heparin

Heparin is a natural anticoagulant compound in the body that prevents the formation of blood clots (thrombosis). Heparin used as medication is commercially prepared from animal mucous tissue such as ox lungs and pig intestines. Heparin is administered intravenously or subcutaneously to prevent and treat clot formation in patients who are at high risk for blood clots. Heparin inhibits the blood reactions that lead to formation of blood clots.

Blood coagulation and the resolution of blood clot are delicately balanced dynamic processes in the body. Blood contains specialized proteins known as coagulation factors that regulate the clotting process to form clots to prevent excessive bleeding from an injury and to resolve the clot once the bleeding is plugged. Some conditions can lead to formation of clots that obstruct blood vessels and block blood supply to organs. Heparin is used in the prevention and treatment of such clot formation.

Heparin works by activating antithrombin III, a factor that inhibits coagulation, thereby inhibiting the activation of the coagulation factors involved in the clotting process, particularly Xa and IIa. Heparin also inhibits the conversion of fibrinogen to fibrin, a fibrous insoluble protein that adheres to the clumped platelets to form a stable clot. Heparin can inhibit the coagulation factors that activate the clotting process, but cannot break up a clot that has already formed.

Heparin is FDA-approved for use as an anticoagulant in the following conditions:

• Prophylaxis and treatment of venous thromboembolism and pulmonary embolism
• Atrial fibrillation with embolization
• Treatment of acute and chronic consumptive coagulation disorders such as disseminated intravascular coagulation (DIC)
• Prevention of clotting in arterial and cardiac surgery
• Prophylaxis and treatment of peripheral arterial embolism
• Anticoagulant use in:
  • Blood transfusions
  • Extracorporeal circulation
  • Dialysis procedures

Off-label uses include:

• Antibiotic lock technique, adjunctive therapy (to prevent/treat catheter-related infection)
• Mechanical heart valve, bridging anticoagulation (for interruptions in warfarin therapy)
• Mechanical heart valve, postsurgical management (to transition to warfarin)
• Non-ST-elevation acute coronary syndromes
• Percutaneous coronary intervention
• Acute peripheral arterial occlusion
• ST-elevation myocardial infarction
• Catheter lock flush to prevent clot formation in the catheter

• Do not administer heparin to patients with the following conditions:
  • Known hypersensitivity to heparin or pork products
  • History of heparin-induced thrombocytopenia (HIT) and heparin-induced thrombocytopenia and thrombosis (HITT)
  • Uncontrolled active bleeding, except when this is due to disseminated intravascular coagulation
  • Conditions in which suitable blood coagulation tests such as the whole blood clotting time and partial thromboplastin time cannot be performed at appropriate intervals (required for full-dose heparin, usually not needed for low-dose heparin)
  • Cases in which the administration of sodium or chloride could be clinically detrimental (large volume heparin 2 unit/mL IV solutions only)
• Use heparin with caution in conditions with risk for hemorrhage, including:
  • Subacute bacterial endocarditis
  • Blood disorders
  • Major surgery
  • Dissecting aneurysm
  • Spinal anesthesia
  • Hemophilia
  • Abnormally heavy or prolonged menstrual bleeding (menorrhagia)
  • Gastrointestinal ulcerative lesions
  • Liver disease
  • Impaired biological stability (homeostasis)
• Hemorrhage can occur anywhere in the body of patients on heparin therapy. Higher incidence reported in women over 60 years. Unexplained fall in hematocrit, blood pressure or other symptoms may indicate hemorrhage.
• Do not use heparin meant for injection as a catheter lock-flush product. Exercise great caution before administering heparin. Medication errors can cause fatal hemorrhage.
• Thrombocytopenia can occur 2 to 20 days after start of heparin therapy with the reported incidence of up to 30% of patients. Monitor closely and discontinue heparin if platelet count falls below 100,000/cubic mm.
• Heparin-induced thrombocytopenia is a serious antibody-mediated reaction and can progress to heparin-induced thrombocytopenia and thrombosis which can cause serious thromboembolic events. Monitor patient closely for thrombocytopenia and if platelet count falls below 100,000/cubic mm, discontinue heparin.
• When using full dose heparin, adjust dosage based on frequent coagulation tests. Discontinue heparin if clotting time is significantly prolonged or hemorrhage occurs.
• Monitor patients for development of heparin resistance.
• Heparin can suppress adrenal secretion of aldosterone and lead to hyperkalemia, particularly in patients with conditions such as diabetes, metabolic acidosis or chronic kidney failure. Evaluate potassium levels before starting and periodically during heparin therapy.
• Monitor patients for hypersensitivity reactions.
• Do not administer products preserved with benzyl alcohol to newborn or young babies, pregnant or breastfeeding women. Can cause serious life-threatening reaction known as gasping syndrome in the baby.
• Some preparations may contain sulfite which may cause allergic reactions.

