coagulation

Question 1

coagulation cascade is a successive series of?

Answer 1

amplifying enzymatic reactions

Question 2

at each step in the coagulation cascade a proenzyme is?

Answer 2

proteolyzed to become an active enzyme, which in turn proteolyzes the next proenzyme

Question 3

the end goal of the coagulation cascade leads to the activation of?

Answer 3

thrombin and the formation of fibrin

Question 4

each reaction of the coagulation cascade depends on the assembly of what 3 complex components?

Answer 4

• enzyme = activation coagulation factor
• substrate= a proenzyme form of the next coagulation factor in the series
• co-factor = a reaction accelerator

Question 5

components of the coagulation cascade are assembled where? held together how?

Answer 5

on phospholipid surface and held together by calcium-dependent interactions

Question 6

the ability of factors 2, 7, 9 and 10 to bind to calcium requires what vitamin?

Answer 6

vitamin K

Question 7

coumadin and warfarin are?

Answer 7

anticoagulants

Question 8

Major Cascade Event

Answer 8

1) activation of factor X to Xa
2) factor Xa catalyzes the conversion of prothrombin to thrombin
3) thrombin converts soluble fibrinogen to insoluble fibrin, which is stabolized by factor 13
4) stailized fibrin ‘glues’ platelet plug for greater endurance

Question 9

describe tissue factor (extrinsic) pathway

Answer 9

• occurs after vascular damage
• activated by factor 3 (tissue factor) which is exposed at sites of injury
• TF complexes with Factor 7a (extrinsic factor Xase), converging with the intrinsic pathway, leading to the activation of factor X to Xa

Question 10

describe contact activation (intrinsic) pathway

Answer 10

• TF- factor 7a complex activates factor 9 and 9a
• factor 9a complexes with 8a (“intrinsic factor Xase”)
• also activated by factor 12 (Hageman factor)
• may be activated in the absence of tissue injury
• important in the pathogenesis of thrombosis

Question 11

both intrinsic and extrinsic pathways converge to activate?

Answer 11

factor 10

Question 12

describe common pathway

Answer 12

1) factor 10 is activated by factor 9a-8a complex (intrinsic factor Xase) and TF-factor 7a (extrinic factor Xase)
2) factor 10a-5a complex activate factor 2 (prothrombin) to 2a (thrombin)
3) thrombin converts fibrinogen (factor 1) to fibrin (1a)
4) fibrin clot stabilized by factor 13a

Question 13

what is INR?

Answer 13

international normalized ratio = standardized measurement and expression of the prothrombin time

• patient PT/ mean normal PT)^ISI
• normal is 0.9-1.2
• adequate anti-coagulation generally 2.0-3.0, as high as 3.5 for high-risk conditions

Question 14

INR is used to monitor for?

Answer 14

coumadin (warfarin) anticoagulation and screening for coagulopathies

Question 15

INR reflects the activites of what factors?

Answer 15

2, 5, 7, and 10

Question 16

Dental Procedures and Warfarin

Answer 16

use them! more so for outpatient dental surgery procedures like extraction or root canals
*both ACCP and BCSH agree

Question 17

counter clotting mechanisms are set in motion simultaneously with?

Answer 17

clot formation to limit clotting to the site of injury

Question 18

name 3 natural anticoagulants

Answer 18

1) antithrombins aka antithrimbin 3
2) Protein C and S
3) tissue factor pathway inhibitor (TFPI)

Question 19

antithrombins aka antithrimbin 3 inhibit ____ and what factors?

Answer 19

inhibit thrombin and factors 9a, 10a, 11a, and 12a

Question 20

antithrombins are activated by?

Answer 20

binding to heparin-like molecules on endothelial cells

Question 21

ATT3 inhibits what?

Answer 21

inhibits thrombin and factors 9a and 10a

Question 22

exogenous heparin binds to ____ resulting in its activation

Answer 22

ATT3

Question 23

Protein C and S are vitamin ____ dependent and INactivates what factor?

Answer 23

vitamin K

*inactivates thrombin and factors 9a and 10a

Question 24

1) fibrinolytic cascade limits size of?
2) fibrinolytic cascade mediated by?
3) fibrin split prodcuts (FSPs) act as ?
4) elevated FDPs are useful for?

Answer 24

1) the final clot
2) mediated by plasmin
3) fibrin split products (FSPs) can act as weak anticoagulants
4) elevated FSPs areful in diagnosing abnormal thrombotic states

Question 25

plasmin is formed by?

Answer 25

cleaving plasminogen to plasmin by plasminogen activators

Question 26

tissue plasminogen activator (tPA) is made by? most active when?

Answer 26

endothelial cells | *most active when attached to fibrin

Question 27

uPA stands for?

Answer 27

urokinase-like plasminogen activator; another activator of plasminogen

Question 28

uPA and tPA are inactivated by?

Answer 28

alpha2- antiplasmin

Question 29

plasminogen activator inhibitors do what?

Answer 29

block fibrinolysis * increased production by inflammatory cytokines (IF-y) * modulates coagulation-anticoagulation balance

Question 30

define thrombosis

Answer 30

formation of blood clot in injured vessels | *pathologic converse to hemostasis

Question 31

virchow's triad of pathogenesis of thrombosis

Answer 31

1) endothelial injury 2) stasis or turbulent blood flow 3) hypercoagulability

Question 32

endothelial injury is an important cause of?

