Blood Coagulation

Question 1

Primary Mechanisms for Hemostasis

1.) ____ ____

___ incorporation into the PLATLELET PLUG

2.)____–> ___ ___

____, aggressive enzyme

That captures the RBC and begins the clot

HemCon Dressings -____ wound and permit ____

QuickClot Combat Gauze—recommended for soldiers___ wounds and has saved many soldiers lives. Both are useful as an ____ barrier

Answer 1

Primary Mechanisms for Hemostasis

1.) PLATELET AGGLUTINATION

Fibrin incorporation into the PLATLELET PLUG

2.) FIBRINOGENà INSOLUBLE FIBRIN

Thrombin, aggressive enzyme

That captures the RBC and begins the clot

HemCon Dressings —seal wound and permit coagulation

QuickClot Combat Gauze—recommended for soldiers hemorrhaging wounds and has saved many soldiers lives. Both are useful as an antibacterial barrier

Question 2

The Clinical Benefit of a Blood Clot

Reduce ___ ___ ( HemCon dental dressings ? )

Prevent ____ of exposed tissue

Reduce ____ invasion

____ and hold ruptured tissue

Serves as a ____ for epithelium

Very important in ____ injuries

Answer 2

The Clinical Benefit of a Blood Clot

Reduce blood loss- ( HemCon dental dressings ? )

Prevent dehydration of exposed tissue

Reduce bacterial invasion

Strengthen and hold ruptured tissue

Serves as a Bridge for epithelium

Very important in repairing injuries

Question 3

Overview of common Hemorrhagic Disorders

1. )_____ bleeding—(nose, gingiva, urinary, rectal
   a. “In the U.S. superficial bleeding most often is _____ (Decrease in platelets), but mild ___ ____ is very common”.
   b. Abnormalities of vessel wall and ____ platelet disorders are less common. But if they occur they can lead to superficial bleeding
2. )____ bleeding– Congenital deficiency of factors ___ and ___

They bleed into their ____ and their joints become stiff

3.)__ ___ bleeding - due to ___ or ___, usually a deficiency of factors ___ and ____

Answer 3

Overview of common Hemorrhagic Disorders

1. )Superficial bleeding—(nose, gingiva, urinary, rectal
   a. “In the U.S. superficial bleeding most often is thrombocytopenia (Decrease in platelets), but mild von Willebrand is very common”.
   b. Abnormalities of vessel wall and qualitative platelet disorders are less common. But if they occur they can lead to superficial bleeding
2. )Deep bleeding– Congenital deficiency of factors VIII & IX. (8 and 9)

They bleed into their joints and their joints become stiff

3.)Non spontaneous bleeding - due to trauma or surgery, usually a deficiency of factors XI & XIII. (11 and 13)

Question 4

POINTS/HEMOSTASIS

QUANTITY OF PLATELETS- _____

PLATELET QUALITY- Defect –____

Same symptoms but different cause

Billy Crystal- Drilling for laughs

“ I don’t have tartar, I have coral”

“You could sculpt Michelangelo’s “David out of my plaque”

You never hear “is there a dentist in the house”

Answer 4

POINTS/HEMOSTASIS

QUANTITY OF PLATELETS- THROMBOCYTOPENIA

PLATELET QUALITY- Defect –Thrombasthenia

Same symptoms but different cause

Billy Crystal- Drilling for laughs

“ I don’t have tartar, I have coral”

“You could sculpt Michelangelo’s “David out of my plaque”

You never hear “is there a dentist in the house”

Question 5

Endothelium Antihemostatic/ Antithrombotic

Obj #1A- Identify the major mechanisms of non-injured endothelial cells which maintains blood in a fluid state.

a.) ____ ___, ____

Are produced by the ____ cells,

They are vas____ and inhibit ___ ____ .

