Interactions with herbs
Ginkgo Biloba
  Interactions with supplements
Look Up > Drugs > Heparin
U.S. Brand Names
Generic Available
Pharmacological Index
Pregnancy Risk Factor
Adverse Reactions
Drug Interactions
Mechanism of Action
Usual Dosage
Monitoring Parameters
Reference Range
Test Interactions
Cardiovascular Considerations
Mental Health: Effects on Mental Status
Mental Health: Effects on Psychiatric Treatment
Dental Health: Local Anesthetic/Vasoconstrictor Precautions
Dental Health: Effects on Dental Treatment
Patient Information
Nursing Implications
Dosage Forms

(HEP a rin)

U.S. Brand Names

Generic Available


Heparin Calcium; Heparin Lock Flush; Heparin Sodium

Pharmacological Index



Prophylaxis and treatment of thromboembolic disorders

Pregnancy Risk Factor



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

Adverse Reactions

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, purpura, eczema

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 therapy effect)

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.

Drug Interactions

Cephalosporins which contain the MTT side chain may increase the risk of hemorrhage.

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 nitroglycerin dosages.

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 hypercoagulability.

Other drugs reported to increase heparin's anticoagulant effect include antihistamines, tetracycline, quinine, nicotine, and cardiac glycosides (digoxin).


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

Mechanism of Action

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 minutes

Absorption: Oral, rectal, I.M.: Erratic at best from all these routes of administration; S.C. absorption is also erratic, but considered acceptable for prophylactic use

Distribution: Does not cross placenta; does not appear in breast milk

Metabolism: Hepatic; believed to be partially metabolized in the reticuloendothelial system

Half-life: Mean: 1.5 hours; Range: 1-2 hours; affected by obesity, renal function, hepatic function, malignancy, presence of pulmonary embolism, and infections

Elimination: Renal, small amount excreted unchanged in urine

Usual Dosage

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 hours

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 doses.

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 dose.

Monitoring Parameters

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

Reference Range

Heparin: 0.3-0.5 unit/mL; APTT: 1.5-2.5 times the patient's baseline

Test Interactions

thyroxine (S) (competitive protein binding methods); PT, PTT, bleeding time

Cardiovascular Considerations

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 thrombocytopenia (HIT).

Mental Health: Effects on Mental Status

None reported

Mental Health: Effects on Psychiatric Treatment

None reported

Dental Health: Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Dental Health: Effects on Dental Treatment

Heparin, being a potent antithrombin agent, has caused bleeding from the gums.

Patient Information

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.

Nursing Implications

Do not administer I.M. due to pain, irritation, and hematoma formation

Dosage Forms

Heparin sodium:

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 mL)

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 (250 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)

Heparin calcium:

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)


Andrew M, Marzinotto V, Massicotte P, et al, "Heparin Therapy in Pediatric Patients: A Prospective Cohort Study," Pediatr Res, 1994, 35(1):78-83.

Aull L, Chao H, and Coy K, "Heparin-Induced Hyperkalemia," DICP, 1990, 24(3):244-6.

Becker PS and Miller VT, "Heparin-Induced Thrombocytopenia," Stroke, 1989, 20(11):1449-59.

Bern MM, Lokich JJ, Wallach, et al, "Very Low Doses of Warfarin Can Prevent Thrombosis in Central Venous Catheters. A Randomized Prospective Trial," Ann Intern Med, 1990, 112(6):423-8.

Bohannon AD and Lyles KW, "Drug-Induced Bone Disease," Clin Geriatr Med, 1994, 10(4):611-23.

Boon DM, Kappers-Klunne MC, Michiels JJ, et al, "Heparin-Induced Thrombocytopenia and Thrombosis: A Potential Fatal Complication in a Routine Treatment," Neth J Med, 1995, 46(3):146-52.

Bouvier JL, Lefevre P, Villain P, et al, "Treatment of Serious Heparin-Induced Thrombocytopenia by Plasma Exchange: Report on 4 Cases," Thromb Res, 1988, 51(3):335-6.

Bull BS, Korpman RA, Huse WM, et al, "Heparin Therapy During Extracorporeal Circulation. I. Problems Inherent in Existing Heparin Protocols," J Thorac Cardiovasc Surg, 1975, 69(5):674-84.