Answer 32

thrombosis

Question 33

loss of endothelium > exposure of subendothelial ECM > ____ > _____ > reduced production of ____ and ____

Answer 33

``` loss of endothelium > exposure of subendothelial ECM > plateletadhesion > release ofTF > reduced production of prostacyclin (PGI2) and plasminogen activators ```

Question 34

T or F... Endothelium does not need to be denuded or physically disrupted to contribute to development of a thrombus

Answer 34

TRUE

Question 35

dysfunction endothelium elaborates greater or decreased amounts of procoagulant factors or anticoagulant molecules

Answer 35

* greater procoagulant factors | * decreased anticoagulant molecules

Question 36

endothelial dysfunction can be mediated by?

Answer 36

hypertension (high BP), turbulent blood flow, bacterial products (endotoxin), radiation, hypercholesterolemia, cigarette smoking

Question 37

two major categories of abnormal blood flow we discussed

Answer 37

1) turbulence | 2) stasis and turbulence

Question 38

describe turbulence? major factor in?

Answer 38

* causes endothelial injury or dysfunction * formation of countercurrents and local pockets of stasis, major factor in the formation of DVTs (deep vein thrombosis, often in legs)

Question 39

describe stasis AND turbulence?

Answer 39

* promote endothelial activation * platelets and WBCs in contact with endothelium * slows dilation of activated clotting factors * impedes inflow of clotting factor inhibitors * BF slows down

Question 40

two types of hypercoagulability

Answer 40

1) primary (genetic) | 2) secondary (acquired)

Question 41

define hypercoagulability

Answer 41

infrequent contributor to arterial or intracardiac thrombosis **important risk factor for venous thrombosis

Question 42

primary (genetic) hypercoagulability is most often caused by?

Answer 42

mutations in factor 5 and prothrombin genes

Question 43

Leiden mutation= factor ____ mutation

Answer 43

5

Question 44

factor 5 becomes resistant to what in a Leiden mutation?

Answer 44

protein C

Question 45

``` ____% of Caucasians carry a specific factor V mutation (Leiden mutation). ```

Answer 45

2-15%

Question 46

G to A single-nucelotide substitution of the | prothrombin gene increases?

Answer 46

prothrombin transcription

Question 47

G to A single-nucelotide substitution of the | prothrombin gene is in ____% of population

Answer 47

1-2%

Question 48

People are more at risk for a G to A single-nucelotide substitution of the prothrombin gene mutation when?

Answer 48

pregnant, prolonged bedrest, long plane rides

Question 49

primary (genetic) hypercoagulability has less common inherited deficiencies concerning?

Answer 49

anticoagulents - antithrombin 3 - protein C - protein S

Question 50

Congenitally elevated levels of homocysteine > ____ and ____ thromboses

Answer 50

arterial and venous thromboses

Question 51

primary (genetic) hypercoagulability are present with ____ thromboses and?

Answer 51

Present with venous thrombosis and recurrent thromboembolism

Question 52

secondary (acquired) hypercoagulability is associated with other disease states such as:

Answer 52

■ Cardiac failure or prolonged bed rest (stasis) ■ Surgery or trauma (vascular injury) ■ Estrogen (increase hepatic production of coagulation factors and decrease production of antithrombin III) ■ Cancer (procoagulant tumor products) ■ Advanced age (increase platelet aggregation and decrease release of prostacyclin (PGI2) ■ Smoking ■ Obesity

Question 53

Heparin-induced thrombocytopenia (HIT) | syndrome and Anti-phospholipid antibody syndrome are primary or secondary hypercoagulability?

Answer 53

secondary (acquired) hypercoagulability

Question 54

Heparin-induced thrombocytopenia (HIT) | syndrome:

Answer 54

■ 5% of patients treated with unfractionated heparin. ■ Autoantibodies bind complexes of heparin and platelet membrane protein. ■ Cross-react with similar complexes on platelets and endothelial cells → platelet aggregation, activation, consumption and endothelial cell injury.

Question 55

Anti-phospholipid antibody syndrome

Answer 55

``` ■ Thromboses, miscarriages, cardiac valve vegetations and thrombocytopenia. ■ PE, pulmonary HTN, stroke, bowel infarction or renovascular HTN. ■ Renal microangiopathy → renal failure. ```

Question 56

Anti-Phospholipid Antibodies bind to what to create a hypercoagulable state

Answer 56

Bind to beta-2 glycoprotein I and prothrombin → hypercoagulable state

Question 57

In vitro Anti-Phospholipid Antibodies interfere with phospholipids causes an inhibition of?

Answer 57

inhibit coagulation

Question 58

what creates False-positive serologic test for syphilis?

Answer 58

Anti-Phospholipid Antibodies

Question 59

In vivo Anti-Phospholipid Antibodies interfere with phospholipids promotes?

Answer 59

promotes coagulation

Question 60

T or F... Anti-Phospholipid Antibody Syndrome has primary and secondary forms.

Answer 60

true

Question 61

secondary form of Anti-Phospholipid Antibody Syndrome is associated with?

Answer 61

associated with an autoimmune | disease (SLE)

Question 62

primary form of Anti-Phospholipid Antibody Syndrome is associated with?

Answer 62

only exhibit manifestations of | hypercoagulable state.

Question 63

Anti-Phospholipid Antibody Syndrome may appear following exposure to?

Answer 63

drugs or infections

Question 64

Anti-Phospholipid Antibody Syndrome may be noted in ____% of apparently normal individuals

Answer 64

5-15%

Question 65

treatment of Anti-Phospholipid Antibody Syndrome is?

Answer 65

Anticoagulation and immunosuppression