(Note- both limit clot size.) Note slide Fig 11-11

Prevent clot spreading to non-injured endothelial cells

b.) ____

______

Combines with ____ ____

Together they bind to ____ to reduce its action on ____

Answer 5

Endothelium Antihemostatic/ Antithrombotic

Obj #1A- Identify the major mechanisms of non-injured endothelial cells which maintains blood in a fluid state.

a.) Prostacyclin I2, NO

Are produced by the endothelial cells,

They are vasodilators and inhibit platelet adhesion.

(Note- both limit clot size.) Note slide Fig 11-11

Prevent clot spreading to non-injured endothelial cells

b.) Heparin

Anticoagulant

Combines with Antithrombin III

Together they bind to thrombin to reduce its action on fibrinogen

Question 6

Prothrombotic/Endothelium

Obj #1B Identify 2 vascular______ derived proteins that adhere to _____ receptors on the platelets.

These are:

a. ___ ____
b. ___ __ ___

____ adheres to glycoprotein receptors but it is DERIVED from the ___

Not derived from endothelial cells like a and b.

Answer 6

Prothrombotic/Endothelium

Obj #1B Identify 2 vascular subendothelial derived proteins that adhere to glycoprotein receptors on the platelets.

These are:

a. Collagen microfibrils
b. Von Willebrand factor

Fibrinogen adheres to glycoprotein receptors but it is DERIVED from the liver.

Not derived from endothelial cells like a and b.

Question 7

Obj. #2 Major Mediators

Identify the metabolic events and major events in the formation of a platelet plug.

2. A Major Prothrombotic mediators
   a. ) ____
   b. ) ___ __ ___
   c. ) ____
   d. )____ ___
   e. ) ____
   f. ) ____, platelet ____ _____- ___ ___ ___
   g. ) Platelet ___ ___/ ___ ___ ___

A decrease in one of these can lead to a prolonged bleeding time

Answer 7

Obj. #2 Major Mediators

Identify the metabolic events and major events in the formation of a platelet plug.

2. A Major Prothrombotic mediators
   a. ) Collagen
   b. ) Von Willenbrand factor;
   c. ) Fibrinogen
   d. )Thromboxane A2;
   e. ) ADP
   f. ) Ca++, platelet membrane phospholipid- Platelet Factor 3 (PF3)
   g. ) Platelet glycoprotein receptors/ cell adhesion molecules (CAM)

A decrease in one of these can lead to a prolonged bleeding time

Question 8

The Role of Platelets

When the surface of the oral mucosa is disrupted or injured, ___ are activated and a fibrin plug is formed which controls the____ and ____ of the tissue can begin.

Obj #2-b Identify 5 EVENTS necessary for Platelet Plug formation

1.) Platelet ____

Platelets going by the injured site have to adhere to the exposed ____

2. ) ___ and __ __ ___
3. ) ____ reaction
4. ) ____

Of platelets that are not adhering, they are just floating by in the blood as it flows thru

5.) ____ Platelet-assisted Coagulation

Answer 8

The Role of Platelets

When the surface of the oral mucosa is disrupted or injured, platelets are activated and a fibrin plug is formed which controls the bleeding and repair of the tissue can begin.

Obj #2-b Identify 5 EVENTS necessary for Platelet Plug formation

1.) Platelet adhesion

Platelets going by the injured site have to adhere to the exposed collagen

2. ) Activation and change in shape
3. ) Secretion reaction
4. ) Recruitment

Of platelets that are not adhering, they are just floating by in the blood as it flows thru

5.) Aggregation Platelet-assisted Coagulation

Question 9

First thing that happens when you have injury is______, which reduces blood flow to prevent blood loss. That’s not much help and it will only last about 15 sec.

1) Platelets adhere to exposed Collagen
2) Then they get a shape change that exposes the ___ ___ (For VWF, Fibrinogen, Thromboxane….)
3) Then you get granule release (___ and ____ and many more)
4) That leads to recruitement of ____ platelets that are just floating by
5) Then you get aggregation and the formation of the___ ___

Answer 9

First thing that happens when you have injury is vasoconstriction, which reduces blood flow to prevent blood loss. That’s not much help and it will only last about 15 sec.

