3) Secondary hemostasis

Question 1

Intrinsic pathway

Answer 1

Question 2

Extrinsic pathway

Answer 2

Question 3

Common pathway

Answer 3

Question 4

In vitro intrinsic pathway

Answer 4

Question 5

the end product of secondary hemostasis

Answer 5

fibrin clot

Question 6

biochemical change resulting in activated coag factors

Answer 6

cleavage of peptide fragments

Question 7

required for the local concentration of trace plasma coag factors

examples

Answer 7

surface mediated interactions

in vivo: collagen, phospholipid vesicles (PF3)
in vitro: glass, ellagic acid, kaolin

Question 8

a small amount of enzyme formed initially leads to a relatively enormous quantity of enzyme

Answer 8

biological amplification system

Question 9

end stage enzyme of hemostasis

Answer 9

thrombin

Question 10

3 parts of fibrin clot formation

Answer 10

extrinsic pathway
intrinsic pathway
common pathway

Question 11

the ——- pathway relies on TF, which is limited, so it requires the ———- pathway for sustained coagulation to proceed

Answer 11

extrinsic
intrinsic

Question 12

TF is the limiting factor for…

Answer 12

extrinsic pathway

Question 13

intrinsic and extrinsic pathways converge by their action on…

Answer 13

X

Question 14

extrinsic pathway rapidly forms thrombin within…

Answer 14

15 sec

Question 15

(extrinsic/intrinsic) pathway starts first

Answer 15

extrinsic

Question 16

—— acts as the enzyme converting TF to its tenase

Answer 16

VII

Question 17

acts as a bridge in reactions of secondary hemostasis

Answer 17

Ca

Question 18

because the extrinsic pathway’s tenase is rapidly inactivated by ————-, the intrinsic pathway is needed

Answer 18

tissue factor pathway inhibitor (TFPI)

Question 19

2 functions of tenase

Answer 19

• activate X
• activate IX

Question 20

2 ways intrinsic pathway can be activated

Answer 20

• tenase activates IX
• XI activated by thrombin, which will then activate IX

Question 21

in vitro, XIIa activates —–, but this does not seem to happen in the body

Answer 21

XI

Question 21

IXa acts as a ————- that utilizes ——– from plts to form a complex with ———-

Answer 21

serine protease
PF3
VIII

Question 22

Xa acts as a ———— which utilizes phospholipids to form a complex with ——, called the —————

Answer 22

serine protease
V
prothrombinase

Question 23

factor II

Answer 23

prothrombin

Question 24

activates prothrombin

Answer 24

prothrombinase

Question 25

thrombin acts as a --------------- to convert...

Answer 25

serine protease fibrinogen to fibrin

Question 26

-------- is activated by thrombin to crosslink "D" portions of fibrin

Answer 26

XIII

Question 27

stages of fibrin development

Answer 27

1. fibrinogen—D-E-D molecules with A & B peptides attached to E 2. fibrin monomer—thrombin cleaves off A and B 3. fibrin polymer—D-E-D molecules spontaneously attach 4. stabilized fibrin polymer—XIIIa crosslinks D portions

Question 28

activated factors must stay ----------- so as not to cause clotting elsewhere how?

Answer 28

localized - vasoconstriction & vasodilation - fibrin seal, active factors contained in plug - inhibitory proteins bind activated factors - liver clearance of factors complexed with inhibitors

Question 29

examples of positive feedback in coagulation

Answer 29

- thrombin promotes release of plt factor Va - thrombin activates V and VIII - Xa activates VII and VIII

Question 30

examples of negative feedback in coagulation

Answer 30

- thrombin inactivates Va and VIIIa at higher conc - Xa inactivates VII - fibrin formation limits available thrombin - FDPs inhibit fibrin formation

Question 31

functions of thrombin

Answer 31

- irreversible plt aggregation - fibrinogen → fibrin - activates V, VIII, XI, XIII - downregulation of coagulation when bound to thrombomodulin + protein C

Question 32

coagulation inhibitors

Answer 32

- antithrombin III - heparin cofactor II - protein C - protein S - tissue factor pathway inhibitor (TFPI) - thrombomodulin

