(THER) Heparin Anticoagulants I Flashcards
Heparin is a naturally anticoagulant found in…
The granules of mast cells
What is the structure of Heparin? How much of its weight is used for anticoagulation?
What is the purpose of its structure?
Heparin is a strongly acidic mucopolysaccharide. It has a pentasaccharide sequence, which is needed for it to bind to its cofactor antithrombin-III
Only about 1/3rd of the weight of heparin has anticoagulative effects.
Why must heparin be standardized before it is distributed?
It is usually extracted from porcine intestines and there are many different types of pigs. As a result there is a variability in its molecular composition. Standerdization determines its anti-Xa and anti-IIa potencies.
How many micrograms make up a unit of heparin?
12 micrograms
1 mg = 120 units
Plasma clearing effect
One of the actions of Heparin. Heparin releases lipase which acts as a detergent to break down chylomicrons in the blood
What effect does heparin have on the vascular lining?
It binds to the lining, neutralizing its positive charge, thereby decreasing platelet ability to aggregate and form a clot.
Heparin and tissue factor pathway inhibitor
Among other functions, Heparin can cause endothelial cell release of TFPI. This blocks extrinisic system activation of the coagulation cascade.
What is the goal APTT result which tells you that heparin is within therapeutic range?
2.0-2.5 times the baseline
How is heparin metabolized? What is the key enzyme involved?
Most of it is metabolized by heparinase in the liver.
What is the half-life of heparin and how is it effected by the dose? What is its rate of onset? (rapid or slow)
The half-life is 1-3 hours and the onset of action is 5-10 minutes (rapid onset). As the dose is increased, the half-life increases accordingly.
What endogenous modulator can serve to neutralize Heparin? What pathological condition can result from this?
Platelet factor 4
Heparin Induced Thrombocytopenia (HIT) can result due to generation of antiheparin platelet factor 4 antibodies. These antibodies activate platelets and endothelial cells, causing a localized aggregation, ischemia and systemic thrombocytopenia.
What is protamine and how does it function?
Protamine is a powerful heparin antagonist. It is a highly basic protein and it combines with the strongly acidic heparin to form a stable salt, thereby negating heparin’s anticoagulant activity.
What is the dosing of protamine in comparison to heparin?
it’s a 1 gram to 1 gram ratio. One unit of heparin is thereby neutralized by 10 micro grams of protamine.
How does the structure of the synthesized low molecular weight heparin differ from native heparin? How do they differ in bioavailability?
They only contain the anticoagulation component (unlike heparin which is only 1/3rd anticoagulant). As a result, they have a 100% bioavailability.
What is the clinical advantage of LMW Heparins? What is the risk of LMW and HIT?
- Better bioavailability
- Longer duration of action
- Less bleeding
- Lesser thrombocytopenia
You should still not give LMW to patients with a history of HIT due to potential cross-reactivity of antibodies
