Heparin: Indications and Side Effects

Heparin is a very effective drug, but it must be administered under strict medical supervision. It has an anticoagulant function and is capable of saving lives in emergency situations.
Heparin: Indications and Side Effects
Diego Pereira

Written and verified by el médico Diego Pereira.

Last update: 17 April, 2023

Heparin is an anticoagulant that has been used for decades, and is still one of the most used and recommended by doctors in emergency situations. There are two classifications, depending on the molecular size, and each one has a different prescription.

It’s considered a safe drug, despite the fact that there are several adverse reactions that can appear in patients with some pre-existing conditions. It’s administered subcutaneously or intravenously and is well tolerated during pregnancy.

What is heparin?

It’s one of the main anticoagulant drugs for parenteral administration on the market today. In fact, it’s included in the list of essential medicines of the World Health Organization (WHO), due to its wide variety of indications and ease of administration.

In the human body, heparin can be found in mast cells, lung, and liver cells. This latter organ is also indirectly involved with other processes to maintain hemostasis. Some coagulation factors, which are proteins that are an active part of this process, are synthesized in the liver.

It’s one of the oldest drugs still in clinical use. Discovered in 1918 by a medical student at Johns Hopkins School, at that time under instructions from his tutor, with whom he was analyzing the properties of certain compounds derived from dogs’ livers.

Over the years, the great potential this drug could have to treat some of the most dangerous diseases became evident.

Mechanism of action

Hemostasis is a term that encompasses the set of processes that occur within blood vessels to stop bleeding. It’s influenced by factors that promote blood coagulation and others that inhibit it.

In certain pathological conditions, procoagulant factors may predominate and cause conditions such as deep vein thrombosis or pulmonary thromboembolism. As we’ll discuss later, these are conditions with high morbidity and mortality due to the obstruction of blood flow.

For this, anticoagulants are used, since they can partially or totally reverse this process. In the case of heparin, it first acts on a substance called antithrombin III (ATIII). When this happens, molecules called coagulation factors are blocked or inhibited.

After these reactions, the creation of new clots decreases and the progression of a disease that could be fatal is slowed down. The range of activity on the different coagulation factors depends a lot on the type of heparin that we’re considering.

Blood clot blocked by heparin.
Heparin stops clots from forming to prevent life-threatening processes.

Types of heparin

There are two large groups of heparin: unfractionated (UFH) and low molecular weight (LMWH). Both are administered parenterally, but they have clear differences that make them more suitable for certain types of conditions.

In general terms, LMWHs are obtained from UFH processing. This is accomplished by adding chemicals or enzymes that depolymerize the large UFH molecule. The latter, by the way, has a very high charge density.

Unfractionated heparin (UFH)

A few decades ago it was the most widely used, but over time it was displaced by new drugs. It has a much broader range of activity than LMWH, as it’s capable of inhibiting more procoagulant molecules. Some of these are factors XIa, IXa, and VIIa.

It has the advantage of being able to be administered both subcutaneously and intravenously. The first of these is achieved by means of an injection, generally at the abdominal level, in which the syringe or injector must be inclined about 45 degrees.

If it’s administered in this way, the amount of the drug that reaches the blood circulation is between 30 to 90%, which is much less than the most modern HPBM. This means that higher doses are needed to achieve the desired concentration in the blood.

It has an elimination half-life of between 30 minutes and 1.5 hours. This can be positive or negative. As it has a short activity time, more doses may be required to maintain a constant effect.

In addition, it’s eliminated through the kidneys and the liver. Patients receiving this treatment require continuous monitoring which is accomplished by performing a test called aPTT or activated partial thromboplastin time.

Low Molecular Weight Heparin (LMWH)

There are several drugs within this group, including enoxaparin, dalteparin, bemiparin, nadroparin and tinzaparin. Although they have similar activity, they aren’t the same, and so the dosage and indications depend on the specific drug.

Its use has important benefits compared to UFH. Although it has specific activity with only one procoagulant element (factor Xa), its bioavailability is greater than 90%, so most of the administered dose reaches the circulation.

It has a half-life of about 4 hours, added to the fact that it doesn’t require continuous monitoring of aPTT levels. This is considered a great advantage, as it reduces the need for medical consultations and the risk of adverse effects.

Heparin indications

Either form of heparin is used for the prevention and treatment of venous thromboembolic diseases. This includes pulmonary embolism (PE) and deep vein thrombosis (DVT).

In PE, one or more clots obstruct blood flow to the lungs, making perfusion and subsequent ventilation difficult. As a consequence, the oxygen saturation in the blood decreases and the organs begin to fail. From a clinical point of view, it’s characterized by a sudden increase in respiratory and heart rate, difficulty breathing, and hemoptysis (coughing up blood).

In turn, there are many risk factors that can cause these conditions. Orthopedic or thoracic surgeries, a sedentary lifestyle, prolonged immobilization in patients with disabilities, chemotherapy for cancer, nephrotic syndrome, obesity, smoking, pregnancy, and congenital thrombophilia are some of them.


As it’s a drug that inhibits certain coagulation factors, it should be avoided in situations where there’s a tendency to bleed. This is more important in those that immediately compromise life. The following would be contraindications:

  • Gastric ulcer and inflammatory bowel disease with associated digestive bleeding.
  • Active heavy menstruation.
  • Dissecting aortic aneurysm.
  • Hemophilia.
  • Severe thrombocytopenia: decreased platelet count.
  • Congenital coagulopathies.

Although heparin is found in the human body, the heparin marketed as a medicine comes from porcine or bovine tissues. Therefore, patients who have a known allergy to proteins from these animals could develop reactions.

Adverse effects of heparin

The main side effects derived from its use include bleeding and heparin-induced thrombocytopenia. The first, as we mentioned in the previous section, is more common in patients with certain pre-existing medical conditions.

The second pathology can occur through various mechanisms and has variable severity. There may be mild cases in which the platelet count decreases, which tend to be reversible spontaneously and don’t involve autoimmune mechanisms.

However, according to publications in the Spanish Journal of Cardiology, there are also severe forms of thrombocytopenia that include the participation of IgG type autoantibodies. This means that platelets tend to be destroyed in the blood, so their concentration decreases. This syndrome occurs much more in intravenous UFH treatments after a heart transplant or orthopedic surgery.

Blood with its cells.
Platelets travel through the blood along with red and white blood cells. When they must act, they can agglutinate and aggregate in the area of hemorrhages.


Some medications, by interacting with heparin, increase the risk of complications. They’re the following:

  • Acetylsalicylic acid (aspirin)
  • Warfarin
  • Non-steroidal anti-inflammatory drugs (NSAIDs)
  • Cefoperazone and cefotetan
  • Valproic acid
  • Chloroquine and hydroxychloroquine
  • Nitroglycerine

However, many medical conditions require the co-administration of these drugs. For example, in an acute myocardial infarction, aspirin and heparin may be required as part of the treatment. In these cases, the doctor will assess the risk and benefits.

Can it be administered during pregnancy and lactation?

Pregnancy is, by itself, a situation that promotes clotting. However, it’s very rare for these patients to require treatment such as heparin. If they have mechanical heart valves or have a history of coagulation disorders, the doctor will assess the indication of anticoagulants.

Both UFH and LMWH are well tolerated. It’s possible that some time before the scheduled delivery the doctor will stop the heparin treatment if any anesthesia is going to be administered.

Heparin should be used with care

Heparin is a widely used drug and, despite having few adverse effects, it must be administered with care. Many diseases can make certain patients more susceptible to developing complications, so medical control is always mandatory.

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