1) Platelets adhere to exposed Collagen
2) Then they get a shape change that exposes the platelet receptors (For VWF, Fibrinogen, Thromboxane….)
3) Then you get granule release (ADP and TXA2 and many more)
4) That leads to recruitement of nonadhered platelets that are just floating by
5) Then you get aggregation and the formation of the platelet plug

Question 10

Platelets aggregate at a vessel defect through a ____ -feedback mechanism involving the release of ___ and ___from ____, which stick to exposed ____ at the site of the injury. Platelets are prevented from aggregating at the adjacent normal vessel lining by the release of ____ and___ ____from the undamaged endothelial cells.

1. )Platelets adhere to and are activated by exposed collagen at the site of vessel injury
2. )Activated platelets release ___ and _____
3. )These chemical messengers work together to activate other____ passing by
4. )Newly activated platelets ___ onto growing platelet plug and ____ even more platelet-attracting chemicals
5. )Normal (uninjured) endothelium releases prostacyclin and NO, which inhibit platelet aggregation, so platelet plug is ____ to site of injury

ADP and A2 also enhance prostacyclin and NO

Answer 10

Platelets aggregate at a vessel defect through a positive-feedback mechanism involving the release of adenosine diphosphate (ADP) and thromboxane A2 from platelets, which stick to exposed collagen at the site of the injury. Platelets are prevented from aggregating at the adjacent normal vessel lining by the release of prostacyclin and nitric oxide from the undamaged endothelial cells.

1. )Platelets adhere to and are activated by exposed collagen at the site of vessel injury
2. )Activated platelets release ADP and thromboxane A2
3. )These chemical messengers work together to activate other platelets passing by
4. )Newly activated platelets aggregate onto growing platelet plug and release even more platelet-attracting chemicals
5. )Normal (uninjured) endothelium releases prostacyclin and NO, which inhibit platelet aggregation, so platelet plug is confined to site of injury

ADP and A2 also enhance prostacyclin and NO

Question 11

Obj #3 Platelet Adhesion

3 - Name 3 types of adhesive proteins that bind to glycoprotein (GP) receptors on the Platelet membrane.

Platelet adhere to foreign tissue, (collagen, oral mucosa, enamel) because of GP receptors.

Answer: _____, ____, _____

Answer 11

Obj #3 Platelet Adhesion

3 - Name 3 types of adhesive proteins that bind to glycoprotein (GP) receptors on the Platelet membrane.

Platelet adhere to foreign tissue, (collagen, oral mucosa, enamel) because of GP receptors.

Answer: Von Willebrand factor, Fibrinogen, Collagen

Question 12

4-b- What is the major site of synthesis and role of Thromboxane A2 in platelet function.

Platelet Activation and Secretion

-Obj #4-a – Identify the physical changes that platelets undergo when activated.

Collagen interacts with platelet and when that occurs you get ___ of the ____

Thromboxane A2 is a derivative of ____ ____ similar to PGE2

Its formed in the ____ and its formed from the membrane _____ from the arachodonic acid that’s there

Major Site of Syn: Arachadonic Acid

It’s synthesized and it acts back on its receptor to cause ___ ____

Recall that thrombocytopenia (Decrease in platelets) is the most common platelet disorder

Thrombasthenia is a minor one but it can occur and it is very hazardous

Answer 12

4-b- What is the major site of synthesis and role of Thromboxane A2 in platelet function.

Platelet Activation and Secretion

-Obj #4-a – Identify the physical changes that platelets undergo when activated.

Collagen interacts with platelet and when that occurs you get exposure of the receptors

Thromboxane A2 is a derivative of arachadonic acid similar to PGE2

Its formed in the platelets and its formed from the membrane phospholipid from the arachodonic acid that’s there

Major Site of Syn: Arachadonic Acid

It’s synthesized and it acts back on its receptor to cause platelet aggregation

Recall that thrombocytopenia (Decrease in platelets) is the most common platelet disorder

Thrombasthenia is a minor one but it can occur and it is very hazardous

Question 13

5 Identify the initial biochemical reaction for the aggregation of activated platelets at the site of trauma.

Obj #5 Platelet Aggregation

Answer- ___ binds to activated uncovered platelet receptors. __ and ___ are required for this conformation or shape change.

