Side effect of heparin

Heparin Injection

Medically reviewed by Kaci Durbin, MD Last updated on Jan 6, 2020.

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What is heparin injection?

Heparin is an anticoagulant (blood thinner) that prevents the formation of blood clots.

Heparin is used to treat and prevent blood clots caused by certain medical conditions or medical procedures. It is also used before surgery to reduce the risk of blood clots.

Do not use heparin injection to flush (clean out) an intravenous (IV) catheter. A separate product is available to use as catheter lock flush. Using the wrong type of heparin to flush a catheter can result in fatal bleeding.

Important Information

Do not use heparin injection to flush (clean out) an intravenous (IV) catheter, or fatal bleeding could result. A separate product is available to use as catheter lock flush.

You should not use heparin if you have uncontrolled bleeding or a severe lack of platelets in your blood. Do not use this medicine if you have ever been diagnosed with “heparin-induced thrombocytopenia,” or low platelets caused by heparin or pentosan polysulfate.

Heparin increases your risk of bleeding, which can be severe or life-threatening. You will need frequent tests to measure your blood-clotting time.

Call your doctor or seek emergency medical attention if you have unusual bleeding or bruising, severe stomach or back pain, unusual tiredness, a nosebleed, blood in your urine or stools, coughing up blood, or any bleeding that will not stop.

Heparin can cause you to have bleeding episodes while you are using it and for several weeks after you stop.

Do not use heparin injection to flush (clean out) an intravenous (IV) catheter, or fatal bleeding could result. A separate product is available to use as catheter lock flush.

Before taking this medicine

You should not use this medicine if you are allergic to heparin or pork products, or if you have:

  • a history of low platelets in your blood caused by using heparin or pentosan polysulfate;

  • a severe lack of platelets in your blood; or

  • uncontrolled bleeding.

You may not be able to use heparin if you are unable to receive routine blood-clotting tests at the proper intervals during treatment.

To make sure heparin is safe for you, tell your doctor if you have ever had:

  • an infection of the lining of your heart (also called bacterial endocarditis);

  • severe or uncontrolled high blood pressure;

  • a bleeding or blood clotting disorder;

  • a stomach or intestinal disorder;

  • liver disease;

  • if you use a blood thinner (warfarin, Coumadin, Jantoven) and you have routine “INR” or prothrombin time tests; or

  • if you are having a menstrual period.

It is not known whether heparin will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant. You may need to use a form of heparin that does not contain a preservative.

You should not breastfeed while using this medicine.

How should I use heparin injection?

Heparin is injected under the skin or as an infusion into a vein. A healthcare provider will give your first dose and may teach you how to properly use the medication by yourself.

Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose. Use the medicine exactly as directed.

Read and carefully follow any Instructions for Use provided with your medicine. Ask your doctor or pharmacist if you don’t understand all instructions.

Prepare an injection only when you are ready to give it. Do not use the medicine if it has changed colors or has particles in it. Call your pharmacist for new medicine.

Do not use a prefilled syringe when giving this medicine to a child. The prefilled syringe contains more than a child’s dose of heparin.

Heparin increases your risk of bleeding, which can be severe or life-threatening. You will need frequent tests to measure your blood-clotting time. The timing of these tests is very important in helping your doctor determine whether it is safe for you to continue using this medicine.

If you need surgery, dental work, or a medical procedure, tell the care provider ahead of time that you are using heparin.

Store at room temperature away from moisture and heat.

Use a needle and syringe only once and then place them in a puncture-proof “sharps” container. Follow state or local laws about how to dispose of this container. Keep it out of the reach of children and pets.

You may be switched from injectable heparin to an oral (taken by mouth) blood thinner. Do not stop using the injection until your doctor tells you to. You may need to use both the injection and the oral forms for a short time.

What happens if I miss a dose?

Call your doctor for instructions if you miss a dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include easy bruising, nosebleeds, blood in your urine or stools, black or tarry stools, or any bleeding that will not stop.

