33

Very large complex with a HMW component consisting of VIIIR:Ag and vWF. vWF has attached to it a smaller component, XIII:C which is the actual part of XIII that has coagulating activity.

Front 34

What hemostatic abnormalities are caused by the absence of vWF?

Back 34

1) failure in primary hemostasis because of failure of platelet adhesion to collagen
2)clinical hemophilia A because of an absence of circulating VIII:C

Front 35

What part of the factor VIII complex does the lab test for?

Back 35

VIIIR:Ag, the part that does not take part in coagulation?

Front 36

Where is vWF synthesized?

Back 36

endothelial cells and megakaryocytes

Front 37

Where is factor VIII:C synthesized?

Back 37

No one knows...perhaps in the hepatic sinusoidal endothelial cells

Front 38

What does absence of factor VIII:C cause?

Back 38

Hemophilia A

Front 39

What four clotting factors are VitK dependent?

Back 39

II, VII, IX and X require VitK for completion of synthesis in the liver (i.e., the addition of a carboxyl group that enables them to bind to phospholipid surfaces)

Front 40

What does VitK enable the VitK dependent coagulation factors to do?

Back 40

It enables factors II, VII, IX, X to adhere to a phospholipid surface without which they cannot function.

Front 41

What is the first clotting factor to become dysfunctional when a patient is placed on warfarin or is VitK deficient?

Back 41

Factor VII because it has the shortest half-life.

Front 42

What are the "labile factors" of the coagulation factors?

Back 42

Factors V and VIII because their coagulant activity is not durable in stored blood.

Front 43

Which factors do not retain their coagulant activity in stored blood?

Back 43

Factors V and VIII.

Front 44

What does VitK do chemically for the Vit-K dependent coagulation factors?

Back 44

It is the enzyme that enables a final carboxylation of factors II, VII, IX and X without which they could not adhere to phospholipid surfaces.