Heparin Calcium; Heparin Lock Flush; Heparin Sodium|
Prophylaxis and treatment of thromboembolic disorders
Hypersensitivity to heparin or any component; severe thrombocytopenia;
uncontrolled active bleeding except when due to DIC; suspected intracranial
hemorrhage; not for I.M. use; not for use when appropriate monitoring parameters
cannot be obtained
Use cautiously in patients with a documented hypersensitivity reaction and
only in life-threatening situations. Hemorrhage is the most common complication.
Monitor for signs and symptoms of bleeding. Certain patients are at increased
risk of bleeding. Risk factors include bacterial endocarditis; congenital or
acquired bleeding disorders; active ulcerative or angiodysplastic GI diseases;
severe uncontrolled hypertension; hemorrhagic stroke; or use shortly after
brain, spinal, or ophthalmology surgery; patient treated concomitantly with
platelet inhibitors; conditions associated with increased bleeding tendencies
(hemophilia, vascular purpura); recent GI bleeding; thrombocytopenia or platelet
defects; severe liver disease; hypertensive or diabetic retinopathy; or in
patients undergoing invasive procedures. A higher incidence of bleeding has been
reported in patients >60 years of age, particularly women. They are also more
sensitive to the dose.
Some preparations contain benzyl alcohol as a preservative. In neonates,
large amounts of benzyl alcohol (>100 mg/kg/day) have been associated with
fatal toxicity (gasping syndrome). The use of preservative-free heparin is,
therefore, recommended in neonates. Some preparations contain sulfite which may
cause allergic reactions.
Heparin does not possess fibrinolytic activity and, therefore, cannot lyse
established thrombi; discontinue heparin if hemorrhage occurs; severe hemorrhage
or overdosage may require protamine
As with all anticoagulants, bleeding is the major adverse effect of heparin.
Hemorrhage may occur at virtually any site. Risk is dependent on multiple
variables, including the intensity of anticoagulation and patient
susceptibility. Additional adverse effects are often related to idiosyncratic
reactions, and the frequency is difficult to estimate.
Central nervous system: Fever, headache, chills
Dermatologic: Unexplained bruising, urticaria, alopecia, dysesthesia pedis,
Endocrine and Metabolic: Hyperkalemia (supression of aldosterone), rebound
hyperlipidemia on discontinuation
Gastrointestinal: Nausea, vomiting, constipation, hematemesis
Genitourinary: Frequent or persistent erection
Hematologic: Hemorrhage, blood in urine, bleeding from gums, epistaxis,
adrenal hemorrhage, ovarian hemorrhage, retroperitoneal hemorrhage,
thrombocytopenia (see note)
Hepatic: Elevated liver enzymes (AST/ALT) Local: Irritation, ulceration,
cutaneous necrosis have been rarely reported with deep S.C. injections, I.M.
injection (not recommended) is associated with a high incidence of these effects
Neuromuscular & skeletal: Peripheral neuropathy, osteoporosis (chronic
Respiratory: Hemoptysis, pulmonary hemorrhage, asthma, rhinitis
Ocular: Conjunctivitis (allergic reaction)
Miscellaneous: Allergic reactions, anaphylactoid reactions
Note: Thrombocytopenia has been reported to occur at an incidence
between 0% and 30%. It is often of no clinical significance. However,
immunologically mediated heparin-induced thrombocytopenia has been estimated to
occur in 1% to 2% of patients, and is marked by a progressive fall in platelet
counts and, in some cases, thromboembolic complications (skin necrosis,
pulmonary embolism, gangrene of the extremities, stroke or myocardial
infarction); daily platelet counts for 5-7 days at initiation of therapy may
help detect the onset of this complication.
Case reports: Bronchospasm, erythematous plaques
The primary symptom of overdose is bleeding
Antidote is protamine; dose 1 mg per 1 mg (100 units) of heparin. Discontinue
all heparin if evidence of progressive immune thrombocytopenia occurs.
Cephalosporins which contain the MTT side chain may increase the risk of
Drugs which affect platelet function (eg, aspirin, NSAIDs, dipyridamole,
ticlopidine, clopidogrel) may potentiate the risk of hemorrhage.
Nitroglycerin (I.V.) may decrease heparin's anticoagulant effect. This
interaction has not been validated in some studies, and may only occur at high
Penicillins (parenteral) may prolong bleeding time via inhibition of platelet
aggregation, potentially increasing the risk of hemorrhage.
Thrombolytic agents increase the risk of hemorrhage.
Warfarin: Risk of bleeding may be increased during concurrent therapy.