Fibrinogen is a ___ protein that comes from the ___

Its i____ in the blood stream.

____ will convert it to Fibrin

Non Objective: Platelet Activation factor

(PAF an active phospholipid that contributes to asthma and endotoxin shock)

PAF will cause a shape change and activation but that’s not its role

Answer 13

5 Identify the initial biochemical reaction for the aggregation of activated platelets at the site of trauma.

Obj #5 Platelet Aggregation

Answer- Fibrinogen binds to activated uncovered platelet receptors. ADP and Ca++ are required for this conformation or shape change.Fibrinogen is a plasma protein that comes from the liver.

Its insoluble in the blood stream.

Thrombin will convert it to Fibrin

Non Objective: Platelet Activation factor

(PAF an active phospholipid that contributes to asthma and endotoxin shock)

PAF will cause a shape change and activation but that’s not its role

Question 14

This shows platelets with receptor for VWF

Platelet adheres to collagen and to VWF thru this receptor

If there is deficiency of VWFà Superficial Bleeding

If there is a deficiency in that receptor leads to same symptoms as decrease in VWF

Another receptor on platelet binds to fibrinogen

Answer 14

This shows platelets with receptor for VWF

Platelet adheres to collagen and to VWF thru this receptor

If there is deficiency of VWFà Superficial Bleeding

If there is a deficiency in that receptor leads to same symptoms as decrease in VWF

Another receptor on platelet binds to fibrinogen

Question 15

6 What is the role of the platelet membrane in blood coagulation?

Platelet Associated Coagulation

Answer- it provides a ____ (called ___ __ ___ ), which binds to various hemostatic ___s and ___ ___. (__ __ __ _ ___)

PF3 (phospholipid surface) has binding site for activated factor _.

This (Antihemopheliac factor) binds to PF3 site

It’s got some places for factor ___ to be seated.

Its bound to PF3 thru ___.

Now we have a serine protease that’s very active and __ sits down next to it. (Kind of like a love seat.

This arouses 10.

10 becomes an active serine protease and then its ____ from this complex

Answer 15

6 What is the role of the platelet membrane in blood coagulation?

Platelet Associated Coagulation

Answer- it provides a surface (called Platelet Factor 3), which binds to various hemostatic cofactors and serine proteases. (VIII & VII, X, IX, and prothrombin)

PF3 (phospholipid surface) has binding site for activated factor 8.

This (Antihemopheliac factor) binds to PF3 site

It’s got some places for factor 9 to be seated.

Its bound to PF3 thru Ca.

Now we have a serine protease that’s very active and 10 sits down next to it. (Kind of like a love seat.

This arouses 10.

10 becomes an active serine protease and then its discharged from this complex

Question 16

von Willebrand Factor: An important hemostatic protein

Obj #7. Identify 2 major actions of this large factor

Answer:

a. ) Essential for the ____ of ___ to ___ and other surfaces.
b. ) Stabilizes and protects Factor ___, the ____ ____

It’s a large protein. It’s a multimer

About 2% of popl is deficient in vWF

It’s the truck that transports the cargo, factor 8

VWF binds to platelets thru receptors, which then bind to fibrinogen and this whole thing aggregates

It’s released from the endothelial cells, gets into the blood stream and binds to factor 8 and protects it from being broken down so quickly.

Answer 16

von Willebrand Factor: An important hemostatic protein

Obj #7. Identify 2 major actions of this large factor

Answer:

a. ) Essential for the adherence of platelets to collagen and other surfaces.
b. ) Stabilizes and protects Factor VIII, the antihemophilic factor.

It’s a large protein. It’s a multimer

About 2% of popl is deficient in vWF

It’s the truck that transports the cargo, factor 8

VWF binds to platelets thru receptors, which then bind to fibrinogen and this whole thing aggregates

It’s released from the endothelial cells, gets into the blood stream and binds to factor 8 and protects it from being broken down so quickly.