Carter BL, "Therapy of Acute Thromboembolism With Heparin and Warfarin," Clin Pharm, 1991, 10(7):503-18.

Chamberlin JR, Lewis B, Leya F, et al, "Successful Treatment of Heparin-Associated Thrombocytopenia and Thrombosis Using Hirulog," Can J Cardiol, 1995, 11(6):511-4.

Daghistani D, Horn M, Rodriguez Z, et al, "Prevention of Indwelling Central Venous Catheter Sepsis," Med Pediatr Oncol, 1996, 26(6):405-8.

Ginsberg JS and Hirsh J, "Optimum Use of Anticoagulants in Pregnancy," Drugs, 1988, 36(4):505-12.

Gyr P, Burroughs T, Smith K, et al, "Double Blind Comparison of Heparin and Saline Flush Solutions in Maintenance of Peripheral Infusion Devices," Pediatr Nurs, 1995, 21(4):383-9, 366.

Hirsh J, Warkentin TE, Raschke R, et al, "Heparin and Low-Molecular Weight-Heparin: Mechanisms of Action, Pharmacokinetics, Dosing Considerations, Monitoring, Efficacy and Safety," Chest, 1998, 114(5 Suppl):489S-510S.

Hollenberg GM and Van Zandt TF, "Breast and Chest Wall Hemorrhage After Routine Mammography in a Patient Receiving Heparin," Radiology, 1995, 195(2):576.

Hurtubise MR, Bottino JC, Lawson M, et al, "Restoring Patency of Occluded Central Venous Catheters," Arch Surg, 1980, 115(2):212-3.

Jick H, Slone D, Borda IT, et al, "Efficacy and Toxicity of Heparin in Relation to Age and Sex," N Engl J Med, 1968, 279(6):284-6.

Lee HN, Cook DJ, Sarabia A, et al, "Inadequacy of Intravenous Heparin Therapy in the Initial Management of Venous Thromboembolism," J Gen Intern Med, 1995, 10(6):342-5.

Mayo DJ, Horne MK 3rd, Summers BL, et al, "The Effects of Heparin Flush on Patency of the Groshong Catheter: A Pilot Study," Oncol Nurs Forum, 1996, 23(9):1401-5.

Michelson AD, Bovill E, Monagle P, et al, "Antithrombotic Therapy in Children," Chest, 1998, 114(5 Suppl):748S-69S.

Raschke RA, Reilly BM, Guidry JR, et al, "The Weight-Based Heparin Dosing Nomogram Compared With a "Standard Care" Nomogram: A Randomized Controlled Trial," Ann Intern Med, 1993, 119(9):874-81.

Scheffold N, Greinacher A, and Cyran J, "Intracardial Thrombus Formation in Heparin-Associated Thrombocytopenia Type II," Dtsch Med Wochenschr, 1995, 120(15):519-22.

Schreiner RL, Wynn RJ, and McNulty C, "Accidental Heparin Toxicity in the Newborn Intensive Care Unit," J Pediatr, 1978, 92(1):115-6.

Ulrick PJ and Manoharan A, "Heparin-Induced Skin Reaction," Med J Aust, 1984, 140(5):287-9.

Wagenknecht LE, Furberg CD, Hammon JW, et al, "Surgical Bleeding: Unexpected Effect of a Calcium Antagonist," BMJ, 1995, 310(6982):776-7.

Warkentin TE, Levine MN, Hirsch J, et al, "Heparin-Induced Thrombocytopenia in Patients Treated With Low-Molecular Weight Heparin or Unfractionated Heparin," N Engl J Med, 1995, 332(20):1330-5.

Wessler S and Gitel SN, "Pharmacology of Heparin and Warfarin," J Am Coll Cardiol, 1986, 8(6 Suppl B):10B-20B.

Wheeler A and Rubenstein EB, "Current Management of Disseminated Intravascular Coagulation," Oncology, 1994, 8(9):69-73.

Wittkowsky AK and Kino KJ, "Heparin Monitoring in Acute Thrombosis Associated With Antiphospholipid Antibody Syndrome," Pharmacotherapy, 1995, 15(4):517-21.

Copyright © 1978-2000 Lexi-Comp Inc. All Rights Reserved