Hemostasis 2 (Thomas)

Question 1

What is antithrombin (AT/ATIII)?

Answer 1

A low molecular weight protein produced by hepatocytes.

• It is the most important endogenous anticoagulant.
• Inhibits thrombin
• Regulates coagulation cascade
• Prevent blood clots from forming in blood vessels, reducing the risk of thrombosis

Question 2

What enzymes does antithrombin inhibit?

Answer 2

Most coagulation enzymes:
IIa, VIIa, IXa, Xa, XIa, and XIIa
2a, 7a, 9a, 10a, 11a, 12a

Question 3

What is the primary function of antithrombin?

Answer 3

Keeps coagulation in check and prevents excessive or inappropriate thrombus formation.

Question 4

What is heparin, and how is it used?

Answer 4

Heparin is a therapeutic product used clinically as an anticoagulant.

Question 5

Where does heparan sulfate come from?

Answer 5

It is produced by endothelial cells.

Question 6

How does heparan sulfate enhance antithrombin activity?

Answer 6

It exposes the ATIII binding site, causing a conformational change that permits ATIII to bind coagulation enzymes and form inactive complexes.

ATIII - antithrombin 3

Question 7

What is the purpose of tertiary hemostasis (fibrinolysis)?

Answer 7

• Breaks down fibrin clots
• Promotes revascularization
• Restores blood flow to tissues
• Keeps thrombus formation in check

Question 8

What happens to fibrin during fibrinolysis?

Answer 8

Fibrin is broken down into fibrin degradation products (FDPs) by plasmin.

Question 9

How is plasmin formed?

Answer 9

Plasmin is the activated form of plasminogen, requiring tissue plasminogen activator (tPA) or factor XIIa/kallikrein.

Question 10

How is free plasmin regulated?

Answer 10

It is inhibited by antiplasmin.

Question 11

What is the role of tissue plasminogen activator (tPA)?

Answer 11

Produced by endothelial cells, it activates plasminogen to plasmin.

Question 12

What is the role of plasminogen activator inhibitor (PAI)?

Answer 12

It inhibits tPA, preventing plasmin formation.

Question 13

How do fibrin degradation products (FDPs) impair coagulation directly?

Answer 13

By competing with fibrinogen for thrombin.

Question 14

How do FDPs impair coagulation indirectly?

Answer 14

By binding to platelet fibrinogen receptors.

Question 15

What test measures FDPs and D-dimers?

Answer 15

Immunoassays.

Question 16

Why can’t FDPs alone confirm fibrinolysis?

Answer 16

Because FDPs can come from fibrin, fibrinogen, or cross-linked fibrin.

FDP = fibrin degredation products

Question 17

What does the presence of D-dimers confirm?

Answer 17

That cross-linked fibrin (a true clot) was formed and broken down during fibrinolysis.

Question 18

What is a limitation of FDP/D-dimer testing in animals?

Answer 18

Most assays are designed for humans and may not cross-react with all veterinary species.

Question 19

Step 1 of fibrinolysis: How does plasminogen become activated?

Answer 19

Mainly by tissue plasminogen activator (tPA), but also by factor XIIa/kallikrein.

Question 20

Step 2 of fibrinolysis: What does plasmin do?

Answer 20

Breaks down fibrin into fibrin degradation products (FDPs).

Question 21

Step 3 of fibrinolysis: How do FDPs impair coagulation?

Answer 21

They compete with fibrinogen for thrombin and bind to platelet fibrinogen receptors.

Question 22

Step 4 of fibrinolysis: How is the process regulated?

Answer 22

• PAI inhibits tPA
• Antiplasmin inhibits free plasmin

Question 23

Where is tissue plasminogen activator (tPA) produced?

Answer 23

By endothelial cells.

Question 24

What is the role of tissue plasminogen activator?

Answer 24

Converts plasminogen into active plasmin, which degrades cross-linked fibrin.