What should I avoid while using heparin injection?

Avoid medication errors by using only the form and strength your doctor prescribes.

Ask your doctor before taking a nonsteroidal anti-inflammatory drug (NSAID). Using an NSAID with heparin may cause you to bruise or bleed easily.

Heparin injection side effects

Get emergency medical help if you have signs of an allergic reaction to heparin: nausea, vomiting, sweating, hives, itching, trouble breathing, swelling of your face, lips, tongue, or throat, or feeling like you might pass out.

Heparin may cause you to bleed more easily, which can be severe or life-threatening. You may also have bleeding on the inside of your body. Seek emergency medical attention if you have:

  • skin warmth or discoloration;

  • chest pain, irregular heartbeats;

  • shortness of breath, dizziness, anxiety, sweating;

  • any unusual bleeding or bruising;

  • severe pain or swelling in your stomach, lower back, or groin;

  • dark or blue-colored skin on your hands or feet;

  • nausea, vomiting, loss of appetite;

  • unusual tiredness;

  • any bleeding that will not stop; or

  • nosebleed, blood in your urine or stools, black or tarry stools, or coughing up blood or vomit that looks like coffee grounds.

Heparin can cause you to have bleeding episodes while you are using it and for several weeks after you stop.

Bleeding may be more likely in older adults, especially women over 60 years of age

Stop using this medicine and call your doctor at once if you have:

  • skin changes where the medicine was injected;

  • fever, chills, runny nose, or watery eyes;

  • easy bruising, unusual bleeding, purple or red spots under your skin; or

  • signs of a blood clot – sudden numbness or weakness, problems with vision or speech, swelling or redness in an arm or leg.

Common heparin side effects may include:

  • unusual bleeding or bruising;

  • uncontrolled bleeding;

  • allergic reactions; or

  • abnormal liver function tests.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect heparin injection?

Ask your doctor before taking a nonsteroidal anti-inflammatory drug (NSAID) such as aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve), celecoxib, diclofenac, indomethacin, meloxicam, and others. Using an NSAID with heparin may cause you to bruise or bleed easily.

Tell your doctor about all your other medicines, especially:

  • a blood thinner – warfarin, Coumadin, Jantoven;

  • digitalis;

  • tetracyclines;

  • nicotine; or

  • antihistamines.

This list is not complete and many other drugs may interact with heparin. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible drug interactions are listed here.

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use heparin only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Copyright 1996-2020 Cerner Multum, Inc. Version: 15.01.

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Hemorrhage is the chief complication that may result from heparin therapy (see WARNINGS). An overly prolonged clotting time or minor bleeding during therapy can usually be controlled by withdrawing the drug (see OVERDOSAGE). It should be appreciated that gastrointestinal or urinary tract bleeding during anticoagulant therapy may indicate the presence of an underlying occult lesion. Bleeding can occur at any site but certain specific hemorrhagic complications may be difficult to detect:

  1. Adrenal hemorrhage, with resultant acute adrenal insufficiency, has occurred during anticoagulant therapy. Therefore, such treatment should be discontinued in patients who develop signs and symptoms of acute adrenal hemorrhage and insufficiency. Initiation of corrective therapy should not depend on laboratory confirmation of the diagnosis since any delay in an acute situation may result in the patient’s death.
  2. Ovarian (corpus luteum) hemorrhage developed in a number of women of reproductive age receiving short- or long-term anticoagulant therapy. This complication if unrecognized may be fatal.
  3. Retroperitoneal hemorrhage.


Generalized hypersensitivity reactions have been reported with chills, fever, and urticaria as the most usual manifestations, and asthma, rhinitis, lacrimation, headache, nausea and vomiting and anaphylactoid reactions, including shock, occurring more rarely. Itching and burning, especially on the plantar site of the feet may occur.

