Heparin Anticoagulants Flashcards
What kinds of cell is heparin found in?
Mast cells (along with histamine and serotonin)
Heparin
Acidic or Basic? Is it a protein, lipid, sugar?
Strongly acidic
Mucopolysaccharide with repeating units of glucoronic acid and sulfated glucosamine
What is the average size of heparin?
12 kDa, but can range from 2-40 kDa
What animal do we mainly get our heparin from?
Pigs!
Different species produce slightly different heparin.
How do we standardize heparin acquired from different pigs?
Anti-Xa and Anti-IIa methods
Heparin is dosed in units, not grams. I mg of heparin is about equal to…
120 USP units
Heparin
Mechanism of Action
Inhibits action of activated Factor Xa and Factor IIa
Also interacts with XIIa and XIa
Inhibits aggregation of platelets (at high concs)
What does heparin bind in its normal MOA and how does that bring about anti coagulability?
Binds antithrombin III (ATIII)
Causes a conformation change in ATIII, making it more likely to block thrombin and other coag factors
What is the plasma clearing effect of heparin?
Releases lipoprotein lipase from blood vessels to break down fat chylomicrons
Heparin causes release of TFPI. What does this accomplish?
Inhibits tissue factor/VIIa complex, which would normally activate the extrinsic system
Heparin Administration
Only IV and Subcutaneous
Therapeutic Monitoring of Heparin
What test do you use? What is the therapeutic range?
Use the APTT (activated partial thromboplastin time) for monitoring
Therapeutic range is 2-2.5x baseline APTT
Heparin Elimination
Renal or metabolic (through liver heparinase enzymes)
Heparin
Duration of Action
Rapid onset (5-10 min) 1-3 hour half life
Higher dose –> longer half life
What are some endogenous modulators of heparin?
Antithrombin III (ATIII)
Heparin cofactor II
TFPI
Platelet Factor 4
Side Effects of Heparin
Hemorrhage (adrenals, gut)
Heparin induced thrombocytopenia (HIT), leading to thrombosis of superficial veins and gangrene
Osteoporosis
Alopecia (long term)
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
What drug is used as a heparin antagonist?
Protamine sulfate
Protamine Sulfate
Mechanism of Action
Protamine Sulfate is strongly basic. Combines with the acidic heparin and causes loss of anticoagulant activity
Protamine Sulfate
Dosage – how much Protamine sulfate is required to neutralize one USP unit heparin?
One USP unit heparin neutralized by 10 ug protamine sulfate
Protamine Sulfate is given IV. What can this cause?
Hypotension
Bradycardia
Give Protamine sulfate by slow infusion to prevent these
Low MW Heparins
How are they prepared?
Chemical and enzymatic degradation of heparin to make it more homogenous.
What does synthetic heparin pentasaccharide mimic?
The sequence of heparin that binds ATIII
Where are low MW heparins and synthetic heparin pentasaccharides commonly used?
Outpatient settings
Prophylaxis for certain surgeries (like knee or hip)
Prophylaxis and treatment of DVT
Low MW Heparin
Advantages over heparin
Better bioavailability (100%)
Longer duration of action
Less bleeding
Less thrombocytopenia
Antithrombin Concentrates
Clinical Uses
Patients with acquired or congenital antithrombin deficiency
Sepsis
DIC
Hirudin
Mechanism of Action
Clinical Uses
Thrombin inhibitor found in leech saliva.
Refludan is used clinically.
Used in management of HIT.
Argatroban
Mechanism of Action
Clinical Uses
Synthetic anti-thrombin agent used for HIT
Bivalirudin
Mechanism of Action
Synthetic anti-thrombin agent used for PTCA anticoagulation.
Also has anti-platelet effects.