Question 17

Most Common Antiplatelet medications

The cyclooxygenase inhibitors (aspirin blocks ____ ____) and the ____ ____ inhibitors (Plavix & Ticlid).

Primary objective of this article : “fear of uncontrolled bleeding has caused dental practitioners to tell their patient to stop aspirin intake for 7 -10 days before any dental surgery procedures.”

Conclusion from these studies; aspirin intake should not be ____, dentist should use ___ hemostatic measures to control superficial oral bleeding. (Like Pressure or Cotton)

Answer 17

Most Common Antiplatelet medications

The cyclooxygenase inhibitors (aspirin blocks TXA2 synthesis) and the adenosine diphosphate (ADP) receptor inhibitors (Plavix & Ticlid).

Primary objective of this article : “fear of uncontrolled bleeding has caused dental practitioners to tell their patient to stop aspirin intake for 7 -10 days before any dental surgery procedures.”

Conclusion from these studies; aspirin intake should not be stopped, dentist should use local hemostatic measures to control superficial oral bleeding. (Like Pressure or Cotton)

Question 18

Obj. #8 Vit K Dependent Clotting Factors

See fig 11-14.

Vitamin K functions as an essential ____ in the hepatic synthesis of 4 factors, ____, ___, ____, ____

This vitamin promotes a modification of ___ ___ to ___-____glutamic acid (Gla), which mediates the binding of the factors to ____

This property permits these 4 factors to be converted from ___ ___ to active ___ ___

Exist in bloodstream as inactive zymogens

Converted to serine proteases when bleeding occurs

NOTE: Anticoagulants, i.e. ____ related compounds, is a Vit K antagonist reduces ___ of these __ __ s by the ___ .)

Patient will bleed longer

Put on this bc patient at threat of thrombosis

Answer 18

Obj. #8 Vit K Dependent Clotting Factors

See fig 11-14.

Vitamin K functions as an essential cofactor in the hepatic synthesis of 4 factors, prothrombin or factor II, factors X, VII, IX.

This vitamin promotes a modification of glutamic acid to gamma-carboxyglutamic acid (Gla), which mediates the binding of the factors to calcium.

This property permits these 4 factors to be converted from inactive zymogens to active serine proteases.

Exist in bloodstream as inactive zymogens

Converted to serine proteases when bleeding occurs

NOTE: Anticoagulants, i.e. warfarin related compounds, is a Vit K antagonist reduces generation of these clotting factors by the liver.)

Patient will bleed longer

Put on this bc patient at threat of thrombosis

Question 19

Figure will be given on exam

Thrombin will cut Fibrinogen to Fibrin (which at this point is a ____ meshwork which captures the RBC)

This is called the common pathway

Factor 10 binds to Ca and is affected by Warfarin because there is Ca right there

Extrinsic Pathway: When the tissue is injured, it releases tissue thromboplastin and factor 7 interacts with Ca and PF3 and its converted to active factor 7

Intrinsic Pathway

Example Question:

Which one of the following is not Vit K dependent clotting factor?

__, __ , ___, ___ is bc there is Ca right there next to it.

Answer 19

Figure will be given on exam

Thrombin will cut Fibrinogen to Fibrin (which at this point is a loose meshwork which captures the RBC)

This is called the common pathway

Factor 10 binds to Ca and is affected by Warfarin because there is Ca right there

Extrinsic Pathway: When the tissue is injured, it releases tissue thromboplastin and factor 7 interacts with Ca and PF3 and its converted to active factor 7

Intrinsic Pathway

Example Question:

Which one of the following is not Vit K dependent clotting factor?

11, 9, 10 and 7 is bc there is Ca right there next to it.

Question 20

Hemostasis-Extrinsic Pathway Overview

OVERVIEW: Invasive trauma to the oral tissues is followed by bleeding which can obscure the adjacent teeth and interfere with clinical treatment.

