Heparin Anticoagulants I Flashcards
True or false: Heparin’s composition varies in molecular weight
TRUE (composed of high and low molecular weight components)
What is the source of heparin?
tissues rich in mast cells (beef lung and porcine intestine)
What is the amount of 1 unit of heparin?
12ug
What is the mechanism of action for heparin?
inhibits action of activated Xa and IIa (thrombin)
What factor is thrombin?
IIa
What activity of platelets is specifically inhibited by heparin?
aggregation of platelets
What does heparin bind to?
Antithrombin III (resulting in 1000x greater binding affinity to clotting factor proteases)
Name 3 big actions of heparin
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)
What does TFPI bind to an inhibit?
factor 7 complex (activates extrinsic systems)
What are the 2 routes of heparin administration?
1) IV
2) sub-cutaneous
How do you monitor the anticoag effect of heparin?
APTT (therapeutic range is when APTT is 2-2.5x baseline)
What is the APTT?
activated partial thromboplastin time (measure of the efficacy of the intrinsic coag pathway)
What does PT measure?
prothrombin time (measure of the extrinsic pathway)
How is heparin metabolized?
via heparinases in the liver
about 20-25% is excreted in the urine too
What is the half life of heparin?
1-3 hours
What is the onset of action of heparin?
5-10 mins
the pharmacokinetics of heparin is ______ dependent
dose (increase the dose, increase the half life)
What is the MAIN heparin cofactor?
antithrombin (AT)
What are the 4 endogenous modulators of heparin?
1) AT
2) heparin cofactor II
3) TFPI
4) platelet factor 4
True or false: a patient with a deficiency in AT will not respond to heparin
true
What are 2 dangerous side effects of heparin?
1) hemorrhagic complications
2) heparin induced thrombocytopenia (HIT)
What is HIT?
develop antibodies that activate platelets and endothelial cells (patients develop a thrombosis leading to gangrene)
HIT specifically develops antibodies to ______
platelet factor 4
What are 2 side effects of heparin?
1) Osteoporotic (brittle bones)
2) alopecia
What are some clinical uses of heparin?
1) surgical/prophylactic anticoag
2) unstable angina
3) adjunct therapy with thrombolytic drugs
4) thrombotic and ischemic stroke
What is the MAIN heparin antagonist?
Protamine sulfate (can neutralize heparin)
Is heparin acidic or basic?
acidic (protamine is basic)
One unit of heparin is neutralized by ______ of protamine
10ug
How are low MW heparins prepared?
fractionation/depolymerization of native heparin
What is the advantage to low MW heparins
bioavailability (100% vs heparin’s mere 30%)
longer duration of action
When are low MW heparins used?
1) prophylaxis and treatment of DVT
2) acute coronary syndromes
3) anticoag
What are the low MW heparins?
1) Lovenox
2) Enoxaparin
How do you treat patients with AT deficiency?
AT concentrate
When else do you use AT concentrate
sepsis and DIC (disseminated intravascular coag)
What is the important protein found in the saliva of a leech?
hirudin (keeps blood flowing - anticoag)
What is the commercial prep of hirudin?
refludan (used to treat HIT)
What is the anti-thrombin agent that is used when patients cannot be treated with heparin (like in HIT)
argatroban (don’t worry about antibody formation)
What are the 3 drugs that are thrombin inhibitors?
1) hirudin
2) argatroban
3) bivalirudin
DO NOT REQUIRE A COFACTOR
When do you use bivalirudin
PTCA anticoag
