Chapter 9 - Venous pathophysiology

Question 1

Endothelial surface maintenance mechanisms

Answer 1

1) thrombomodulin production –> activate protein C 2) heparan sulfate and dermatin sulfate expression –> accelerate antithrombin and heparin cofactor II activity 3) expression of tissue factor pathway inhibitor 4) production of TPA and UPA 5) production of NO and prostacyclin –> inhibit adheion of leukocytes

Question 2

Difference between venous and arterial endothelium

Answer 2

1) venous has vWF expression 2) venous has less tpa

Question 3

Vein and artery elastin and collagen content

Answer 3

Vein is higher in elastin and lower in collagen after DVT collagen increases

Question 4

Protein C, Coag and fibrinolytic pathway flow diagram

Answer 4

FIGURE 9.1

Question 5

Hageman factor

Answer 5

Factor XII

Question 6

Activation of Factor XII

Answer 6

Complex to prekallikrein and high-molecular-weight kininogen (HMWK) on negatively charged surface to form Factor XIIa

Question 7

Function of Factor XIIa

Answer 7

Activates factor XI to XIa

Question 8

Thrombin is

Answer 8

Factor II

Question 9

Action of thrombin

Answer 9

1) Cleavage of fibrinogen into fibrinopeptide A and B cross links and stabilizes thrombus and platelet plug 2) Activates factor XIII to XIIIa –> catalyze cross linking of fibrin, fibronectin, alpha2-antitrypsin –> incorporates into thrombus

Question 10

Function of Factor XIIIa

Answer 10

Activate factor V and VIII –> increase thrombin production

Question 11

Activation of platelets two pathways

Answer 11

Disulfide isomerase –> TF de-encryption –> factor VIIa generation –> activate platelet subendothelial collage –> bind glycoprotein VI and vWF –> platelet capture and activation

Question 12

Platelet effects

Answer 12

1) plt releases receptors for Coag Factor Va and VIIIa 2) elaboration of arachidonic acid metabolite (TXA2) –> promote plt aggregation and vasoconstriction 3) plt shape change exposes negative procoagulant phospholipids 4) release microparticles with TF and other procoagulants

Question 13

Effects of antithrombin

Answer 13

1) inhibit thrombin prevents removal of FPA and FPB from fibrinogen –> limit fibrin formation 2) thrombin unavailable for activation of Factors V and VIII –> slows coag cascade 3) thrombin-mediated plt activation and aggregation inhibited

Question 14

Activation of protein C

Answer 14

1) Thrombin on endothelium binds thrombomodulin and endothelial protein C receptor 2) thrombin-thrombomodulin complex –> inhibits thrombin and activates protein C to activated protein C (APC) 3) APC in presence of cofactor protein S inactivates factor Va and VIIIa 4) Xase and prothrombinase activity reduced

Question 15

Function of TFPI (tissue factor pathway inhibitor)

Answer 15

1) binds TF VIIa complex 2) inhibit activation of factor X to Xa

Question 16

Natural anticoagulants

Answer 16

1) antithrombin 2) activated protein C 3) TFPI 4) heparin cofactor II

Question 17

Plasmin what is it

Answer 17

1) serine protease 2) generated by proteolytic cleavage of proenzyme plasminogen 3) substrate = fibrin, fibrinogen, other coag factors 4) interferes with vWF-mediated plt adhesion by proteolysis of GPIb

Question 18

Activation of plasminogen

Answer 18

1) fibrin-bound tpa 2) uPA (less affinity for fibrin) 3) contact activation system: activated forms of factor XII, kallikrein, factor XI 4) activated protein C –> inactivate PAI-1

Question 19

D-dimer origin

Answer 19

Degradation of fibrin by plasmin –> fragment E and two fragment D two fragment D covalent link = D-dimer

Question 20

PAI-1 effect

Answer 20

Primary inhibitor of plasminogen activators secreted in active form from liver and endothelial cells stabilized by binding vitronectin

Question 21

PAI-1 source

Answer 21

Alpha granules of quiescent platelets

Question 22

PAI-1 levels increase in these conditions

Answer 22

1) hyperlipidemia 2) factor V leiden

Question 23

Contents of microparticles

Answer 23

From platelets contain transcription factors and phosphatidylserine

Question 24

Galectin 3 key points

Answer 24

1) upregulated in MPs from DVT patients 2) member of lectin family associated with integrin-mediated cell adhesion