Within a few secs. the terminal arterioles ___ , reducing blood flow into the injured site.

Platelets ___ , to the exposed submucosa, become activated and agglutinate to form a platelet plug.

Answer 20

Hemostasis-Extrinsic Pathway Overview

OVERVIEW: Invasive trauma to the oral tissues is followed by bleeding which can obscure the adjacent teeth and interfere with clinical treatment.

Within a few secs. the terminal arterioles constrict, reducing blood flow into the injured site.

Platelets adhere, to the exposed submucosa, become activated and agglutinate to form a platelet plug.

Question 21

Initial Fibrin to interact with Platelet Plug

Within 30 secs following oral trauma, the ____ pathway is activated to generate ____ , which stimulates conversion of fibrinogen to fibrin.

A SOFT, ___ ___ CLOT is formed with the platelet plug to reduce or stop blood loss.

Continuous ____ formation is provided by the ____ PATHWAY and by ____ feedback from the THROMBIN.

Continues for a couple of minutes

Within ____ the clot becomes stable and bleeding stops.

Answer 21

Initial Fibrin to interact with Platelet Plug

Within 30 secs following oral trauma, the EXTRINSIC pathway is activated to generate THROMBIN, which stimulates conversion of fibrinogen to fibrin.

A SOFT, UNSTABLE FIBRIN CLOT is formed with the platelet plug to reduce or stop blood loss.

Continuous FIBRIN formation is provided by the INTRINSIC PATHWAY and by positive feedback from the THROMBIN.

Continues for a couple of minutes

Within mins the clot becomes stable and bleeding stops.

Question 22

Obj #9 Two Major Complexes in the Extrinsic Pathway

1st Complex- the discharge of ____ ____ from injured oral mucosa in the presence of ____ interacts with Factor ____ and it (7) becomes an____ serine protease VIIa.

2nd Complex (____ pathway) involves Factor ___ activation and a complex of cofactor __, ___, ___ ___ ___ and ____. The active enzyme ____ is formed

Answer 22

Obj #9 Two Major Complexes in the Extrinsic Pathway

1st Complex- the discharge of tissue thromboplastin from injured oral mucosa in the presence of Ca++ interacts with Factor VII and it (7) becomes an active serine protease VIIa.

2nd Complex (common pathway) involves Factor X activation and a complex of cofactor V, Prothrombin, Platelet factor 3 and Ca++. The active enzyme THROMBIN is formed

Question 23

The “Multitasker”Thrombin

Obj #10 Identify the primary action of thrombin that is essential for the development of a clot.

Answer: The enzyme, thrombin,___ soluble ___ to i____ polymerized fibrin.

Obj #11- Recognize 3 secondary actions of thrombin. which will satisfactorily occlude the injured microvasculature and stop bleeding. (fig 11-13)

Answer: Enhances activation of ____, of factor ___, and ___ ____

Thrombin Roles in Hemostasis

Stimulates conversion of Fibrinogen to Fibrin

Activates Factor Stabilizing Fibrin meshwork of Clot

Fibrin (Loose Meshwork) à Fibrin (___ meshwork) by Factor 13

Enhances activation of more prothrombin into thrombin thru + feedback

Enhances platelet aggregation

Thru + feedback aggregated platelets secrete PF3, which stim clotting cascade that results in thrombin activation

Factor 13 polymerizes the Clot and makes it a lot more stable so that it stays in place and doesn’t get washed away when you drink something

Prothrombin is very common in the circulatory system

Answer 23

The “Multitasker”Thrombin

Obj #10 Identify the primary action of thrombin that is essential for the development of a clot.

Answer: The enzyme, thrombin, cleaves soluble fibrinogen to insoluble polymerized fibrin.

Obj #11- Recognize 3 secondary actions of thrombin. which will satisfactorily occlude the injured microvasculature and stop bleeding. (fig 11-13)

Answer: Enhances activation of prothrombin, of factor XIII, and platelet aggregation.