Question 25

How does latex agglutination test for FDPs/D-dimers?

Answer 25

Latex beads are added to the sample; if FDPs or D-dimers are present, visible agglutination occurs.

Question 26

How does turbidimetry test for FDPs/D-dimers?

Answer 26

Measures light scatter through the sample; turbidity correlates with FDP/D-dimer concentration.

Question 27

What clinical outcome results from defects in tertiary hemostasis?

Answer 27

Thrombosis (inappropriate clot or platelet formation).

Question 28

What laboratory findings suggest defects in tertiary hemostasis?

Answer 28

Increased platelet activity and coagulation, with decreased fibrinolysis and anticoagulant activity.

Question 29

What disease factors can cause tertiary hemostasis defects?

Answer 29

Vessel damage or diseases affecting endothelial function.

Question 30

In health, what is the overall function of resting endothelial cells?

Answer 30

They are antithrombotic, inhibiting clot formation through antiplatelet, anticoagulant, and fibrinolytic mechanisms.

Question 31

What antiplatelet activities do resting endothelial cells have?

Answer 31

Secrete NO and PGI₂ (prostacyclin): inhibit platelets + cause vasodilation; secrete enzyme that inhibits ADP.

Question 32

What anticoagulant activities do resting endothelial cells have?

Answer 32

* Heparan sulfate on surface acts as cofactor for ATIII * Thrombomodulin binds thrombin → activates protein C * Tissue factor pathway inhibitor (TFPI). * Secrete nitric oxide (NO) and PGI2

Question 33

What fibrinolytic activity do resting endothelial cells have?

Answer 33

Synthesize tissue plasminogen activator (tPA), promoting plasmin formation and fibrin breakdown.

Question 34

What are the major prothrombotic activities of activated endothelial cells?

Answer 34

Promote platelet plug formation, promote coagulation, and inhibit fibrinolysis.

Question 35

How do activated endothelial cells promote platelet plug formation?

Answer 35

* Synthesize von Willebrand factor (vWF) * Release platelet activators * Downregulate platelet inhibitors * Upregulate adhesion molecules for platelets

Question 36

How do activated endothelial cells promote coagulation?

Answer 36

Express tissue factor (TF); downregulate heparan sulfate, thrombomodulin, and TF pathway inhibitors.

Question 37

How do activated endothelial cells inhibit fibrinolysis?

Answer 37

They secrete plasminogen activator inhibitor (PAI), which binds and inhibits tPA.

Question 38

IC: What cells or factors are directly inhibited by ATIII in health? a. FVa --> not an enzyme b. FXa c. Platelets d. Tissue factor

Answer 38

b. FXa

Question 39

IC: Where does ATIII come from? a. Lymphocytes b. Hepatocytes c. Bone marrow d. Renal tubular epithelial cells

Answer 39

b. Hepatocytes

Question 40

IC: What is the connection between endothelial cells and ATIII? a. Endothelial cells produce ATIII b. No connection c. ATIII blocks TF on surface of endothelial cells d. Endothelial cells express heparan sulfate, allowing ATIII to bind coagulation factors

Answer 40

d. Endothelial cells express heparan sulfate, allowing ATIII to bind coagulation factors

Question 41

IC: what is an antithrombotic property of endothelial cells? a. vWF secretion b. Surface expression of heparan sulfate c. Tissue factor expression when activated d. Plasminogen activator inhibitor secretion

Answer 41

b. Surface expression of heparan sulfate

Question 42

IC: what is a prothrombotic property of endothelial cells? a. vWF secretion b. Expression of surface thrombomodulin c. Tissue plasminogen activator secretion d. Secretion of platelet inhibitors (e.g. NO, PI2)

Answer 42

a. vWF secretion

Question 43

What factors does Protein C degrade?

Answer 43

* V (5) * VIII (8)

Question 44

What does Thrombomodulin do?

Answer 44

Binds thrombin (II) & activates Protein C