Heparin – Uses

Background

Heparin is an anticoagulant indicated for thromboprophylaxis and to treat thrombosis associated with a variety of conditions such as pulmonary embolism and atrial fibrillation. Unfractionated heparin (UH) is a heterogenous preparation of anionic, sulfated glycosaminoglycan polymers with weights ranging from 3000 to 30,000 Da. It is a naturally occurring anticoagulant released from mast cells. It binds reversibly to antithrombin III (ATIII) and greatly accelerates the rate at which ATIII inactivates coagulation enzymes thrombin (factor IIa) and factor Xa. UH is different from low molecular weight heparin (LMWH) in the following ways: the average molecular weight of LMWH is about 4.5 kDa whereas it is 15 kDa for UH; UH requires continuous infusions; activated partial prothrombin time (aPTT) monitoring is required when using UH; and UH has a higher risk of bleeding and higher risk of osteoporosis in long term use. Unfractionated heparin is more specific than LMWH for thrombin. Furthermore, the effects of UH can typically be reversed by using protamine sulfate.

Properties and Characteristics of Diclofenac

Drug class	Glycosaminoglycan, Antithrombotic Agents
Brand Names	Heparin Leo, Hep-Pak (obsolete), Heparin Lock Flush (obsolete), Hep-Pak CVC (obsolete), Hep-Lock (obsolete), Heparin Sodium ADD-Vantage
Synonyms	Eparina, Heparina, Heparine., Heparinic acid, Heparinum, Unfractionated heparin
Molecular Formula	C26H42N2NaO37S5+
Molecular Weight	5,000 to 30,000 daltons
IUPAC Names	sodium;6-[6-[6-[5-acetamido-4,6-dihydroxy-2-(sulfooxymethyl)oxan-3-yl]oxy-2-carboxy-4-hydroxy-5-sulfooxyoxan-3-yl]oxy-2-(hydroxymethyl)-5-(sulfoamino)-4-sulfooxyoxan-3-yl]oxy-3,4-dihydroxy-5-sulfooxyoxane-2-carboxylic acid
Structural formula of main components
Pure active ingredient	Heparin Sodium
Appearance	White or pale-colored amorphous powder
Melting point	>181°C
Solubility	Soluble in water; insoluble in alcohol, benzene, acetone, chloroform, and ether
Excretion	Excreted in urine
Available as	Injectable solution
Storage	Store at room temperature between 68°F and 77°F (20°F and 25°C)
Prescription	Prescription is required

What is heparin used for?

Healthcare providers use heparin to treat or prevent blood clots that can cause you harm. You may receive it if you have:

• Venous thromboembolism (VTE), a blood clot in your vein.
• Deep vein thrombosis (DVT), a clot in a deep vein in your leg or arm.
• Pulmonary embolism (PE), a blood clot that breaks loose from the wall of your vein and travels to your lungs.
• Heart attack.
• Stroke, a blood clot in your brain.
• A blood clot or blockage in one of the arteries in your arms or legs.
• A procedure, surgery or injury that keeps you from being able to move around, such as a joint replacement operation.
• Atrial fibrillation (Afib), a type of abnormal heart rhythm.
• Heart surgery.
• An angioplasty procedure or stent placement in your heart’s arteries.
• Dialysis for failing kidneys.

You may be on heparin temporarily while you’re in the hospital if you have a mechanical heart valve or an acquired or genetic condition that makes you prone to forming blood clots.

Sometimes, pregnant people may need heparin if there’s a concern about losing the fetus. (Heparin doesn’t go through the placenta to a fetus.)

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.

Mechanism of action

Under normal circumstances, antithrombin III (ATIII) inactivates thrombin (factor IIa) and factor Xa. This process occurs at a slow rate. Administered heparin binds reversibly to ATIII and leads to almost instantaneous inactivation of factors IIa and Xa The heparin-ATIII complex can also inactivate factors IX, XI, XII and plasmin. The mechanism of action of heparin is ATIII-dependent. It acts mainly by accelerating the rate of the neutralization of certain activated coagulation factors by antithrombin, but other mechanisms may also be involved. The antithrombotic effect of heparin is well correlated to the inhibition of factor Xa. Heparin is not a thrombolytic or fibrinolytic. It prevents progression of existing clots by inhibiting further clotting. The lysis of existing clots relies on endogenous thrombolytics.

What drugs interact with heparin?

Oral anticoagulants

Heparin sodium may prolong the one-stage prothrombin time. Therefore, when heparin sodium is given with dicumarol or warfarin sodium, a period of at least 5 hours after the last intravenous dose should elapse before blood is drawn if a valid Prothrombin time is to be obtained.

Platelet inhibitors

Drugs such as acetylsalicylic acid, dextran, phenylbutazone, ibuprofen, indomethacin, dipyridamole, hydroxychloroquine and others that interfere with platelet aggregation reactions (the main hemostatic defense of heparinized patients) may induce bleeding and should be used with caution in patients receiving heparin sodium.