Thrombocytopenia has been reported to occur in patients receiving heparin with a reported incidence of 0 to 30%. While often mild and of no obvious clinical significance, such thrombocytopenia can be accompanied by severe thromboembolic complications such as skin necrosis, gangrene of the extremities that may lead to amputation, myocardial infarction, pulmonary embolism, stroke and possibly death. (See WARNINGS and PRECAUTIONS.)

Certain episodes of painful, ischemic and cyanosed limbs have in the past been attributed to allergic vasospastic reactions. Whether these are in fact identical to the thrombocytopenia associated complications remains to be determined.


Osteoporosis following long-term administration of high doses of heparin, cutaneous necrosis after systemic administration, suppression of aldosterone synthesis, delayed transient alopecia, priapism and rebound hyperlipemia on discontinuation of heparin sodium have also been reported.

Significant elevations of aminotransferase (SGOT and SGPT ) levels have occurred in a high percentage of patients (and healthy subjects) who have received heparin.

Read the entire FDA prescribing information for Heparin (Heparin)

Heparin is an injectable drug used to prevent and treat blood clots in the veins, arteries, or lungs.

The medicine is in a class of drugs known as anticoagulants (blood thinners). It works by decreasing the blood’s ability to clot.

Heparin is often given to people with atrial fibrillation, deep vein thrombosis (DVT), pulmonary emboli, certain blood clotting disorders, and to bed- or wheelchair-bound people.

It’s used during dialysis, blood transfusions, and blood sampling. It’s also given before surgery to reduce the risk of blood clots.

Heparin was approved by the Food and Drug Administration (FDA) in 1939.

Heparin Warnings

Before taking heparin, tell your doctor if you have:

  • A low amount of platelets in your blood
  • Heavy bleeding anywhere in your body
  • Your menstrual period
  • A fever or infection

This medicine may cause osteoporosis, especially if it’s used for a long period of time. Talk to your doctor about this risk.

Tell your physician if you have or have ever had any of the following medical conditions before taking heparin:

  • A bleeding disorder such as hemophilia
  • Antithrombin III deficiency (a condition that causes blood clots to form)
  • Blood clots in the legs, lungs, or anywhere in the body
  • Cancer
  • A stomach or intestinal disorder
  • Unusual bruising or purple spots under the skin
  • High blood pressure
  • Bacterial endocarditis (an infection in the lining of your heart)
  • Liver disease

Also, tell your doctor if you’ve recently had a spinal tap procedure, spinal anesthesia, surgery (especially involving the brain, eye, or spinal cord), or a heart attack.

Tell your doctor or dentist you’re taking heparin before having any type of procedure.

Heparin-Induced Thrombocytopenia (HIT)

Some people experience a serious reaction to heparin, which can cause a condition known as heparin-induced thrombocytopenia (HIT).

HIT is characterized by a decrease of platelets in the blood.

Get immediate medical help if you experience any of the following side effects while taking heparin, which could be signs of HIT:

  • Chest pain
  • Trouble breathing
  • Confusion
  • Weakness on one side of the body
  • Vision changes
  • Slurred speech
  • Change in color of the arms or legs
  • Pain or loss of feeling in the arms or legs

Pregnancy and Heparin

It’s not known if Heparin could harm an unborn baby.

Still, this drug is sometimes used alone or with aspirin to prevent pregnancy loss or other problems in pregnant women.

Talk to your doctor about the risks of using heparin during pregnancy.

Don’t use this medicine while breastfeeding without first talking to your doctor.

Heparin Sodium Side Effects

Visit your healthcare professional for regular checks on your progress. You may need blood work done while you are taking this medicine. Your condition will be monitored carefully while you are receiving this medicine. It is important not to miss any appointments.

Wear a medical ID bracelet or chain, and carry a card that describes your disease and details of your medicine and dosage times.

Notify your doctor or healthcare professional at once if you have cold, blue hands or feet.

If you are going to need surgery or other procedure, tell your healthcare professional that you are using this medicine.

Avoid sports and activities that might cause injury while you are using this medicine. Severe falls or injuries can cause unseen bleeding. Be careful when using sharp tools or knives. Consider using an electric razor. Take special care brushing or flossing your teeth. Report any injuries, bruising, or red spots on the skin to your healthcare professional.

