Overview of Hemostasis

Primary v Secondary hemostasis, fibrinolysis, Coagulation Factors, Functional Classification of Factors, and Summary of Coagulation Factors

Give a 3 step overview of Primary Hemostasis

1) Vasoconstriction, where blood vessels constrict to reduce blood flow

2) Platelet adhesion, when platelets stick to exposed collagen at the injury site

3) Platelet aggregation, leading to the formation of primary hemostatic plug at injury site

Give a 2 step overview of Secondary Hemostasis

1) Interaction of coag factors to produce fibrin (secondary hemostatic plug)

2) Fibrin stabilization by factor XIII

Give a 3 step overview of Fibrinolysis

1) Release of tissue plasminogen activator

2) Conversion of plasminogen to plasmin

3) Conversion of fibrin-to-fibrin degradation products

Provide the:

1) Name

2) Pathway(s)

3) Inherited Deficiencies

4) Comments

For Coagulation Factor I

Fibrinogen

I, E, and C pathways

Rare

Converted to fibrin by thrombin

Provide the:

1) Name

2) Pathway(s)

3) Inherited Deficiencies

4) Comments

For Coagulation Factor II

Prothrombin

I, E, and C pathways

Rare

It is a precursor to thrombin

Provide the:

1) Name

2) Pathway(s)

3) Inherited Deficiencies

4) Comments

For Coagulation Factor III

Tissue Factor (TF)

E pathway ONLY

N/A

It is a phospholipid released from the injured vessel wall. Not normally in blood.

Provide the:

1) Name

2) Pathway(s)

3) Inherited Deficiencies

4) Comments

For Coagulation Factor IV

Ca²⁺

I, E, and C pathways

N/A

It is bound by anticoagulant sodium citrate. In assays using citrated plasma, must be supplied by reagents.

Provide the:

1) Name

2) Pathway(s)

3) Inherited Deficiencies

4) Comments

For Coagulation Factor V

Labile Factor (Proaccelerin)

I, E, and C pathways

Rare

Deteriorates rapidly

Provide the:

1) Name

2) Pathway(s)

3) Inherited Deficiencies

4) Comments

For Coagulation Factor VII

Stable Factor (Proconvertin)

E pathway ONLY

Rare

Provide the:

1) Name

2) Pathway(s)

3) Inherited Deficiencies

4) Comments

For Coagulation Factor VIII

Antihemophilic Factor

I pathway ONLY

Common (Hemophilia A)

It circulates in association with VWF. VWF stabilizes VIII, prolonging half-life. VII:C = coagulant portion. Extremely liable.

Provide the:

1) Name

2) Pathway(s)

3) Inherited Deficiencies

4) Comments

For Coagulation Factor IX

Christmas Factor (plasma thromboplastin component)

I pathway ONLY

Common (Hemophilia B)

Provide the:

1) Name

2) Pathway(s)

3) Inherited Deficiencies

4) Comments

For Coagulation Factor X

Stuart Factor

I, E, and C pathways

Rare

Provide the:

1) Name

2) Pathway(s)

3) Inherited Deficiencies

4) Comments

For Coagulation Factor XI

Plasma thromboplastin antecedent

I pathway ONLY

Rare (Hemophilia C); May or may not cause bleeding

Provide the:

1) Name

2) Pathway(s)

3) Inherited Deficiencies

4) Comments

For Coagulation Factor XII

Hageman Factor (Contact factor)

I pathway ONLY

No bleeding

Glass activation factor, not part of in vivo coagulation (used in experiments, cannot be used in body)

Provide the:

1) Name

2) Pathway(s)

3) Inherited Deficiencies

4) Comments

For Coagulation Factor XIII

Fibrin stabilizing factor

I, E, and C pathways

Rare; poor wound healing

Stabilizes fibrin clot

Provide the:

1) Name

2) Pathway(s)

3) Inherited Deficiencies

4) Comments

For Coagulation Factor HMWK

High Molecular Weight Kininogen (Fitzgerald Factor)

I pathways ONLY

Rare; No bleeding

Not part of in vivo coagulation

Provide the:

1) Name

2) Pathway(s)

3) Inherited Deficiencies

4) Comments

For Coagulation Factor PK

Prekallikrein (Fletcher Factor)

I pathway ONLY

No bleeding

Not part of in vivo coagulation

What is a substrate?

A substance changed by an enzyme

Which coagulation factor is considered a substrate?

Fibrinogen

What is a cofactor?

A protein that accelerates enzymatic reactions, but it has no enzymatic activity of its own

Which coagulation factors are considered cofactors?

V is a cofactor for Xa

VIII is a cofactor for IXa

What is an enzyme?

A protein that catalyzes a change in specific substrate. It is secreted in inactive form (proenzyme, zymogen), and must be activated to function.

What coagulation factors are considered enzymes?

(2 categories - (SP)T)

Serine Proteases: Thrombin (IIa), VIIa, IXa, Xa, XIa, XIIa, Prekallikrein

Transglutaminase: XIIIa

Name the factors of the Contact Group and why?

Factors: PK, HMWK, XII, and XI

Why: They are involved in the initiation of the intrinsic pathway

Name the factors of the Prothrombin Group and why?

Factors: II, VII, IX, X

Why: These are Vitamin K- dependent factors, requiring Vitamin K for synthesis

Name the factors of the Fibrinogen Group and why?

Factors: I, V, VIII, XIII

Why: These factors are acted on by thrombin. Factors V, VIII, and XIII are activated and Factor I is converted to Fibrin.

Draw the In Vitro Coagulation Cascade. Include factors, cofactors, and enzymes used in the Intrinsic, Extrinsic, and Common pathways.

Intrin Factors: HMWK, PK, XII, XI, IX, and VIII

Extrin Factors: TF and VII

Common Factors: X, V, II, I

Name the factors of the Extrinsic tenase complex and which factor it acts on?

VIIa/TF

Acts on Factor X

Name the factors of the Intrinsic tenase complex and which factor it acts on?

IXa/VIIIa

Acts on Factor X

Name the factors of the Prothrombinase complex and which factor it acts on?

Xa/Va

Acts on Prothrombin

Name the factors of the Factor VIII complex? Which is the Procoagulant and which is the Carrier protein?

VIII:C & von Willebrand Factor (VWF)

VIII:C = procoagulant; VWF = carrier protein

Which factors are produced in the liver?

All of them

Which Coag Factors are affected by anticoagulant therapy (Coumadin aka Warfarin)? Why?

II, VII, IX, and X

Coumadin prevents clotting by inhibiting Vitamin K dependent factors

Which factors are consumed during clotting? Why?

I, II, V, VIII, XIII because they are not present in serum

Which factors are considered Labile factors?

V & VIII