Other interactions

Digitalis, tetracyclines, nicotine, antihistamines or I.V. nitroglycerin may partially counteract the anticoagulant action of heparin sodium.

Drug/Laboratory Test Interactions

Hyperaminotransferasemia

Significant elevations of aminotransferase (SGOT [S-AST] and SGPT [SALT]) levels have occurred in a high percentage of patients (and healthy subjects) who have received heparin.

Since aminotransferase determinations are important in the differential diagnosis of myocardial infarction, liver disease, and pulmonary emboli, rises that might be caused by drugs (like heparin) should be interpreted with caution.

Dosage for Heparin

• Heparin is available in vials at strengths of 1000, 5000, 10,000 and 20,000 units per ml.
• Dosage depends on the coagulation problem; many initial doses start with 5000 units IV, but this can change depending on the problem; guidelines for dosages are available.
• If benzyl alcohol is listed as a preservative for the Heparin preparation, do not use in neonates and infants or nursing mothers.
• If preparations without benzyl alcohol are used in pediatric patients, the initial dose is usually 50 units per Kg but a pediatric specialist should be consulted.

What are the causes of Heparin Overdose?

Heparin overdose is most commonly caused by a mistake in the medication dosage, either when a healthcare provider prescribes an incorrect dose or when the patient takes more than the prescribed amount.

Using the medication for longer than recommended or using it in combination with other blood-thinning medications can also cause an overdose.

In some cases, an overdose may occur due to an interaction between Heparin and another medication the patient is taking.

A rare cause of Heparin overdose is HIT (Heparin-induced thrombocytopenia) which is an allergic-like reaction to Heparin that can lead to the formation of blood clots and a decrease in platelets.

In cases where the overdose is caused by HIT, the patient may experience symptoms such as fever, skin rash, and abdominal pain in addition to the symptoms of an overdose.

What Is the Treatment Plan for a Heparin Overdose?

The treatment for a Heparin overdose will depend on the severity of the overdose and the individual’s overall health. For mild overdose, the healthcare provider may simply stop the medication and monitor the patient for any complications.

In more severe cases, the healthcare provider may administer a medication called Protamine sulfate to counteract the effects of Heparin. Protamine sulfate, also known by its generic name, is a medication that belongs to the class of anti-heparin agents. It works by neutralizing the effects of Heparin in cases of overdose. The mechanism of action of Protamine sulfate is that it forms a stable salt with heparin, which neutralizes the anticoagulant activity of both drugs. It is mainly used to treat Heparin overdose, but it is less effective against low molecular weight heparin. The onset of action of Protamine sulfate is rapid and it neutralizes heparin within five minutes. However, it may cause a sudden drop in blood pressure and bradycardia when administered through an intravenous route. Other side effects include flushing, warmth sensation, breathing difficulties, nausea, vomiting, and feeling of tiredness. Anaphylaxis is also a reported side effect of the drug. It should be avoided with certain antibiotics, such as Cephalosporins and Penicillin.

What special precautions should I follow?

Before using heparin,

• Tell your doctor and pharmacist if you are allergic to heparin, any other medications, beef products,pork products, or any of the ingredients in heparin injection. Ask your doctor or pharmacist for a list of the ingredients.
• Tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: other anticoagulants such as warfarin (Coumadin); antihistamines (in many cough and cold products); antithrombin III (Thrombate III); aspirin or aspirin-containing products and other nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Advil, Motrin) and naproxen (Aleve, Naprosyn); dextran; digoxin (Digitek, Lanoxin); dipyridamole (Persantine, in Aggrenox); hydroxychloroquine (Plaquenil); indomethacin (Indocin); phenylbutazone (Azolid) (not available in the US); quinine; and tetracycline antibiotics such as demeclocycline (Declomycin), doxycycline (Monodox, Vibramycin), minocycline (Dynacin, Minocin) and tetracycline (Bristacycline, Sumycin). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• Tell your doctor if you have a low level of platelets (type of blood cells needed for normal clotting) in your blood and if you have heavy bleeding that cannot be stopped anywhere in your body. Your doctor may tell you not to use heparin.
• Tell your doctor if you are currently experiencing your menstrual period; if you have a fever or an infection; and if you have recently had a spinal tap (removal of a small amount of the fluid that bathes the spinal cord to test for infection or other problems), spinal anesthesia (administration of pain medication in the area around the spine), surgery, especially involving the brain, spinal cord or eye, or a heart attack. Also tell your doctor if you have or have ever had a bleeding disorder such as hemophilia (condition in which the blood does not clot normally), antithrombin III deficiency (condition that causes blood clots to form), blood clots in the legs, lungs, or anywhere in the body, unusual bruising or purple spots under the skin, cancer, ulcers in the stomach or intestine, a tube that drains the stomach or intestine, high blood pressure, or liver disease.
• Tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while using it, call your doctor.
• If you are having surgery, including dental surgery, tell the doctor or dentist that you are using heparin.
• Tell your doctor if you smoke or use tobacco products and if you stop smoking at any time during your treatment with heparin. Smoking may decrease the effectiveness of this medication.