Using this medicine for a long time may weaken your bones and increase the risk of bone fractures.

You should make sure that you get enough calcium and vitamin D while you are taking this medicine. Discuss the foods you eat and the vitamins you take with your healthcare professional.

Wear a medical ID bracelet or chain. Carry a card that describes your disease and details of your medicine and dosage times.

Side Effects

Mild pain/redness/irritation at the injection site may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly. Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects. Tell your doctor right away if you have any serious side effects, including: swelling at injection site, bone pain, easily broken bones. This medication can cause bleeding if its effect on your clotting proteins is too much. Tell your doctor right away if you develop any signs of serious bleeding, including unusual pain/swelling/discomfort, prolonged bleeding from cuts or gums, persistent nosebleeds, unusually heavy/prolonged menstrual periods, unusual/easy bruising, dark urine, black stools, severe headache, unusual dizziness. Some patients can have certain bad reactions to heparin (heparin-induced thrombocytopenia-HIT or heparin-induced thrombocytopenia and thrombosis-HITT). This can occur during treatment and up to several weeks after treatment with heparin has stopped. You should not use this drug again if you have this type of reaction with heparin. Get medical help right away if you have any very serious side effects, including: pain/loss of feeling in the arms/legs, change in color of the arms/legs, chest pain, trouble breathing, confusion, weakness on one side of the body, slurred speech, vision changes. A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing. This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist. In the US – Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at In Canada – Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

  • heparin-induced thrombocytopenia
  • thrombocytopenic disorder
  • peripheral neuropathy
  • eye tearing
  • Thrombosis in Heparin-Induced Thrombocytopenia
  • hemorrhage
  • Rhinitis
  • asthma
  • bronchospastic pulmonary disease
  • renal artery thrombosis
  • genitourinary tract hemorrhage
  • priapism
  • Erythema
  • pruritus of skin
  • alopecia
  • skin ulcer
  • urticaria
  • dyschromia
  • osteoporosis
  • fever
  • chills
  • skin rash
  • headache disorder
  • dermal necrosis
  • nausea and vomiting
  • Anaphylaxis
  • hypersensitivity drug reaction
  • Injection Site Sequelae
  • Hematoma
  • Adrenal Hemorrhage
  • Ovarian Hemorrhage
  • Retroperitoneal Hemorrhage
  • paresthesia of plantar surface
  • increased alanine transaminase
  • increased aspartate transaminase

Drug Interactions

See also How to Use section. Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor’s approval. Some products that may interact with this drug include: mifepristone, oritavancin, telavancin. This medication is sometimes used together with other drugs that have “blood thinning” or anti-platelet effects such as aspirin, clopidogrel, or warfarin. If your doctor prescribes a combination of these drugs, he or she will monitor you closely to minimize your risk of bleeding. Keep all medical and laboratory appointments. Check all prescription and nonprescription medicine labels carefully since many medications contain pain relievers/fever reducers (NSAIDs such as ibuprofen, naproxen, or aspirin) that can increase the risk of bleeding when used with heparin. However, if your doctor has directed you to take low-dose aspirin to prevent heart attack or stroke (usually at dosages of 81-325 milligrams a day), you should continue taking the aspirin unless your doctor instructs you otherwise. Ask your doctor or pharmacist for more details. Cigarette smoking decreases blood levels of this medication. Tell your doctor if you smoke or if you have recently stopped smoking. This medication may interfere with certain laboratory tests (including certain liver function tests, prothrombin time), possibly causing false test results. Make sure laboratory personnel and all your doctors know you use this drug.

What is heparin injection used for?

