Secondary hemostasis

Question 1

Secondary hemostasis, or the coagulation cascade, can be remembered as a series of amplifying _____ reactions, happening on a ____ surface, culminating in ____ generation.

Answer 1

amplifying serine protease reactions

on a phospholipid surface (often platelet surface)

culminating in thrombin generation

Question 2

What are three majors role of how thrombin promotes coagulation?

Answer 2

1. cleaves soluble plasma protein (fibrinogen) into insoluble coagulum (fibrin)
2. directs irreversible platelet aggregation
3. activates factor XIII->factor XIIIa, which forms covalent crosslinks between fibrin molecules

Question 3

Most of the coagulation factors are synthesized by?

Answer 3

Hepatocytes

Question 4

Blood coagulation cascade may result from intrinsic or extrinsic pathway. What may cause either?

Answer 4

Intrinsic - damaged surface

Extrinsic - trauma

Question 5

Fibrin monomers (created through action of thrombin on fibrinogen) polymerize to form _____. What does this do to blood?

Answer 5

fibrin fibrils, which form a strong gel and immobilize blood.

Question 6

What happens in the intrinsic pathway of blood coagulation?

Answer 6

Tissue injury results in the exposure of blood to negative charged surfaces (extracellular matrix glycosaminoglycans, NET made of DNA). These surfaces bind and activate

factor XII (contact system), activating factor XI to XIa.

Question 7

What happens in the extrinsic pathway of blood coagulation?

Answer 7

Exposure of TF (tissue factor), an intrinsic membrane glycoprotein in endtohelial cells, fibroblasts and monocytes normally not visible to coagulation system.

Question 8

I skipped the coagulation biochem pathways. Please read

Answer 8

Please

Question 9

All coagulation pathways work through generation of ___

Answer 9

Thrombin

Question 10

Tell me about thrombin receptors

Answer 10

Protease activated receptor (PAR): GPCR activated by thrombin cleavagee

Proteolytic cleavage of the receptor created a new N-terminus, and this was ligand for receptor

Question 11

Thrombin activates which factors, as well as activates platelets and endothelial cells through PAR)?

It also cleaves __

Answer 11

Thrombin activates factors V, VIII, XI

cleaves fibrinogen -> fibrin

activates factor XIII

platelet activator

Question 12

When bound to thrombomodulin, thrombin stops activating___, instead activates

Answer 12

stops acting towards fibrinogen, instead increases activity
Protein C, anticoagulant
(becomes APC: active protein C)

Question 13

Coagulation remains localized due to autolysis of coagulation factors, dilution if they go far from the local site, or inhibition formed by inhibitor proteins encoded by what gene?

Answer 13

SERPINC1

encodes antithrombin, a serpin which inhibits thrombin and serine proteases in cascade XIIa, XIa, IXa, Xa..

These irreversibly bind to protease active site.

Question 14

AT functionality is enhanced 1000-fold by presence of

Answer 14

negatively charged glycosaminoglycans like heparan sulfate.

Question 15

What does active Protein C do, and how is it made?

Answer 15

It’s made when thrombin binds thrombomodulin, which is found in surface of endothelial cells.

In conjunction with protein S, cofactor, APC cleaves Factor Va or VIIIa into active fragments, dampening generation of thrombin

Question 16

During healing and repair, dissolution of the fibrin thrombus must occur by cleaving the fibrin. What enzyme cleaves the fibrin, and what is that enzyme’s precursor?

Answer 16

Plasmin, a serine protease. Is formed by precursor plasminogen.

Question 17

How is plasminogen activated?

Answer 17

Two main activators: TPA or tissue plasminogen activator, and urokinase

Question 18

How can you measure secondary hemostasis in the lab?

Answer 18

active plasma, measure time to clot (endpoint is initiation of fibrin meshwork, not firm, crosslinked clot)