Anticoagulants: coag cascade and heparins

Question 1

What are coagulation factors?

Answer 1

Enzymes

Question 2

What happens as the steps of coagulation go on?

Answer 2

The initial signal is amplified

Question 3

Where is the coagulation cascade made?

Answer 3

In the liver

Question 4

What does the final pathway of the coagulation cascade result in?

Answer 4

Conversion of prothrombin (II) to thrombin

Question 5

What does the conversion of prothrombin to thrombin catalyze

Answer 5

Conversion of fibrinogen to fibrin

Question 6

What does fibrin activate?

Answer 6

Plasmin and tissue plasminogen activator (t-PA)

Question 7

What balance maintains homeostasis

Answer 7

The balance of procoagulants (coag factors) and endogenous anticoagulants

Question 8

Give some examples of endogenous anticoagulants

Answer 8

Proteins C and S

Antithrombin III

Question 9

What are proteins C and S important for

Answer 9

Warfarin dosing

Question 10

What is antithrombin III important for?

Answer 10

Heparin dosing

Question 11

What does the fibrinolytic system do?

Answer 11

Degrades fibrin

Question 12

What does the degradation of fibrin result in?

Answer 12

Fibrin split products (FSP)
Fibrin Dimers (d-dimer)

Question 13

What are fibrin split products also known as

Answer 13

Fibrin degradation products (FDPs)

Question 14

What do increased levels of FSP, FDPs, and d-dimers suggest?

Answer 14

Presence of thrombi

think DVT

Question 15

What are some examples of venous thrombi?

Answer 15

DVT
“Red thrombus”
Venous stasis thrombi

Question 16

What is a complication of venous thrombi?

Answer 16

Pulmonary embolus

Question 17

What are some examples of arterial thrombi?

Answer 17

Platelet driven

“White thrombus”

Question 18

What are some complications of arterial thrombi?

Answer 18

Stroke

MI

Question 19

Recall virchow’s triad

Answer 19

Hypercoaguable state
Endothelial injury
Circulatory stasis

Question 20

List some risks for thrombosis

Answer 20

Surgery
Cancer
Immobility
Varicose veins
Pregnancy

Question 21

What is a potential complication of anticoagulation agents?

Answer 21

Bleeding

Question 22

Is bleeding from an anticoagulant an allergy?

Answer 22

No!

Just an extension of their MOA

Question 23

What is the MOA of heparin

Answer 23

It binds to antithrombin III

AT III

Question 24

What is required for heparin binding

Answer 24

A specific pentasaccharide sequence

Question 25

Heparin limitations

Answer 25

look at slides 20 and 21

Question 26

What is unfractionated heparin (UFH)

Answer 26

A heterogeneous mix of sulfated glycosaminoglycans

Question 27

What portion of UFH have the pentasaccharide?

Answer 27

1/3

Question 28

How much more anticoagulant does UFH antithrombin complexes have than just antithrombin alone?

Answer 28

100-1000x more

Question 29

What is UFH effective on?

Answer 29

Soluble fibrin -> not clot bound

Question 30

What does UFH do to the thrombus?

Answer 30

Prevents growth/propagation

Question 31

What does UFH allow the pt's system to do?

Answer 31

Allows pt's fibrinolytic system to degrade the clot

Question 32

How do we measure UFH

Answer 32

By the activated Partial Thromboplastin Time (aPTT)

Question 33

What kind of heparin is used as DVT prophylaxis

Answer 33

subq UFH

Question 34

How much subq UFH is used as DVT prophylaxis

Answer 34

5000 units q12 or q8

Question 35

What is the risk of heparin induced thrombocytopenia (HIT) with SubQ UFH for DVT prophylaxis?

Answer 35

It is that of IV UFH | *increased risk

Question 36

List some advantages of UFH

Answer 36

Immediate anticoagulants Measured by aPTT Has a reversing agent (Protamine)

Question 37

List some disadvantages of UFH

Answer 37

Non-linear kinetics Frequent lab testing needed Increased risk of bleeding

Question 38

What is Protamine sulfate used for

Answer 38

Reverse UFH

Question 39

What is the MOA of Protamine

Answer 39

combines w/ strongly acidic heparin

Question 40

Is HIT I immune or non-immune

Answer 40

Non-immune

Question 41

HIT I prevalence

Answer 41

10% of pts

Question 42

HIT I description

Answer 42

Ok -> not very concerning | Transient due to clumping of platelets -> usually an artifact

Question 43

How quickly does HIT I happen?

Answer 43

Immediately

Question 44

Is HIT II immune or non-immune

Answer 44

Immune | Mediated by anti-platelet factor 4

Question 45

Prevalence of HIT II

Answer 45

<3%

Question 46

HIT II description

Answer 46

Happens 5-10 days after heparin | Platelet count falls by >50% from baseline

Question 47

If pt has HIT II what do you test for?

Answer 47

PF4

Question 48

How do you reduce the risk of HIT w/ a pt with low molecular weight heparin?

Answer 48

When this is the first heparin started in the pt

Question 49

How is low molecular weight heparin (LMWH) dosed?

Answer 49

Weight based linear dosing

Question 50

How do you administer LMWH?

Answer 50

SubQ

Question 51

What is an available LMWH agent?

Answer 51

Enoxaparin

Question 52

When are LMWH agents indicated?

Answer 52

ACS tx DVT PE VTE prophylaxis in high risk populations

Question 53

List some advantages of LMWH

Answer 53

More favorable benefit/risk ratio More predictable dose response ratio No IV access required No routine testing

Question 54

List some disadvantages of LMWH

Answer 54

SubQ administration causes pain Testing requires anti-Xa -> not readily available Possible upper weight max No protamine reversal

Question 55

Enoxaparin dosing for acute DVT w/ or w/o PE in an inpatient setting

Answer 55

1 mg/kg/dose (rounded) SubQ q12 hours | 1.5 mg/kg (rounded) SubQ once daily

Question 56

Enoxaparin dosing for acute DVT w/ or w/o PE in an outpatient setting

Answer 56

1 mg/kg/dose (rounded) SubQ q12

Question 57

Is LMWH more or less costly than UFH?

Answer 57

Less

Question 58

Is the risk of HIT higher or lower with LMWH than UFH?

Answer 58

Lower risk of HIT