  • Treating and preventing blood clots in the veins of the leg (deep vein thrombosis).
  • Treating and preventing blood clots travelling to the lungs (pulmonary embolism).
  • Treating blood clots in the coronary arteries in unstable angina.
  • Treating blood clots that are blocking a peripheral artery, eg in the leg (peripheral arterial occlusion).
  • Preventing further blood clots in the heart immediately following a heart attack.
  • Preventing blood from clotting when it is filtered through an ‘artificial kidney’ (haemodialysis) machine as part of the management of kidney failure.
  • Preventing blood from clotting when it is filtered through a machine during heart-lung bypass surgery.

How does heparin injection work?

Heparin sodium injection is a type of medicine called an anticoagulant. It is used to stop blood clots forming within the blood vessels. Heparin sodium is sometimes referred to as standard or unfractionated heparin.

Blood clots normally only form to stop bleeding that has occurred as a result of injury to the tissues. The clotting process is complicated and begins when blood cells called platelets clump together and produce chemicals that activate the clotting process. The final part of this process involves a substance called thrombin being activated to produce a protein called fibrin. Fibrin binds the platelets together, forming a blood clot. This is the body’s natural way of repairing itself.

Heparin works by inactivating thrombin in the clotting process. This stops the formation of fibrin and so stops blood clots forming. Heparin is used to treat blood clots that have formed abnormally inside the blood vessels. It can also be used to prevent these types of dangerous blood clots.

A blood clot that forms abnormally within the blood vessels is known as a thrombus. It can be dangerous because the clot may detach and travel in the bloodstream (where it becomes known as an embolus) and may eventually get lodged in a blood vessel, thereby blocking the blood supply to a vital organ such as the heart, brain or lungs. This is known as a thromboembolism.

Some people have an increased tendency for blood clots to form within the blood vessels. This is usually due to a disturbance in the blood flow within the blood vessels. For example, in coronary artery disease, fatty deposits (atherosclerosis) on the walls of the coronary arteries can disrupt the blood flow, giving a tendency for platelets to clump together and start off the clotting process. Unstable coronary artery disease means that a furred up bit of the artery has ruptured and a clot has formed on it, reducing the flow of blood to the heart. This causes chest pain (angina) and can result in a heart attack.

Slow blood flow in the leg and pelvic veins can also result in clots forming in these blood vessels (deep vein thrombosis). These clots can break off and travel to the lungs (pulmonary embolism). Being immobile for long periods of time, for example due to a severe medical condition or following surgery, can increase the risk of these types of blood clot, as can pregnancy, obesity and certain blood disorders.

How is heparin injection given?

Heparin is given by injection or drip into a vein (intravenously) or by injection under the skin (subcutaneously) to treat and prevent these types of blood clots. The dose and length of treatment used will depend on the nature of the clot being treated or prevented.

Important information about heparin injection

  • While you are receiving treatment for a blood clot with this medicine you will need to have regular blood tests, usually on a daily basis, to check the length of time it takes your blood to clot. This is so that your dose can be adjusted to ensure that the lowest effective dose is used at all times, thus reducing the risk of bleeding.
  • If you receive this medicine for longer than five days you will need to have regular blood tests to check the level of blood cells called platelets in your blood. This is because heparin can sometimes cause the number of platelets in your blood to fall – a condition known as thrombocytopenia. If this happens, the heparin will need to be stopped and alternative treatment used.
  • The amount of potassium in your blood will also be checked in the blood tests, particularly if you have been receiving heparin for longer than seven days. This is because heparin can sometimes cause the amount of potassium in your blood to rise too high. This is called hyperkalaemia. Some people may be at a greater risk of this, for example those with diabetes or kidney problems, or people taking other medicines that can cause potassium to be retained in the body.

Heparin injection should be used with caution in

  • Elderly people
  • Decreased liver function
  • Decreased kidney function
  • Chronic kidney failure
  • Diabetes mellitus
  • High level of potassium in the blood (hyperkalaemia)
  • Increase in the acidity of the blood (metabolic acidosis)
  • Hypersensitivity to low molecular weight heparins, eg dalteparin.