Thrombin Roles in Hemostasis

Stimulates conversion of Fibrinogen to Fibrin

Activates Factor Stabilizing Fibrin meshwork of Clot

Fibrin (Loose Meshwork) à Fibrin (Stabilized meshwork) by Factor 13

Enhances activation of more prothrombin into thrombin thru + feedback

Enhances platelet aggregation

Thru + feedback aggregated platelets secrete PF3, which stim clotting cascade that results in thrombin activation

Factor 13 polymerizes the Clot and makes it a lot more stable so that it stays in place and doesn’t get washed away when you drink something

Prothrombin is very common in the circulatory system

Question 24

Obj #12 Intrinsic Pathway

Formation of thrombin by this pathway occurs after the extrinsic pathway has formed the ___ ___.

The Intrinsic pathway continues to form active coagulation factors until ___ ____

This pathway consists of a number of inactive serine proteases that must be activated in the presence of_____ .

In our blood stream we have both clotting factors and cofactors that assist in the formation of the serine protease

Answer 24

Obj #12 Intrinsic Pathway

Formation of thrombin by this pathway occurs after the extrinsic pathway has formed the initial fibrin.

The Intrinsic pathway continues to form active coagulation factors until bleeding stops.

This pathway consists of a number of inactive serine proteases that must be activated in the presence of cofactors.

In our blood stream we have both clotting factors and cofactors that assist in the formation of the serine protease

Question 25

Summary of the Intrinsic Pathway

Vessel Damage and Exposed Collagen

This leads to platelet aggregation

At the same time this activates Factor ____

You can use cotton to activate factor 12

12 activates the next factor… which activates next factor…which activates next factor…

Activation of ____

Formation of Fibrin Meshwork

___ vessel

Answer 25

Summary of the Intrinsic Pathway

Vessel Damage and Exposed Collagen

This leads to platelet aggregation

At the same time this activates Factor 12

You can use cotton to activate factor 12

12 activates the next factor… which activates next factor…which activates next factor…

Activation of Thrombin

Formation of Fibrin Meshwork

Seal vessel

Question 26

Obj # 13. Activation of Factor IX & VIII (8 and 9)

Factor IX is a ____ chain glycoprotein ___ ___ that must be activated.

It is____ ___ dependent and has about 12 gla residues for binding to ___ and then to PL, platelet phospholipid (____).

Factor VIII, Antihemophilic factor, is the___ ____ involved in this pathway.

It is very important in factor ___ activation.

It circulates as a series of ___ and is transported with___ ___ ___.

Its T1/2 is ___, 10 hours and much less with vWF deficiency.

Genes for these are located on the X csome

Women are carriers of these deficiencies and males have the disease

Hemophilia: decrease in 8

If see women with normal platelet count but has superficial bleeding, he suspects she has vWF deficiency not Hemophilia

Answer 26

Obj # 13. Activation of Factor IX & VIII

Factor IX is a single chain glycoprotein serine protease that must be activated.

It is Vitamin K dependent and has about 12 gla residues for binding to Calcium and then to PL, platelet phospholipid (PF3).

Factor VIII, Antihemophilic factor, is the largest cofactor involved in this pathway.

It is very important in factor X activation.

It circulates as a series of multimers and is transported with von Willebrand factor.

Its T1/2 is short, 10 hours and much less with vWF deficiency.

Genes for these are located on the X csome

Women are carriers of these deficiencies and males have the disease

Hemophilia: decrease in 8

If see women with normal platelet count but has superficial bleeding, he suspects she has vWF deficiency not Hemophilia

Question 27

Obj # 14 /Key Factor, X

Factor X is secreted from the____

It is Vit K dependent

A glycoprotein with 11 Gla residues.

It is secreted as an inactive ___ ____

Its half life is about___ hours and is relatively stable.

It plays a KEY ROLE in ____ activation to ____

It plays a KEY ROLE in the ___ pathway by activating factor ___ in the presence of the antihemophillic cofactor ___

Its at the intersection of the intrinsic and extrinsic pathways, where common pathway begins

Answer 27

Obj # 14 /Key Factor, X

Factor X is secreted from the liver

It is Vit K dependent

A glycoprotein with 11 Gla residues.