Heparin is commonly continued during the initiation of warfarin therapy to
assure anticoagulation and to protect against possible transient
Other drugs reported to increase heparin's anticoagulant effect include
antihistamines, tetracycline, quinine, nicotine, and cardiac glycosides
Heparin solutions are colorless to slightly yellow; minor color variations do
not affect therapeutic efficacy
Heparin should be stored at controlled room temperature and protected from
freezing and temperatures >40°C
Stability at room temperature and refrigeration:
Prepared bag: 24 hours
Premixed bag: After seal is broken 4 days
Out of overwrap stability: 30 days
Standard diluent: 25,000 units/500 mL D5W (premixed)
Minimum volume: 250 mL D5W
Potentiates the action of antithrombin III and thereby inactivates thrombin
(as well as activated coagulation factors IX, X, XI, XII, and plasmin) and
prevents the conversion of fibrinogen to fibrin; heparin also stimulates release
of lipoprotein lipase (lipoprotein lipase hydrolyzes triglycerides to glycerol
and free fatty acids)
Onset of anticoagulation: I.V.: Immediate with use; S.C.: Within 20-30
Absorption: Oral, rectal, I.M.: Erratic at best from all these routes of
administration; S.C. absorption is also erratic, but considered acceptable for
Distribution: Does not cross placenta; does not appear in breast milk
Metabolism: Hepatic; believed to be partially metabolized in the
Half-life: Mean: 1.5 hours; Range: 1-2 hours; affected by obesity, renal
function, hepatic function, malignancy, presence of pulmonary embolism, and
Elimination: Renal, small amount excreted unchanged in urine
Line flushing: When using daily flushes of heparin to maintain patency of
single and double lumen central catheters, 10 units/mL is commonly used for
younger infants (eg, <10 kg) while 100 units/mL is used for older infants,
children, and adults. Capped PVC catheters and peripheral heparin locks require
flushing more frequently (eg, every 6-8 hours). Volume of heparin flush is
usually similar to volume of catheter (or slightly greater). Additional flushes
should be given when stagnant blood is observed in catheter, after catheter is
used for drug or blood administration, and after blood withdrawal from catheter.
Addition of heparin (0.5-1 unit/mL) to peripheral and central TPN has been
shown to increase duration of line patency. The final concentration of heparin
used for TPN solutions may need to be decreased to 0.5 units/mL in small infants
receiving larger amounts of volume in order to avoid approaching therapeutic
amounts. Arterial lines are heparinized with a final concentration of 1 unit/mL.
Intermittent I.V.: Initial: 50-100 units/kg, then 50-100 units/kg every 4
I.V. infusion: Initial: 50 units/kg, then 15-25 units/kg/hour; increase dose
by 2-4 units/kg/hour every 6-8 hours as required
Prophylaxis (low-dose heparin): S.C.: 5000 units every 8-12 hours
Intermittent I.V.: Initial: 10,000 units, then 50-70 units/kg (5000-10,000
units) every 4-6 hours
I.V. infusion: 50 units/kg to start, then 15-25 units/kg/hour as continuous
infusion; increase dose by 5 units/kg/hour every 4 hours as required according
to PTT results, usual range: 10-30 units/hour
Weight-based protocol: 80 units/kg I.V. push followed by continuous infusion
of 18 units/kg/hour. Using a Standard Heparin Solution (25,000 units/500mL
D5W), the following infusion rates can be used to achieve the listed
For a dose of:
400 units/hour: Infuse at 8 mL/hour
500 units/hour: Infuse at 10 mL/hour
600 units/hour: Infuse at 12 mL/hour
700 units/hour: Infuse at 14 mL/hour
800 units/hour: Infuse at 16 mL/hour
900 units/hour: Infuse at 18 mL/hour
1000 units/hour: Infuse at 20 mL/hour
1100 units/hour: Infuse at 22 mL/hour
1200 units/hour: Infuse at 24 mL/hour
1300 units/hour: Infuse at 26 mL/hour
1400 units/hour: Infuse at 28 mL/hour
1500 units/hour: Infuse at 30 mL/hour
1600 units/hour: Infuse at 32 mL/hour
1700 units/hour: Infuse at 34 mL/hour
1800 units/hour: Infuse at 36 mL/hour
1900 units/hour: Infuse at 38 mL/hour
2000 units/hour: Infuse at 40 mL/hour
Dosing adjustments in the elderly: May be more sensitive to a given
Platelet counts, PTT, hemoglobin, hematocrit, signs of bleeding
Note: Continuous I.V. infusion is preferred vs I.V. intermittent
injections. For full-dose heparin (ie, nonlow-dose), the dose should be titrated
according to PTT results. For anticoagulation, an APTT 1.5-2.5 times normal is
usually desired. APTT is usually measured prior to heparin therapy, 6-8 hours
after initiation of a continuous infusion (following a loading dose), and 6-8
hours after changes in the infusion rate; increase or decrease infusion by 2-4
units/kg/hour dependent on PTT.