Heparin injection should not be used in

  • People with low numbers of blood cells called platelets in their blood (thrombocytopenia)
  • People who have previously developed a reduced platelet count due to treatment with heparin (heparin-associated thrombocytopenia)
  • People who are actively bleeding
  • People who are more prone to bleeding than normal, eg due to the blood clotting disorder haemophilia
  • Peptic ulcer
  • Very high blood pressure (severe hypertension)
  • Bacterial infection of the heart valves and the lining surrounding the heart (bacterial endocarditis)
  • People who have recently had bleeding in the brain (cerebral haemorrhage), eg a haemorrhagic stroke
  • People who have had recent injury or surgery to the brain, spinal cord, or eyes
  • People who are due to have spinal or epidural anaesthesia or lumbar puncture
  • Severe liver disease.

This medicine should not be used if you are allergic to one or any of its ingredients. Please inform your doctor or pharmacist if you have previously experienced such an allergy.

If you feel you have experienced an allergic reaction, stop using this medicine and inform your doctor or pharmacist immediately.

Pregnancy and breastfeeding

Certain medicines should not be used during pregnancy or breastfeeding. However, other medicines may be safely used in pregnancy or breastfeeding providing the benefits to the mother outweigh the risks to the unborn baby. Always inform your doctor if you are pregnant or planning a pregnancy, before using any medicine.

  • Heparin is often used to prevent blood clots in pregnant women who are at high risk of clots, for example due to a blood clotting disorder or because they have an artificial heart valve. Heparin does not cross the placenta and so does not enter the baby’s bloodstream. It does not cause birth defects. However, some multidose vials of heparin contain benzyl alcohol and this should be avoided during pregnancy. Long-term use of heparin during pregnancy can cause weakening of the mother’s bones (osteoporosis). There may also be an increased risk of bleeding during the pregnancy, or after delivery. You should discuss this with your doctor. As with all medicines, heparin should only be use during pregnancy if the benefits outweigh any possible risks.
  • Heparin does not pass into breast milk. It can be used safely in mothers who are breastfeeding.

Possible side effects of heparin injection

Medicines and their possible side effects can affect individual people in different ways. The following are some of the side effects that are known to be associated with this medicine. Because a side effect is stated here, it does not mean that all people using this medicine will experience that or any side effect.

  • Bleeding
  • High blood potassium level (hyperkalaemia)
  • Decrease in the number of platelets in the blood (thrombocytopenia)
  • Breakdown of skin cells
  • Thinning of the bones (osteoporosis) with long term use
  • Hair loss (alopecia) may be experienced after prolonged use
  • Blood clots in the spinal cord (spinal haematoma) in people having spinal or epidural anaesthesia or lumbar puncture while receiving heparin.

The side effects listed above may not include all of the side effects reported by the medicine’s manufacturer. For more information about any other possible risks associated with this medicine, please read the information provided with the medicine or consult your doctor or pharmacist.

If you think you have experienced a side effect from a medicine or vaccine you should check the patient information leaflet. This lists the known side effects and what to do if you get them. You can also get advice from your doctor, nurse or pharmacist. If they think it’s necessary they’ll report it for you.

You can also report side effects yourself using the yellow card website:

How can heparin injection affect other medicines?

It is important to tell your doctor or pharmacist what medicines you are already taking, including those bought without a prescription and herbal medicines, before you start treatment with this medicine. Similarly, check with your doctor or pharmacist before taking any new medicines while having treatment with this one, to ensure that the combination is safe.

There may be an increased anti-blood-clotting effect, which can result in an increased risk of bleeding or increased time taken to stop bleeding, if any of the following medicines are used in combination with heparin:

  • antiplatelet (‘blood-thinning’) medicines, such as aspirin, dipyridamole, clopidogrel
  • clot-busting medicines (fibrinolytics) such as streptokinase, alteplase
  • dextrans
  • non-steroidal anti-inflammatory drugs (NSAIDs), such as diclofenac, ibuprofen, naproxen
  • oral anticoagulants, such as warfarin, nicoumalone, phenindione.

