Anticoagulants Flashcards
What is the difference between an anticoagulant and
an antithrombotic?
Anticoagulants such as heparin and enoxaparin delay or
prevent the clotting of blood by interfering with the coagulant
system. Antithrombotic agents such as aspirin typically interfere
with with thrombus formation by interfering with the adherent or
aggregation properties of platelets.
Stoelting RK & Hillier SC. Pharmacology and Physiology in
Anesthetic Practice. 4th ed. Philadelphia, PA: Lippincott
Williams & Wilkins; 2006: 505.
What are the principal uses of heparin?
The treatment and prevention of deep vein thrombosis,
pulmonary embolus, mural thrombosis following myocardial
infarction, in the treatment of unstable angina and infarction,
and the prevention of thrombosis due to exposure of the blood
to extracorporeal circulation devices such as dialysis and
cardiopulmonary bypass.
Stoelting RK & Hillier SC. Pharmacology and Physiology in
Anesthetic Practice. 4th ed. Philadelphia, PA: Lippincott
Williams & Wilkins; 2006: 506.
How does heparin administration affect the
pharmacokinetics of diazepam and propranolol?
Heparin displaces alkaline drugs from their protein binding sites
and can increase the circulating concentrations and clinical
effects of these drugs.
Stoelting RK & Hillier SC. Pharmacology and Physiology in
Anesthetic Practice. 4th ed. Philadelphia, PA: Lippincott
Williams & Wilkins; 2006: 509.
Following the administration of heparin, a patient
develops fever, tachycardia, and urticaria. What do
you believe is occurring?
Because heparin is derived from animal sources, some patients
may be allergic to it. It should be used cautiously in patients
with known allergies to porcine or bovine derivatives.
Stoelting RK & Hillier SC. Pharmacology and Physiology in
Anesthetic Practice. 4th ed. Philadelphia, PA: Lippincott
Williams & Wilkins; 2006: 509.
What is HITT syndrome?
Heparin-induced thrombocytopenia and thrombosis syndrome,
which is a potentially life-threatening disorder that occurs in
about 5% of patients receiving heparin. The patient develops
severe thrombocytopenia, becomes resistant to the effects of
heparin, and may develop thombosis despite the low platelet
count. It usually develops after 6-10 days of heparin therapy. It
is due to the development of platelet-associated
immunoglobulin (IgG) antibodies.
Stoelting RK & Hillier SC. Pharmacology and Physiology in
Anesthetic Practice. 4th ed. Philadelphia, PA: Lippincott
Williams & Wilkins; 2006: 508.
What is the onset of action of IV heparin?
Subcutaneous?
The onset is immediate with intravenous heparin and 1-2 hours
when administered SQ.
Stoelting RK & Hillier SC. Pharmacology and Physiology in
Anesthetic Practice. 4th ed. Philadelphia, PA: Lippincott
Williams & Wilkins; 2006: 506.
What ACT value is considered indicative of adequate
heparinization for cardipulmonary bypass?
An ACT >300 seconds is considered adequate, 180-300
seconds is considered questionable, and less than 180 seconds
is considered inadequate.
Stoelting RK & Hillier SC. Pharmacology and Physiology in
Anesthetic Practice. 4th ed. Philadelphia, PA: Lippincott
Williams & Wilkins; 2006: 506.
What two laboratory values are used to measure the
efficacy of heparin therapy?
The activated plasma thromboplastin time (APTT) and the
activated coagulation time (ACT). The therapeutic range for the
APTT is considered to be 1.5-2.5 times the normal value of 30-
35 seconds. The ACT is used more commonly during surgical
procedures because of its ease of use.
Stoelting RK & Hillier SC. Pharmacology and Physiology in
Anesthetic Practice. 4th ed. Philadelphia, PA: Lippincott
Williams & Wilkins; 2006: 506.
What antihypertensive agent can increase the
required dose of heparin?
Nitroglycerin
Stoelting RK & Hillier SC. Pharmacology and Physiology in
Anesthetic Practice. 4th ed. Philadelphia, PA: Lippincott
Williams & Wilkins; 2006: 506.
What factors can prolong the half-life of heparin?
Hepatic dysfunction, renal dysfunction, and decreases in body
temeprature below 37 degrees Celsius
Stoelting RK & Hillier SC. Pharmacology and Physiology in
Anesthetic Practice. 4th ed. Philadelphia, PA: Lippincott
Williams & Wilkins; 2006: 505.
What is the elimination half-time of 100 U/kg of
intravenous heparin?
About 56 minutes
Stoelting RK & Hillier SC. Pharmacology and Physiology in
Anesthetic Practice. 4th ed. Philadelphia, PA: Lippincott
Williams & Wilkins; 2006: 505.
Why must heparin be administered by injection?
Heparin has a high molecular weight (ranging between 3,000
and 30,000 daltons) and is poorly lipid soluble. Because of this,
it is poorly absorbed from the gastrointestinal tract.
Stoelting RK & Hillier SC. Pharmacology and Physiology in
Anesthetic Practice. 4th ed. Philadelphia, PA: Lippincott
Williams & Wilkins; 2006: 505.
