Ap Ii: Principles Of Hemostatsis

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AP II: PRINCIPLES OF HEMOSTATSIS

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AP II: PRINCIPLES OF HEMOSTATSIS

Front 2

3 Phases of hemostasis

Back 2

1. formation of platelet
2. coagulation
3. fibrinolysis

Front 3

Formation of platelet plug involves what?

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1. adhesion
2. activation
3. aggregation

Front 4

In the adhesion stage, what does platelet bind to?

Back 4

1. collagen via glycoprotein VI receptor and alpha-beta integrin.

2. vWF via glycoprotein Ib receptor complex.

Front 5

What factor does vWF protect?

Back 5

Factor VIII from rapid inactivation.

Binds platelet via glycoprotein Ib receptor complex.

Binds to collagen via A3 domain.

Front 6

What makes vWF bind to platelets?

Back 6

Change in shear rate.

Front 7

What does vWF disease manifested as?

Back 7

Impaired platelet function.

NOTE: deficiency in vWFactor

Front 8

What is the treatment for vWF disease?

Back 8

Transfusion of FFP or cryoprecipitate or Humate-P which is a Factor VIII concentrate

Front 9

What can desmopressin be used for?

Back 9

Release of vW factor.

Front 10

In activation stage, how are platelets activated?

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They become activated by agonists at site of injury-- collagen, thrombin, ADP, and EPI

Front 11

What contents of alpha granules and dense granules are released during platelet activation?

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1. ADP
2. serotinin
3. Factor V
4. Factor VIII
5. vWF
6. fibrinogen

Front 12

What substance synthesized in cytosol is also released into environment?

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Thromboxane A2

Front 13

What happens to the morphology during plate activation?

Back 13

They change

Front 14

What type of receptors are on the surfaces during platelet activation?

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Negatively charged receptors

Front 15

During the platelet aggregation stage, how is it mediated?

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Mediated by the platelet surface receptor-- glycoproteins IIb/IIIa receptor.

Front 16

In the platelet aggregation stage, what are the adhesive molecules?

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1. fibrinogen
2. vWF

Form bridges btw platelets to create a platelet plug.

Front 17

Char of coagulation factors?

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1. involves interaction of many plasma proteins-"coagulation factors"
2. circulate as "zymogen"
3. zymogen must be cleaved in order to "activate" coagulation factor.
4. requires presence of negatively charged phospholipid membrane.

Front 18

Where are most coagulation factors synthesized?

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Liver

Front 19

Which factors are Vit K dependent factors?

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II, VII, IX, and X

Front 20

Which factor has the extra hepatic origin?

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VII

Front 21

What is the function of Vit K?

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Catalyzes the carboxylation of glutamic acid to become gamma carboxyglutamic acid.

Possible for the factor to bind to Ca.

Front 22

What inhibits carboxylation of vit K dependent factors?

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Coumadin

Front 23

Which factor has the shortest half life of the vitamin K dependent factors?

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VII

Front 24

Hemophilia A has deficiency of which factor?

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VIII

NOTE: it's an X-Linked trait.

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Hemophilia B has deficiency of which factor?

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IX

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What are the actions of thrombin?

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1. cleavage of fibrinogen to fibrin.
2. activates XIII to cross link fibrin.
3. activates platelets
4. activates V, VII, VIII, IX
5. stimulate cells to produce TF and vWF

Front 27

What is the cascade model of coagulation?

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1. series of proteolytic reactions
2. coagulation factors direct and control the process.
3. cells serve as surface on which coagulation complexes are assembled.

















.

Front 28

What are the three overlapping stages of cell based model of coagulation?

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1. Initiation: thrombin initiating the coagulation process.
2. Amplification: Platelets and coagulation factors are activated.
3. Propagation: large amounts of thrombin are generated on the activated platelet surface.
3.

Front 29

Functions of thrombin?

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1. cleaves fibrinogen to fibrin
2. actives platelets
3. activates factors V, VII, VIII, IX
4. stimulates cells to produce TF and vWF.

Front 30

Function of aspirin?

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Acetylates fibrinogen causing clot structure to be looser and easier to lyse.

Does it block formation of thromboxane?

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What takes place in the regulation of coagulation?

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Tissue factor pathway inhibitor (TFPI)

Antithrombin

Protein C

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What's the function of TFPI?

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Inhibits TF/FVIIa complex and TF/FVIIa/FXa complex.

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What's the function of Antithrombin?

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Inhibits FXa and thrombin

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What is the function of Protein C?

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With Protein S (PS), they inhibit FVa and FVIIIa

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Heparin

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Binds to AT and changes it to inhibitor of thrombin.

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Function of plasmin?

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Degrades fibrin

NOTE: formed from plasminogen being activated by tissue plasminogen activator.

Front 37

Describe neonates' hemostatic system and their levels of procoagulant and anticoagulant factors.

Back 37

They have a well balanced efficient system, but with low levels of the factors.

Front 38

Neonates vs. adults in
1. platelet counts
2. platelet dense granules
3. platelet aggregation in response to ADP, EPI, collagen, and thrombin.

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Platelet counts: 100% of adults

Contents of platelet dense granules: 50% of adults

Platelet aggregation is impaired.

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What are the qualitative differences of neonates' fibrinogen vs. adults?

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1. different chemical structure
2. dec. rate of fibrin polymerization
3. fibrin clot char by lower density.

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In a nutshell, fetal form of fibrinoge:

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1. exists until 1yr old
2. fibrin clots are less dense.

Front 41

Plasminogen of neonates:

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Lower concentration: 50% of adults.

Decreased functional activities (i.e. fibronolytic activity).

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In conclusion, cell based model of hemostasis provides?

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An in vivo model of coagulation process.

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Neonates' hemostatic system

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Shows an intact and functioning system.