If you are given any of these your doctor or pharmacist will adjust the doses of your medicines so that the appropriate effect on your blood clotting time is achieved.

There may an increased risk of a rise in the amount of potassium in your blood if heparin is used in combination with the following medicines, which can also raise blood potassium:

  • ACE inhibitors, eg enalapril, captopril
  • angiotensin II receptor antagonists, eg losartan, valsartan
  • potassium-sparing diuretics, eg triamterene, spironolactone, amiloride
  • potassium supplements
  • potassium salts.

The amount of potassium in your blood should be regularly monitored if you are taking any of these while being treated with heparin.

The anticoagulant effect of heparin may be reduced by drips (intravenous infusions) of nitrate medicines such as glyceryl trinitrate.

Further reading

For background information about our medicine factsheets, including the references used to produce them, .

Last updated 06.02.2007

Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are important, lifesaving pharmacotherapeutic agents for those with disorders such as coronary artery disease and other ischemic coronary events, atrial fibrillation, heart valve diseases, stroke, pulmonary embolism, and deep venous thrombosis. But there is a potential for many side effects with the use of these agents. Hence it is important to do a risk-benefit analysis before prescribing them to patients. The possible side effects of therapy should be told to the patients and their families before these agents are administered. Because heparins are usually given in life threatening situations where time is critical, the facts should be presented clearly with the risk-benefit analysis concisely conveyed to the patient and family. When complications do occur, physicians have to be candid with the patient and treat the complications rather than trying to conceal them.

UFH and LMWH therapy are associated with a high rate of drug-related problems and side effects due to either their inherent pharmacological properties or human errors. Thrombocytopenia, bleeding events, and osteopenia are the 3 most common drug-related problems associated with heparin and LMWH therapy. These side effects often complicate treatment and increase the overall cost of care. The Institute for Safe Medication Practices has classified both UFH and LMWH as high-alert drugs. Approximately 2.1 percent of the total records submitted to the MedMARx national error database were related to UFH; 4.5-5.5 percent of the reported errors were harmful .

Heparin-induced Thrombocytopenia (HIT) and Heparin-induced Thrombocytopenia with Thrombosis (HITT)

HIT occurs in 3 to 5 percent of patients who receive intravenous unfractionated heparin compared to the 0.5 percent incidence rate with subcutaneous LMWH, catheter flushes, and even the minuscule amounts of heparin that leach from coated catheters. HIT can precipitate an extreme prothrombotic diathesis known as HITT, resulting in venous or arterial thromboemboli in 50 percent of patients. Without prompt and effective treatment, likely outcomes are limb amputation in 10 to 20 percent of cases, death in 20 to 30 percent of patients, and residual deficits in survivors that can contribute to strokes, myocardial infarctions, and pulmonary emboli. When platelet counts decrease significantly (usually 50 percent of baseline), heparin should be stopped immediately, and, if anticoagulation is necessary, direct thrombin inhibitors like lepirudin or argatroban should be started .

Suppose that a 68-year male is admitted to the intensive care unit with pneumonia and septic shock. He is started on antibiotics, IV fluids, and other supportive measures. He is also given subcutaneous heparin for prophylaxis against deep venous thrombosis. On the eighth day, he develops severe left lower extremity pain. His limbs become blue, and the dorsalis pedis pulse is not palpable. His platelet count drops from 220 000 on admission to 55 000. He is taken to the operating room for an amputation of the leg, below the knee.

This case demonstrates the phenomenon of heparin-induced thrombocytopenia with thrombosis (HITT) and illustrates the need to monitor platelet counts very closely during the course of heparin—even subcutaneous heparin—therapy. HIT can lead to HITT, which can cause severe harm. The early identification of HIT and subsequent termination of heparin therapy can prevent complications.