Where is heparin located naturally within the body?
It is located in basophils, mast cells, and the liver (from which it
derives its name).
Stoelting RK & Hillier SC. Pharmacology and Physiology in
Anesthetic Practice. 4th ed. Philadelphia, PA: Lippincott
Williams & Wilkins; 2006: 505.
How does heparin produce its anticoagulant effect?
It binds to antithrombin, a natural anticoagulant, and enhances
the ability of antithrombin to inactivate thrombin and activated
factors X, XII, IX, and XI by over 1000 times. Heparin also
inhibits platelet function.
Stoelting RK & Hillier SC. Pharmacology and Physiology in
Anesthetic Practice. 4th ed. Philadelphia, PA: Lippincott
Williams & Wilkins; 2006: 505.
What patients would have a higher risk for having an
allergic reaction to protamine?
Patients with a history of exposure to protamine zinc insulin and
men who have undergone vasectomies have an increased risk
for allergic reaction to protamine, especially if they have a
history of allergic reaction to the insulin. Also, because
protamine is derived from salmon milt, patients with a history of
allergy to fish products have an increased risk for allergic
reaction to protamine.
Longnecker DE, Newman MF, Brown DL, Zapol WM.
Anesthesiology. 2nd ed. New York: McGraw-Hill; 2012: 1489.
What are the contraindications to heparin
administration?
Heparin should not be administered to patients with a known
bleeding diathesis or those presenting for intraocular or
intracranial surgery.
Stoelting RK & Hillier SC. Pharmacology and Physiology in
Anesthetic Practice. 4th ed. Philadelphia, PA: Lippincott
Williams & Wilkins; 2006: 508.
How long after the administration of a low molecular
weight heparin should you wait prior to surgery?
Because they have a longer half-life than heparin and a risk of
bleeding that is nearly that of heparin, surgery should be
delayed until 12 hours after the last dose if at all possible.
Stoelting RK & Hillier SC. Pharmacology and Physiology in
Anesthetic Practice. 4th ed. Philadelphia, PA: Lippincott
Williams & Wilkins; 2006: 511.
How does protamine antagonize the effects of
heparin?
The positively charged and alkaline protamine binds with the
negatively-charged and acidic heparin molecule to form a highly
stable compound that has no anticoagulant properties.
Stoelting RK & Hillier SC. Pharmacology and Physiology in
Anesthetic Practice. 4th ed. Philadelphia, PA: Lippincott
Williams & Wilkins; 2006: 510.
What is the estimated dose of protamine required to
reverse the effects of heparin?
1 mg of protamine for every 100 units of heparin predicted to
still be circulating. (Remember that heparin has a half-life of
about an hour)
Stoelting RK & Hillier SC. Pharmacology and Physiology in
Anesthetic Practice. 4th ed. Philadelphia, PA: Lippincott
Williams & Wilkins; 2006: 510.
What are the potential side effects of rapid
administration of heparin?
Histamine release with associated hypotension, flushing,
tachycardia.
Stoelting RK & Hillier SC. Pharmacology and Physiology in
Anesthetic Practice. 4th ed. Philadelphia, PA: Lippincott
Williams & Wilkins; 2006: 510.
Protamine can potentially stimulate the release of
thromboxane and serotonin. What are the side
effects seen if this occurs?
Pulmonary vasoconstriction, bronchoconstriction, pulmonary
hypertension, and arterial hypoxemia.
Stoelting RK & Hillier SC. Pharmacology and Physiology in
Anesthetic Practice. 4th ed. Philadelphia, PA: Lippincott
Williams & Wilkins; 2006: 510.
How do heparin and the low molecular weight
heparins (enoxeparin and dalteparin) compare with
respect to their protein binding ability? What
pharmacokinetic effect does this have?
Heparin is highly protein-bound and binds to numerous types of
protein, the concentrations of which can vary widely among
patients. This results in a wide variance in the dose-response
relationship between patients. The low molecular weight
heparins do not bind as avidly to plasma proteins. As a result,
they have a much more stable dose-response profile.
Stoelting RK & Hillier SC. Pharmacology and Physiology in
Anesthetic Practice. 4th ed. Philadelphia, PA: Lippincott
Williams & Wilkins; 2006: 511.
How does the half-life of low molecular weight
heparin compare to that of heparin?
Low molecular weight heparins have a half life of 4-5 hours
compared to about 1 hour for heparin.
Stoelting RK & Hillier SC. Pharmacology and Physiology in
Anesthetic Practice. 4th ed. Philadelphia, PA: Lippincott
Williams & Wilkins; 2006: 511.
A patient on warfarin is undergoing a preoperative
evaluation for major surgery. How long prior to
surgery should they discontinue their warfarin?
Warfarin should be discontinued 1-3 days prior to major surgery
so that the PT can return to within 20% of its normal value.
Stoelting RK & Hillier SC. Pharmacology and Physiology in
Anesthetic Practice. 4th ed. Philadelphia, PA: Lippincott
Williams & Wilkins; 2006: 513.