• Common side effects of heparin include:
  • Hemorrhage that may include:
    • Gastrointestinal tract bleeding
    • Urinary tract bleeding
    • Adrenal bleeding with resultant adrenal insufficiency
    • Ovarian hemorrhage
    • Retroperitoneal hemorrhage
• Heparin-induced thrombocytopenia
• Heparin-induced thrombocytopenia and thrombosis, which can cause:
  • Deep vein thrombosis
  • Pulmonary embolism
  • Cerebral vein thrombosis
  • Reduced blood supply to the limbs (limb ischemia) and limb pain
  • Stroke
  • Heart attack (myocardial infarction)
  • Thrombosis in cardiac prosthetic valve
  • Skin tissue death (necrosis)
  • Gangrene of the extremities
• Thrombocytopenia
• Bruising
• Blood vessel spasm (vasospasm)
• Heparin resistance
• Hypersensitivity reactions including:
  • Chills
  • Fever
  • Hives (urticaria)
  • Asthma
  • Nasal inflammation (rhinitis)
  • Watering eyes (lacrimation)
  • Headache
  • Nausea
  • Vomiting
  • Itching and burning of the soles of feet
  • Severe allergic reactions (anaphylaxis)
  • Anaphylactic shock
• Elevation of liver enzymes ALT and AST
• Injection site reactions that include:
  • Irritation and pain
  • Skin ulceration
  • Redness (erythema)
  • Hematoma
  • Tissue death (necrosis)
• Hair loss (alopecia)
• Painful and prolonged erection (priapism)
• Bone loss (osteoporosis) with long-term use
• High blood potassium levels (hyperkalemia)
• Risk of serious adverse reactions in infants due to benzyl alcohol
• Rebound increase in blood fats (hyperlipemia) upon discontinuation of heparin

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Adult:

Heparin Lock Solution

• 1 unit/mL
• 2 units/mL
• 10 units/mL
• 100 units/mL

Injectable Solution

• 1000 units/mL
• 2500 units/mL
• 5000 units/mL
• 10,000 units/mL
• 20,000 units/mL

Premixed IV Solution

• 12,500 units/250mL
• 20,000 units/500mL
• 25,000 units/250mL
• 25,000 units/500mL

Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE)

Prophylaxis

• 5,000 units subcutaneously (SC) every 8-12 hours, or
• 7,500 units subcutaneously every 12 hours

Treatment

• 80 units/kg intravenous (IV) bolus, then continuous infusion of 18 units/kg/hour, or
• 5000 units intravenous bolus, then continuous infusion of 1300 units/hour, or
• 250 units/kg (alternatively, 17,500 units) subcutaneously, then 250 units/kg every 12 hours

Dosing considerations

• Numerous concentrations available; extreme caution is required to avoid medication error

Acute Coronary Syndromes

Percutaneous coronary intervention (PCI)

• Without GPIIb/IIIa inhibitor: Initial IV bolus of 70-100 units/kg (target ACT 250-300 sec)  
• With GPIIb/IIIa inhibitor: Initial IV bolus of 50-70 units/kg (target ACT over 200 sec)

ST-Elevation Myocardial Infarction (STEMI)

• Patient on fibrinolytics: IV bolus of 60 units/kg (max: 4000 units), THEN 12 units/kg/hour (max 1000 units/hour) as continuous IV infusion
• Dose should be adjusted to maintain activated partial thromboplastin time (aPTT) of 50-70 sec

Unstable Angina/NSTEMI

• Initial IV bolus of 60-70 units/kg (max: 5000 units), THEN initial IV infusion of 12-15 units/kg/hour (max: 1000 units/hour)
• Dose should be adjusted to maintain aPTT of 50-70 sec

Dosing considerations

• Numerous concentrations available; extreme caution is required to avoid medication error

Anticoagulation

Intermittent IV injection

• 8000-10,000 units IV initially, THEN 50-70 units/kg (5000-10,000 units) every 4 to 6 hours  

Continuous IV infusion

• 5000 units IV injection, followed by continuous IV infusion of 20,000-40,000 units/every 24 hours