Hemorrhagic Complications with Heparins

The major complication of anticoagulant therapy is bleeding. LMWH is associated with less major bleeding than UFH. The ease of use, absence of mandatory laboratory monitoring, and clinical efficacy of LMWH have led to its widespread use for anticoagulation therapy in a number of disorders. LMWH is excreted entirely by the kidneys, and, accordingly, in the absence of data regarding safety, it should not be used in patients with compromised renal function. UFH, however, is rapidly metabolized by a saturable, zero-order mechanism, mainly by the reticuloendothelial system. Metabolism is followed by a slower first-order renal clearance. Less than 10 percent is excreted unchanged in urine. The mean half-life is dependent on the administered dose and is unchanged when renal function is normal.

Now, suppose that an 84-year-old female is admitted for shortness of breath. She is frail, weighing only 92 lbs. Routine labs reveal hemoglobin of 12.8 and a creatinine of 1.3, and she is found to have deep venous thrombosis of her right lower extremity. A perfusion scan of her lungs is consistent with a pulmonary embolism. She is started on low molecular weight heparin and other supportive measures. She improves but on the third day of treatment, develops severe hematuria and gastrointestinal bleeding; her hemoglobin falls to 8.6.

This situation demonstrates the drawbacks of using LMWH in patients with renal failure. It also emphasizes the need to calculate creatinine clearance (CrCl), rather than just serum creatinine in elderly and frail patients. The calculated creatinine clearance in this case is 21 ml/min. At such low ranges of creatinine clearance, LMWH can cause hemorrhaging and should not be used.

It is recommended that UFH be used to provide full anticoagulation therapy in patients with severe renal insufficiency. If LMWH is chosen, monitoring should be performed with therapeutic anti-factor Xa activity. The lowest ratio of CrCl levels for patients in this indication category probably varies for different LMWHs, but a safe threshold is likely to be 30 mL/min.

When LMWH is used in patients with mild to moderate renal failure, anti-factor Xa levels should be tested to monitor therapy. This test should also be used when LMWH is administered to obese patients because they are more likely to receive inappropriate doses when weight-adjusted regimens are used.

When using UFH the following should be noted:

  • There is an increased rate of major bleeding with intermittent intravenous (IV) heparin compared with continuous IV infusion; continuous IV heparin and subcutaneous heparin are associated with a similar amount of bleeding.
  • The risk of heparin-associated bleeding increases with concomitant thrombolytic therapy or GP IIb/IIIa antagonists.
  • Renal failure, patients aged over 70 years, and female gender have also been implicated as risk factors for heparin-induced bleeding.
  • There is good evidence that comorbid conditions, particularly recent surgery or trauma, are important risk factors for heparin-induced bleeding .

When bleeding occurs with UFH therapy, protamine should be used to reverse the effects of heparin. However, protamine appears to neutralize only approximately 60 percent of the anti-factor Xa activity of LMWH.

Heparin-associated Osteoporosis

Heparin-associated osteopenia and osteoporosis are rare but potentially serious complications of heparin and LMWH therapy. Both are associated with long-term therapy (usually greater than 1 month) and often occur during pregnancy and the postpartum period when it can result in spontaneous fractures. Factors that contribute to development of these conditions are overactivation of osteoclasts by parathormone, decreased activity of osteoblasts, increased bone resorption as a result of abnormal collagen activation, and disturbances in vitamin D metabolism. Additionally, limited sun exposure during pregnancy and increased calcium demands during lactation can cause an osteoporotic state .

Imagine that a 31-year female with systemic lupus erythematosis and a history of 3 spontaneous abortions is diagnosed with antiphospholipid antibody syndrome. She is put on heparin therapy for the duration of her fourth pregnancy, after which she delivers a full-term healthy baby. During the postpartum period, she sustains a hip fracture after a trivial fall.

The hypothetical situation illustrates a typical scenario where long-term anticoagulation in pregnancy led to a fracture in the postpartum period. This result cannot be totally guarded against, but certain precautions can be taken. Adequate calcium and vitamin D supplementation is one potential prophylatic measure. It is also of note that LMWH presents less risk for osteoporosis than UFH and should be preferred in this setting.

  • Ethics/Practice,
  • Evidence-based practice/Effectiveness
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