Heparin Anticoagulants I Flashcards Preview

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Flashcards in Heparin Anticoagulants I Deck (45)
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where is heparin naturally found

in the granules of MAST cells (along with histamine and serotonin)


chemically what is heparin made up of

strongly acidic (highly ionized) mucopolysaccharide composed of repeating units of sulfated glucuronic acid and sulfated glucosamine.

is heterogenous - found in different weights


what part of heparin is required to bind its co-factor

penta-saccaride sequence


why is there variation in heparin

comes from swine and different species produce different potencies of heparin


what 2 methods are used to standarize heparin

anti-Xa and anti-IIa assays


how is heparin dosed

in units

1 unit equals 8-12mg depending on potency


Actions of Heparin

Inhibits the action of activated factor Xa and factor IIa (Thrombin).

Inhibits the action of several other serine protease enzymes (XIIa, XIa).

Inhibits the aggregation of platelets (at high concentration).

Plasma clearing effect

Binds to vascular lining and neutralizes the positive charge.

Causes a release of Tissue Factor Pathway Inhibitor (TFPI).


heparin mainly affects which pathway

intrinsic (contact activation) pathway


heparin's MOA

Heparin binds to AT III and induces a conformational change in AT III resulting in 1000x greater binding affinity to clotting factor proteases.


heparin requires what co-factor

antithrombin III


plasma clearing affect of heparin

Turbid plasma is rapidly cleared of fat chylomicrons by a release of lipase from the blood vessels.


heparin's route of administration

IV and subcutaneous (mostly used inpatient)

not absorbed orally or rectally


APTT therapeudic range for heparin

2- 2.5 times baseline


how do you monitor heparin

APTT (effects are not well correlated with patient weight)


what enzyme metabolizes heparin

heparinase in the liver


how is heparin excreted

20-25% of heparin is excreted in urine


what happens to heparin that is not excreted

Some heparin is picked up by mast cells

Endothelium is able to bind heparin


what is the duration and onset of heparin

Biologic T 1/2 of intravenous heparin is 1-3 hours, depending on the dose. (dose dependent effect)

Onset of action is 5-10 minutes (as measured by APTT method).


Endogenous modulators of heparin action (what affects heparin's actions)

AT(main heparin co-factor) needed for heparin to have affects

Heparin cofactor II (second cofactor) can only inhibit thrombin when heparin binds

Tissue Factor Pathway Inhibitor (TFPI)
Platelet factor 4 (heparin neutralizing protein)


Side Effects of Heparin

Hemorrhagic complications
 (Adrenal, gut, etc.)
Heparin induced thrombocytopenia (HIT)


Heparin induced thrombocytopenia (HIT)

Generation of antiheparin platelet factor 4 antibodies. (Ab to the complex) These antibodies activate platelets and endothelial cells.

can lead to limb loss - monitor platelet counts for drops of around 50%


clinical uses of heparin

Therapeutic anticoagulation
Surgical anticoagulation
Prophylactic anticoagulation
Unstable angina and related coronary syndromes
Adjunct therapy with thrombolytic drugs
Thrombotic and ischemic stroke



is a powerful heparin antagonist. It has a low molecular weight and is a highly basic protein found in the sperm of certain fish.

It combines with strongly acidic heparin to form a stable salt with loss of anticoagulant activity. (an advantage to using heparin is that an antagonist is available)


how much protamine is needed to neutralized 1 unit of heparin?

about 10 ug

2500 units is neutralized by 25 mg


Low Molecular Weight Heparins & Synthetic Heparin Pentasaccharide are made by

Prepared by fractionation or depolymerization of native heparin.


bioavailability of LMW heparin vs heparin

LMW heparin 100% (advantage it can be given orally)



Clinical Advantages of LMW Heparins

* Better bioavailability
* Longer duration of action
Less bleeding
Lesser thrombocytopenia


do LMW heparins require a co-factor

yes! they still require AT III


clinical uses of LMW heparin

Prophylaxis of DVT (once a day dosing advantage over heparin)
Treatment of DVT (can be sent home on it)
Management of acute coronary syndromes
Other uses such as anticoagulation for surgical and interventional cardiovascular procedures


Antithrombin- Concentrates (AT) uses

Antithrombin-concentrate is used to treat patients with acquired or congenital antithrombin-deficiency AT is also useful in *sepsis and *disseminated intravascular coagulation

pts with AT III deficiencies are more prone to DIC and sepsis