Dosing considerations

• Numerous concentrations available; extreme caution is required to avoid medication error
• Heparin sodium may prolong one-stage prothrombin time; when heparin sodium is given with dicumarol or warfarin sodium, a period of at least 5 hours after last intravenous dose or 24 hours after last subcutaneous dose should elapse before blood is drawn if a valid prothrombin time is to be obtained

Catheter Patency

• Prevention of clot formation within venous and arterial catheters
• Use 100 units/mL; instill enough volume to fill lumen of catheter

Dosing considerations

• Numerous concentrations available; extreme caution is required to avoid medication error
• Amount and frequency depend on catheter volume and type
• Peripheral heparin locks typically are flushed every 6 to 8 hours  

Dosing Modifications

• Hepatic impairment: Caution is advised; dosage adjustment may be required

Pediatric:

Heparin Lock Solution

• 10 units/mL
• 100 units/mL

Injectable Solution

• 1000 units/mL
• 5000 units/mL
• 10,000 units/mL

Venous Thromboembolic Prophylaxis (Off-label)

• 100-150 units/kg IV once

Venous Thromboembolic Treatment (Off-label)

Children younger than 1 year

• Loading dose of 75 units/kg IV, THEN 28 units/kg/hour IV as initial maintenance dose  

Children older than 1 year

• Loading dose of 75 units/kg IV, THEN 20 units/kg/hour IV as initial maintenance dose

Intermittent IV injection

• Initially give 50-100 units/kg IV infusion, THEN 100 units/kg IV infusion every 4 hours as a maintenance dose

Catheter Patency (Off-label)

• Initially give 50-100 units/kg IV infusion, THEN 100 units/kg IV infusion every 4 hours as maintenance dose  
• Infants under 10 kg: 10 units/mL; instill enough volume to fill lumen of catheter
• Children and infants over 10 kg: 10-100 units/mL; instill enough volume to fill lumen of catheter

Dosing Considerations

• Numerous concentrations available; extreme caution is required to avoid medication error
• When prescribing in infants, consider combined daily metabolic load of benzyl alcohol from all sources including heparin sodium injection (contains 9.45 mg of benzyl alcohol) and other drugs containing benzyl alcohol; the minimum amount of benzyl alcohol at which serious adverse reactions may occur is not known
• There are no adequate, well-controlled studies on heparin use in pediatric patients; pediatric dosing recommendations are based on clinical experience
• Use preservative-free heparin in neonates and infants; benzyl alcohol preservative has been associated with serious adverse effects (ie, gasping syndrome, which is characterized by central nervous system depression, metabolic acidosis, and gasping respirations) and death in pediatric patients

Venous thromboembolic treatment (off-label)

• Adjust heparin dose based on desired aPTT

Catheter patency (off-label)

• Dosage amount and frequency depend on catheter volume and type
• Peripheral heparin locks typically are flushed every 6 to 8 hours

• Heparin overdose may result in severe bleeding. Heparin effects may be reversed with slow infusion of protamine sulfate (1% solution).
• No more than 50 mg should be administered, very slowly, in any 10 minute period.
• Each milligram of protamine sulfate neutralizes approximately 100 USP units of heparin. The amount of protamine required decreases over time as heparin is metabolized.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Severe Interactions of Heparin include:
  • corticorelin
  • defibrotide
  • mifepristone
  • prothrombin complex concentrate, human
• Heparin has serious interactions with at least 65 different drugs.
• Heparin has moderate interactions with at least 146 different drugs.
• Heparin has mild interactions with at least 22 different drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• Published reports on heparin use during pregnancy did not show evidence of fetal or maternal bleeding or other complications.
• The risk of thromboembolism increases during pregnancy and immediately after delivery, due to pregnancy-induced physiologic changes.
• Pregnant patients who have mechanical heart valves have a higher risk for adverse maternal and fetal outcomes, particularly without appropriate anticoagulation treatment.
• Heparin may be used for anticoagulation during pregnancy, and low molecular weight heparin is generally preferred over unfractionated heparin in pregnancy.
• Due to its large molecular weight, heparin is not likely to be excreted in human milk, and any heparin in milk would not be orally absorbed by a breastfed infant.
• Heparin use is compatible with breastfeeding, however, preservative-free products are recommended because some products contain benzyl alcohol as a preservative, which can cause serious adverse reactions in the infant.

• Heparin can make you bruise or bleed more easily and take longer to stop bleeding. If you notice any unusual bruising or bleeding, report to your physician immediately.
• If you are on heparin therapy, you must inform your dentist or physician before any procedure that can cause bleeding.
• Some heparin reactions can occur up to several weeks after discontinuing heparin. Notify your physician if you observe any unusual symptoms.