Question 33

in vivo inhibition of thrombin and Xa

Answer 33

antithrombin III

Question 34

directly inhibits thrombin

Answer 34

heparin cofactor II

Question 35

inhibits Va and VIIIa

Answer 35

protein C

Question 36

cofactor to protein C

Answer 36

protein S

Question 37

vitamin K dependent anticoags

Answer 37

protein C + protein S

Question 38

protein ---- is synth in the liver protein ---- is synth by VECs

Answer 38

C S

Question 39

inhibits VIIa-TF complex and Va

Answer 39

TFPI

Question 40

TFPI synth

Answer 40

VECs

Question 41

binds thrombin giving it anticoagulant activity (activates protein C)

Answer 41

thrombomodulin

Question 42

thrombomodulin location

Answer 42

VEC surface

Question 43

adsorb onto clot when fibrin is formed

Answer 43

plasminogen plasminogen activators

Question 44

acts on fibrin to allow gradual dissolution

Answer 44

plasmin

Question 45

gradual, progressive process leading to reestablishment of blood flow

Answer 45

fibrinolysis + tissue repair

Question 46

FDPs

Answer 46

fibrin degradation products

Question 47

produced by fibrinolysis

Answer 47

FDPs

Question 48

FDP fate

Answer 48

cleared by the liver

Question 49

function of plasminogen

Answer 49

converted to plasmin for fibrinolysis

Question 50

activators of fibrinolysis in tissues & blood

Answer 50

**tissues** - t-PA - u-PA **blood** - plasminogen activators - XIIa - kallikrein

Question 51

t-PA u-PA

Answer 51

tissue/urokinase plasminogen activator

Question 52

released by VECs and action limited to site of fibrin clot

Answer 52

t-PA

Question 53

used in fibrinolysis & in vitro hemostasis

Answer 53

XII kallikrein

Question 54

exposed collagen with a negative charge provides a site for ------ attachment, which mediates endogenous activation of fibrinolysis

Answer 54

XII

Question 55

2 functions of HMWK

Answer 55

- prekallikrein → kallikrein - kallikrein activation of XII

Question 56

HMWK

Answer 56

high molecular weight kininogen

Question 57

other roles of XII, PK, and HMWK

Answer 57

kinin system complement system

Question 58

converts single chain u-PA to double chain u-PA, increasing efficiency of plasminogen activation

Answer 58

kallikrein

Question 59

it's hypothesized that protein C indirectly liberates...

Answer 59

t-PA from VECs, initiating fibrinolysis

Question 60

4 FDPs

Answer 60

X Y D E

Question 61

pathologic action of plasmin

Answer 61

degradation of fibrinogen, V and VIII

Question 62

nonspecific test for FDPs

Answer 62

immunoassay

Question 63

fragment X

Answer 63

D-E-D without small peptides from carboxyl end of alpha chains fibrinogen degradation

Question 64

fragment Y

Answer 64

D-E

Question 65

specific FDP indicating degradation of fibrin indicates...

Answer 65

D-dimer pathologic clotting occurred

Question 66

FDP detected on automated analyzer

Answer 66

D-dimer

Question 67

inhibitors of fibrinolysis

Answer 67

- plasminogen activator inhibitors (PAI-1/2) - 𝛼2 antiplasmin - 𝛼2 macroglobulin - thrombin activated fibrinolysis inhibitor (TAFI)

Question 68

inhibit t-PA and u-PA

Answer 68

PAI-1/2

Question 69

inhibits free plasmin, not bound to fibrin

Answer 69

𝛼2 antiplasmin

Question 70

2nd line plasmin inhibitor (backup)

Answer 70

𝛼2 macroglobulin

Question 71

removes binding site of plasminogen from fibrin activated by thrombin

Answer 71

TAFI

Question 72

PTT: -------- pathway PT: --------- pathway

Answer 72

intrinsic extrinsic

Question 73

lab tests are not physiological in that excess ------------ are added in both PT and PTT (not a limiting factor)

Answer 73

phospholipid

Question 74

only PT is abnormal

Answer 74

problem with extrinsic system

Question 75

only PTT is abnormal

Answer 75

problem with intrinsic system

Question 76

PT and PTT are both abnormal

Answer 76

problem with common pathway OR multiple factor problems (liver disease, DIC)