Secondary Hemostasis

Question 1

Secondary Hemostasis timing and factors

Answer 1

-occurring at same time as primary hemostasis
-uses coagulation factors and cofactors called serine proteases that are either circulating or released from platelets

Question 2

Goal of hemostasis

Answer 2

-create an insoluble, fibrin clot that stabilizes and replaces the platelet plug

Question 3

Anti-coagulation role in secondary hemostasis

Answer 3

-keep the fibrin clot concise and in the area of endothelial injury without excessive formation
-also resorbs the fibrin clot as the endothelium regrows/repairs

Question 4

Secondary hemostatic disorder

Answer 4

-delayed hemorrhage (several hours or longer)

Question 5

Coagulation factors

Answer 5

-Fibrinogen (Factor I)- concentrate on surface to give structure for fibrin
-Tissue Factor (TF; Factor III)- triggers secondary hemostasis
-Ca2+ (Factor IV)
-Prothrombin (Factor II) – modulates procoagulation
-Factors VII, IX, X,XI XII

Question 6

Coagulation cofactors

Answer 6

**from platelets, assist other factors
-Factor V
-Factor VIII

Question 7

Intrinsic pathway

Answer 7

-includes everything except TF and VIIa

Question 8

Extrinsic pathway

Answer 8

-includes common pathway and TF and VIIa
-begins when TF (released from damages tissues) and VIIa combine

Question 9

Common pathway

Answer 9

-Factor X and its following factors
-Prothrombin becomes thrombin which recruits fibrinogen to make fibrin
>also activates many different areas

Question 10

Prolonged PTT vs.normal PT

Answer 10

-Normal PT indicates that common pathway is not an issue
-narrows it down to intrinsic pathway

Question 11

Three stages of secondary hemostasis

Answer 11

**all stages are overlapping, not sequential
1.Initiation
2. Amplification
3. Propagation

Question 12

Initiation of secondary hemostasis

Answer 12

-mainly extrinsic pathway
-start of thrombin production

Question 13

Amplification of secondary hemostasis

Answer 13

-increasing levels of thrombin production

Question 14

Propagation of secondary hemostasis

Answer 14

-mainly intrinsic pathway
-maximized thrombin production

Question 15

Pathway Steps

Answer 15

-TF released and attaches to cell surface
-TF combines to VII which forms the tenase complex?
-Activates factor X
-Factor X combines with Factor V
-Results in activation of Prothrombin (Factor II) to Thrombin (factor IIa)
>leads to activation of fibrinogen (factor I) to fibrin (factor Ia)
>also leads to intrinsic pathway activation

Question 16

Prothrombinase complex

Answer 16

-Includes Xa and Va which results in prothrombin to thrombin activation

Question 17

Factor XII

Answer 17

-physically cleaved by collagen fibres
-activates Factor XI and intrinsic pathway

Question 18

Factor II vs. Factor XII activation of intrinsic

Answer 18

-factor II is better at activating the intrinsic pathway than Factor XII

Question 19

Making factors sticky

Answer 19

1.Platelets have Ca 2+ on surface
2.Factors II, IX, VII, X (1972) gain negative charge
3.Postive and negative charges attract= sticky

Question 20

Gamma-glutamyl carboxylase

Answer 20

-adds negative charges to help factors II, VII, IX, and X stick to the positively charged platelets

Question 21

Why are platelets positively charged?

Answer 21

-because they are covered in Ca2+

Question 22

Factor XIII

Answer 22

-helps to crosslink fibrin strands into rafts
-activated by factor IIa (thrombin)

Question 23

Inhibitors of coagulation

Answer 23

-factors that prevent clotting

Question 24

Antithrombin

Answer 24

-inactivates thrombin
-can be measured in the plasma

Question 25

What enhances antithrombin?

Answer 25

-enhanced by heparan sulfate (produced by endothelial cells and injections of heparin)
Nephrotic syndrome
-antithrombin loss
-results in hypercoagulation; inappropriate thrombus formation and death

Question 26

Thrombomodulin

Answer 26

-binds thrombin and inhibits its function
-activates protein C and cofactor protein S which inactivates cofactors Va and VIIIa

Question 27

Tissue factor pathway inhibitor

Answer 27

-inhibits tissue factor
-how endothelial cells and platelets release factors that work to finely tune a precise clot only in the area of damaged endothelium

Question 28

Fibrinolysis

Answer 28

-Tissue plasminogen activator (tPA) is released from damaged endothelial cells and converts circulating plasminogen to plasmin
>Plasmin has high affinity for fibrin and cleaves it into fibrin degradation products which can me measured

Question 29

Clinical manifestations of defects in secondary hemostasis

Answer 29

1.Ecchymoses
2. Internal and external hemorrhage

Question 30

Tests for secondary hemostasis disorders

Answer 30

-PT and PTT tests
-FDP measurement- assesses degree of fibrinolysis (how much coagulation is occurring?)
-Antithrombin measurement- excessive loss leading to hypercoagulation

Question 31

Hemophilia A

Answer 31

-deficiency of factor VIII
-detected in PTT

Question 32

Hemophilia B

Answer 32

-deficiency in factor IX
-detected in PTT

Question 33

Vitamin K antagonist toxin

Answer 33

-detects via prolongation in both PT and PTT

Question 34

Hepatic failure

Answer 34

-insufficient coagulation factor synthesis
-can result in prolongation in both PT and PTT

Question 35

DIC

Answer 35

-consumptive coagulopathy
-a number of potential causes
-results in both hypocoagulation and hypercoagulation, thrombocytopenia, induced thrombopathia, erythrocyte fragmentation