Heparin Anticoagulants I Flashcards
Where is heparin found?
Naturally occurring anticoagulant found in the granules of mast cells along with histamine and serotonin.
Is heparin acidic or basic?
Acidic
What is the structure of heparin like?
Heparin is a strongly acidic (highly ionized) mucopolysaccharide composed of repeating units of sulfated glucuronic acid and sulfated glucosamine.
It has both high and low MW components.
What is the weight of 1 unit of heparin?
12 µg
What are the effects 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)
- Causes a release of tissue factor pathway inhibitor (TFPI)
How is heparin administered?
IV and subcutaneous
What is used for monitoring of heparin?
The anticoagulant effect is carefully monitored using the APTT method to determine the dose.
What is the therapeutic goal for heparin?
The therapeutic range is achieved when the APTT falls between 2.0-2.5 times the patients baseline.
What is the onset of action of heparin like?
It is rapid.
MOA of heparin
Heparin binds to AT III and induces a conformational change in AT III resulting in 1000x greater binding affinity to clotting factor proteases.
What are the pharmokinetics of heparin?
It is dose dependent. Increased doses will increase it’s half life.
What is the main co-factor for heparin that allows it to enact its function?
Antithrombin III
What are some of the other cofactors of heparin besides AT III?
Heparin Cofactor II
TFPI
Platelet Factor 4 (heparin neutralizing protein)
What are the main SE of heparin?
Hemorrhage
Heparin induced thrombocytopenia
Osteoporotic manifestation with spontaneous fracture
Alopecia
What is heparin induced thrombocytopenia?
HIT causes the generation of antiheparin platelet factor 4 antibodies. These antibodies activate platelets and endothelial cells.
What are the 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 is the use of protamine sulfate?
Protamine is a powerful heparin antagonist. It has a low molecular weight and is a highly basic protein that combines with strongly acidic heparin to form a stable salt with loss of anticoagulant activity.
How much protamine is needed to neutralize one unit of heparin?
10 µg
What may be some effects of IV administration of protamine?
Fall in blood pressure
Bradycardia
A patient was initially administered with 25,000 units of heparin for a surgical procedure. Forty minutes after the surgical procedure, he was administered with an additional 10,000 units of heparin. The surgical procedure was completed in 100 minutes and the patient was found to have 8700 units of heparin in his circulation. How much protamine is needed to neutralize this circulating heparin? A. 87 mg B. 807 mg C. 870 mg D. 8700 mg E. 0.87 mg
A. 87 mg
What are LMW heparins?
Prepared by fractionation or depolymerization of native heparin so only the lowest weight polypeptides remain
What is the difference in bioavailability of LMW heparin and normal heparin?
Low molecular weight heparins are bioavailable at 100% whereas heparin has a limited bioavailability (~30%)
What are the other advantages of LMW heparin?
Longer duration of action
Less bleeding
Lesser thrombocytopenia
What are some clinical uses of LMW heparin?
- Prophylaxis of DVT
- Treatment of DVT
- Management of acute coronary syndromes
- Other uses such as anticoagulation for surgical and interventional cardiovascular procedures
What is antithrombin concentrate used for?
This concentrate is used to treat patients with acquired or congenital antithrombin-deficiency. AT is also useful in sepsis and disseminated intravascular coagulation.
What is the use of hirudin?
Currently r-hirudin is used in the anticoagulant management of heparin induced thrombocytopenic patients.
What is the use of argotroban?
Argatroban is a synthetic antithrombin agent which is currently used as an anticoagulant in patients who can not be treated with heparin, special usage in the management of heparin induced thrombocytopenia.
Unlike heparin and hirudin, antibodies to argotroban are NOT formed.
What is the use of bivalirudin?
This agent is a hybrid molecule between a component of hirudin and a tripeptide. This drug is approved for PTCA anticoagulation.
Heparin MOA
Complex with AT and inhibits factors Xa and IIa.
Heparin main use
Surgical Anticoagulation
Heparin SE
Bleeding, HIT, osteoporosis, alopecia
LMW Heparin MOA
Complex with AT and inhibits factors Xa and IIa
LMW Heparin Monitoring Assay
Monitored by anti- Xa
LMW Heparin SE
Bleeding
LMW Heparin main use
Prophylaxis and Treatment of DVT and ACS
LMW Administration
Subcutaneous
Fondaparinux MOA (pentasaccharide)
Complex with AT and inhibits factor Xa
Fondaparinux Administration
Subcutaneous
Fondaparinux main uses
Management of DVT
Fondaparinux SE
Bleeding
Argatroban MOA
Directly Inhibits IIa
Argatroban Administration
IV
Argatroban main uses
Anticoagulant management of HIT patients
Argatroban SE
Bleeding
Bivalirudin MOA
Directly Inhibits IIa
Bivalirudin Administration
IV
Bivalirudin main uses
Anticoagulant management of HIT patients
Bivalirudin SE
Bleeding
Hirudin MOA
Directly Inhibits IIa
Hirudin Administration
IV
Hirudin main uses
Anticoagulant management of HIT patients
Hirudin SE
Bleeding
Antithrombin Concentrate MOA
Directly Inhibits IIa
Antithrombin Concentrate Administration
IV
Antithrombin Concentrate main uses
DIC, sepsis, thrombophilia, hypercoagulable state
Antithrombin Concentrate SE
None
Protamine Sulfate MOA
Heparin antagonist
Protamine Sulfate Administration
IV
Protamine Sulfate main uses
Heparin reversal
Protamine Sulfate SE
Bradycardia, hypotension