Heparin Infusion Dose Adjustment:
APTT >3x control: Decrease infusion rate 50%
APTT 2-3x control: Decrease infusion rate 25%
APTT 1.5-2x control: No change
APTT <1.5x control: Increase rate of infusion 25%; max 2500 units/hour
Heparin: 0.3-0.5 unit/mL; APTT: 1.5-2.5 times the patient's
(competitive protein binding
Heparin is routinely used in acute coronary syndromes to inhibit clot
formation. Heparin therapy is commonly combined with thrombolytic and other
antithrombotic therapy to decrease the risk of clot formation. A patient's
activated partial thromboplastin time (aPTT) should be monitored at baseline and
every 6 hours and maintained in the therapeutic range of 1.5-2 times control.
Daily platelet counts may help in early identification of heparin-induced
|Mental Health: Effects
on Mental Status|
Effects on Psychiatric
|Dental Health: Local
No information available to require special precautions
Effects on Dental Treatment|
Heparin, being a potent antithrombin agent, has caused bleeding from the
This drug can only be administered by injection. You may have a tendency to
bleed easily while taking this drug; brush teeth with soft brush, floss with
waxed floss, use electric razor, avoid scissors or sharp knives, and potentially
harmful activities. May discolor urine or stool. Report CNS changes (fever,
confusion), unusual fever, persistent nausea or GI upset, unusual bleeding or
bruising (bleeding gums, nosebleed, blood in urine, dark stool), pain in joints
or back, swelling or pain at injection site. Pregnancy precautions:
Inform prescriber if you are pregnant.
Do not administer I.M. due to pain, irritation, and hematoma
Lock flush injection:
Beef lung source: 10 units/mL (1 mL, 2 mL, 2.5 mL, 3 mL, 5 mL, 10 mL, 30 mL);
100 units/mL (1 mL, 2 mL, 2.5 mL, 3 mL, 5 mL, 10 mL, 30 mL)
Porcine intestinal mucosa source: 10 units/mL (1 mL, 2 mL, 10 mL, 30 mL); 100
units/mL (1 mL, 2 mL, 10 mL, 30 mL)
Porcine intestinal mucosa source, preservative free: 10 units/mL (1 mL); 100
units/mL (1 mL)
Multiple-dose vial injection:
Beef lung source, with preservative: 1000 units/mL (5 mL, 10 mL, 30 mL); 5000
units/mL (10 mL); 10,000 units/mL (4 mL, 5 mL, 10 mL); 20,000 units/mL (2 mL, 5
mL, 10 mL); 40,000 units/mL (5 mL)
Porcine intestinal mucosa source, with preservative: 1000 units/mL (10 mL, 30
mL); 5000 units/mL (10 mL); 10,000 units/mL (4 mL); 20,000 units/mL (2 mL, 5 mL)
Single-dose vial injection:
Beef lung source: 1000 units/mL (1 mL); 5000 units/mL (1 mL); 10,000 units/mL
(1 mL); 20,000 units/mL (1 mL); 40,000 units/mL (1 mL)
Porcine intestinal mucosa: 1000 units/mL (1 mL); 5000 units/mL (1 mL); 10,000
units/mL (1 mL); 20,000 units/mL (1 mL); 40,000 units/mL (1 mL)
Unit dose injection:
Porcine intestinal mucosa source, with preservative: 1000 units/dose (1 mL, 2
mL); 2500 units/dose (1 mL); 5000 units/dose (0.5 mL, 1 mL); 7500 units/dose (1
mL); 10,000 units/dose (1 mL); 15,000 units/dose (1 mL); 20,000 units/dose (1
Heparin sodium infusion, porcine intestinal mucosa source:
D5W: 40 units/mL (500 mL); 50 units/mL (250 mL, 500 mL); 100
units/mL (100 mL, 250 mL)
NaCl 0.45%: 2 units/mL (500 mL, 1000 mL); 50 units/mL (250 mL); 100 units/mL
NaCl 0.9%: 2 units/mL (500 mL, 1000 mL); 5 units/mL (1000 mL); 50 units/mL
(250 mL, 500 mL, 1000 mL)
Unit dose injection, porcine intestinal mucosa, preservative free
(Calciparine®): 5000 units/dose (0.2 mL); 12,500
units/dose (0.5 mL); 20,000 units/dose (0.8 mL)
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