Heparin Anticoagulants I

Question 1

True or false: Heparin’s composition varies in molecular weight

Answer 1

TRUE (composed of high and low molecular weight components)

Question 2

What is the source of heparin?

Answer 2

tissues rich in mast cells (beef lung and porcine intestine)

Question 3

What is the amount of 1 unit of heparin?

Answer 3

12ug

Question 4

What is the mechanism of action for heparin?

Answer 4

inhibits action of activated Xa and IIa (thrombin)

Question 5

What factor is thrombin?

Answer 5

IIa

Question 6

What activity of platelets is specifically inhibited by heparin?

Answer 6

aggregation of platelets

Question 7

What does heparin bind to?

Answer 7

Antithrombin III (resulting in 1000x greater binding affinity to clotting factor proteases)

Question 8

Name 3 big actions of heparin

Answer 8

1) plasma clearing (turbid plasma cleared of chylomicrons by release of lipase)
2) neutralizes positive charge of vascular lining
3) release of tissue factor pathway inhibitor (TFPI)

Question 9

What does TFPI bind to an inhibit?

Answer 9

factor 7 complex (activates extrinsic systems)

Question 10

What are the 2 routes of heparin administration?

Answer 10

1) IV

2) sub-cutaneous

Question 11

How do you monitor the anticoag effect of heparin?

Answer 11

APTT (therapeutic range is when APTT is 2-2.5x baseline)

Question 12

What is the APTT?

Answer 12

activated partial thromboplastin time (measure of the efficacy of the intrinsic coag pathway)

Question 13

What does PT measure?

Answer 13

prothrombin time (measure of the extrinsic pathway)

Question 14

How is heparin metabolized?

Answer 14

via heparinases in the liver

about 20-25% is excreted in the urine too

Question 15

What is the half life of heparin?

Answer 15

1-3 hours

Question 16

What is the onset of action of heparin?

Answer 16

5-10 mins

Question 17

the pharmacokinetics of heparin is ______ dependent

Answer 17

dose (increase the dose, increase the half life)

Question 18

What is the MAIN heparin cofactor?

Answer 18

antithrombin (AT)

Question 19

What are the 4 endogenous modulators of heparin?

Answer 19

1) AT
2) heparin cofactor II
3) TFPI
4) platelet factor 4

Question 20

True or false: a patient with a deficiency in AT will not respond to heparin

Answer 20

true

Question 21

What are 2 dangerous side effects of heparin?

Answer 21

1) hemorrhagic complications

2) heparin induced thrombocytopenia (HIT)

Question 22

What is HIT?

Answer 22

develop antibodies that activate platelets and endothelial cells (patients develop a thrombosis leading to gangrene)

Question 23

HIT specifically develops antibodies to ______

Answer 23

platelet factor 4

Question 24

What are 2 side effects of heparin?

Answer 24

1) Osteoporotic (brittle bones)

2) alopecia

Question 25

What are some clinical uses of heparin?

Answer 25

1) surgical/prophylactic anticoag
2) unstable angina
3) adjunct therapy with thrombolytic drugs
4) thrombotic and ischemic stroke

Question 26

What is the MAIN heparin antagonist?

Answer 26

Protamine sulfate (can neutralize heparin)

Question 27

Is heparin acidic or basic?

Answer 27

acidic (protamine is basic)

Question 28

One unit of heparin is neutralized by ______ of protamine

Answer 28

10ug

Question 29

How are low MW heparins prepared?

Answer 29

fractionation/depolymerization of native heparin

Question 30

What is the advantage to low MW heparins

Answer 30

bioavailability (100% vs heparin’s mere 30%)

longer duration of action

Question 31

When are low MW heparins used?

Answer 31

1) prophylaxis and treatment of DVT
2) acute coronary syndromes
3) anticoag

Question 32

What are the low MW heparins?

Answer 32

1) Lovenox

2) Enoxaparin

Question 33

How do you treat patients with AT deficiency?

Answer 33

AT concentrate

Question 34

When else do you use AT concentrate

Answer 34

sepsis and DIC (disseminated intravascular coag)

Question 35

What is the important protein found in the saliva of a leech?

Answer 35

hirudin (keeps blood flowing - anticoag)

Question 36

What is the commercial prep of hirudin?

Answer 36

refludan (used to treat HIT)

Question 37

What is the anti-thrombin agent that is used when patients cannot be treated with heparin (like in HIT)

Answer 37

argatroban (don’t worry about antibody formation)

Question 38

What are the 3 drugs that are thrombin inhibitors?

Answer 38

1) hirudin
2) argatroban
3) bivalirudin

DO NOT REQUIRE A COFACTOR

Question 39

When do you use bivalirudin

Answer 39

PTCA anticoag