It is secreted as an inactive serine protease.

Its half life is about 70 hours and is relatively stable.

It plays a KEY ROLE in prothrombin activation to thrombin.

It plays a KEY ROLE in the intrinsic pathway by activating factor IX in the presence of the antihemophillic cofactor VIII.

Its at the intersection of the intrinsic and extrinsic pathways, where common pathway begins

Question 28

Factor 9 activates 10. They are bound to ___

10 activates ____ which is free to be released and cut fibrinogen to fibrin

Answer 28

Factor 9 activates 10. They are bound to Ca.

10 activates prothrombin which is free to be released and cut fibrinogen to fibrin

Question 29

Obj #15 Stabilized Fibrin/Blood Clot

Within the first 10-15 mins, new blood clots are relatively ____ and the fibrin meshwork is loose with ___ cross links (fig 11-14).

During this time unstable fibrin can be dislodged, especially in the oral cavity with chewing.

Factor___ is a large plasma zymogen that is activated by ____

An alpha chain is exposed which binds to ____ and converts fibrin into several _____ complexes.

This final step in the polymerization of fibrin is important for ___ ___ and ___ ____

13 is___ ____ _____ bc it doesn’t need PF3 to work, it just needs Ca

If you don’t have 13, the clot never becomes stable and you wont have good wound repair

Answer 29

Obj #15 Stabilized Fibrin/Blood Clot

Within the first 10-15 mins, new blood clots are relatively unstable and the fibrin meshwork is loose with few cross links (fig 11-14).

During this time unstable fibrin can be dislodged, especially in the oral cavity with chewing.

Factor XIII is a large plasma zymogen that is activated by thrombin.

An alpha chain is exposed which binds to Ca++ and converts fibrin into several crosslinked complexes.

This final step in the polymerization of fibrin is important for wound healing, and tissue repair.

13 is not Vit K dependent bc it doesn’t need PF3 to work, it just needs Ca

If you don’t have 13, the clot never becomes stable and you wont have good wound repair

Question 30

16-A Identify the steps involved in fibrinolysis and the enzymatic regulation of this system.

Obj #16 Fibrinolysis

(Fig. 19.1 Hathaway & Goodnight); (Human Physiol pgs 410-411)

___ produces plasminogen

Plasmin is an enzyme that comes from ___ ____

tPA comes from the___ ___ of the ____

Breakdown of fibrin to complete wound healing and repair

Have to get rid of the blood clot and get bridging of wound with epithelial tissue

Answer 30

16-A Identify the steps involved in fibrinolysis and the enzymatic regulation of this system.

Obj #16 Fibrinolysis

(Fig. 19.1 Hathaway & Goodnight); (Human Physiol pgs 410-411)

Liver produces plasminogen

Plasmin is an enzyme that comes from plasminogen breakdown

tPA comes from the endothelial cells of the vasculature

Breakdown of fibrin to complete wound healing and repair

Have to get rid of the blood clot and get bridging of wound with epithelial tissue

Question 31

Ruptured endothelium releases____

tPA gets in the ___ ___ So does plasminogen. And cuts it to ____

That starts destroying the ___ ___ but it can also leave. It’s a very active enzyme.

Answer 31

Ruptured endothelium releases tPA

tPA gets in the blood clot. So does plasminogen. And cuts it to plasmin.

That starts destroying the blood clot but it can also leave. It’s a very active enzyme.

Question 32

Plasminogen binds to the blood clot.

tPA binds the blood clot and activates plasminogen to plasmin.

Plasmin cuts the fibrin down into small fragments.

Theres an ____ in case this escapes out into the plasma

Answer 32

Plasminogen binds to the blood clot.

tPA binds the blood clot and activates plasminogen to plasmin.

Plasmin cuts the fibrin down into small fragments.

Theres an antiplasmin in case this escapes out into the plasma