Secondary Hemostasis (Exam 2)

If there is a small "a" next to a coagulation factor, it means it is ______.

activated

Coagulation factors circulate as inactive ______ until the need for repair arises.

zymogens

Coagulation factor activation occurs when the single peptide chain gets ______ by proteases.

cleaved

What are the three groups of coagulation factors?

- Vitamin K Dependent

- Contact Factor

- vWF: Factor VIII

Factor I

Fibrinogen

Factor II

Prothrombin

(IIa is thrombin)

Factor III, tissue factor

Tissue Thromboplastin

Factor IV

Calcium ions

Factor V

Proaccelerin, Labile Factor

Factor VII

Proconvertin, Stabile Factor

Factor VIII:C

Anti-Hemophilic Factor (AHF)

Factor VIII R:Ag Factor VIII vWF

Von Willebrand Factor

Factor IX

Christmas Factor, Anti-Hemophilic Factor B

Factor X

Stuart-Prower Factor

Factor XI

Plasma Thromboplastin Antecedent (PTA)

Factor XII

Hageman Factor

Factor XIII

Fibrin Stabilizing Factor

Prekallikrein (PK)

Fletcher Factor

HMWK (High Molecular Weight Kininogen)

Fitzgerald Factor

What factors make up the Vitamin K Dependent group?

- Factor II (prothrombin)

- Factor VII

- Factor IX

- Factor X

- Proteins C, S, and Z

These factors need vitamin K for their ______.

activation

The Vitamin K Dependent group are also called the ______ group.

Prothrombin

The Contact Factor group is involved in the contact activation step of the ______ pathway of the coagulation cascade.

intrinsic

What are the Contact Factor group factors?

- Factor XII

- Factor XI

- HMWK

- PK

Factor XII and PK are ______.

proteases

HMWK is a ______.

cofactor

The Contact Factor group bind to ______ surfaces

negatively charged

Factor VIII: von Willebrand Factor group

- Factor VIII

- vWF

vWF is a glycoprotein composed of multiple subunits synthesized by ______ and ______.

megakaryocytes, vascular endothelial cells

Factor VIII is synthesized by the ______, driven by the X chromosome.

liver

vWF and Factor VIII are ______ in circulation.

covalently bound

What are the cofactors?

- Factor V (Factor Xa)

- Factor VIII (Factor IXa)

- HMWK (Factor XIIIa and XIa)

- Protein S (activated Protein C)

- Tissue Factor (Factor VIIa)

Interaction of protease with cofactor significantly increases ______ activity.

enzyme

______ is the only coagulation protein that does not become an activated enzyme.

Fibrinogen

What are the serine proteases?

- Thrombin

- Factor VIIa

- Factor IXa

- Factor Xa

- Factor XIa

- Factor XIIa

______ is a trans-glutaminase.

Factor XIIIa

Coagulation Cascade

The intrinsic pathway molecules are all found in ______.

plasma

What are the factors involved in the intrinsic pathway?

- Factor XII

- Factor XI

- Factor PK

- Factor HK

These factors are activated when exposed to ______ surfaces.

negatively charged

Lack of these factors does not cause ______ problems.

bleeding

These factors are more active in ______, ______ and ______ activation.

fibrinolysis, inflammation, complement

Intrinsic Pathway steps

1. Factor XII --> XIIa

2. XIIa activates prekallikrein to kallikrein

3. XIIa converts XI --> XIa (requires HMWK)

4. XIa converts IX --> IXa (with Ca2+)

5. IXa + VIIIa + Ca2+ binds to platelets to activate X --> Xa

The extrinsic pathway requires ______ which is not normally found in blood or on cells exposed to blood.

Tissue Factor

Tissue Factor is constitutively expressed on ______ cells.

nonvascular

Monocytes and endothelial cells are induced to express Tissue Factor by ...

- Endotoxin

- C5a

- IL-1

- TNF

Tissue Factor is the cellular receptor and cofactor for ______ and ______.

Factor VII, Factor VIIa

Extrinsic Pathway steps

1. Factor VIIa + TF cleaves X --> Xa

2. Factor VIIa + TF can also cleave IX --> IXa

Common Pathway

Xa + Factor Va + Ca2+ + phospholipid = Prothrombin (Factor II) --> Thrombin (Factor IIa)

As a procoagulant, thrombin induces platelet ______ and ______.

activation, aggregation

Thrombin activates PLT aggregation through promoting the secretion of ______ and ______, both of which are procoagulants.

serotonin, TXA2

As a procoagulant, thrombin activates cofactor ______ to ______.

VIII, VIIIa

As a procoagulant, thrombin converts fibrinogen to ______.

fibrin

Activation of fibrinogen by thrombin involves the removal of the ______ subunits on fibrinogen.

A and B

Fibrin

Thrombin stabilizes the fibrin monomer by activating factor ______.

XIII

Activated Factor XIII arranges the fibrin polymer in a lattice formation so that the ______ line up to form a dimer, making the clot stable.

D fragments

Once, formed, thrombin can go back into the cascade and further activate which factors?

- Factor VIII

- Factor V

- Factor XI

- Factor XIII

Common pathway

As a procoagulant, thrombin converts prothrombin to ______ through autocatalysis.

thrombin

As an anticoagulant/fibrinolytic component, thrombin binds with AT III to inhibit ______.

serine proteases

As an anticoagulant/fibrinolytic component, thrombin promotes endothelial release of ______.

t-PA

As an anticoagulant/fibrinolytic component, thrombin binds to thrombomodulin to activate ______.

protein C

The main physiologic inhibitor of thrombin is ______.

Antithrombin III (AT III)

AT III also inhibits ...

- Factor Xa

- Factor IXa

- Factor XIa

- Factor XIIa

- Protein C

- Prekallikrein

Neutrophils and monocytes respond to ______ and undergo chemotaxis.

thrombin

These cells mediate ______ release, which stimulate the proliferation of fibroblasts, smooth muscle cells and endothelial cells.

Platelet-Derived Growth Factor (PDGF)