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Ardeparin Side Effects

Medically reviewed by Last updated on Jan 10, 2024.

Applies to ardeparin: subcutaneous solution.


Ardeparin was withdrawn from the U.S. market in March of 2000.

There is a risk of bleeding in the spinal or epidural space, possibly resulting in paralysis, when ardeparin is used along with spinal or epidural anesthesia or spinal puncture. This risk may be increased by the use of indwelling epidural catheters or by the concomitant use of drugs that affect blood clotting.

Do not inject this medication intramuscularly (into the muscle) or intravenously (into the vein).

Do not take aspirin, ibuprofen (Motrin, Advil, Nuprin, and others), ketoprofen (Orudis KT, Orudis, Oruvail), naproxen (Aleve, Naprosyn, Anaprox, and others), indomethacin (Indocin), or any other nonsteroidal anti-inflammatory medication without first talking to your doctor. These medicines may lead to bleeding when taken with ardeparin. Ask your pharmacist or doctor before taking any prescription or over-the-counter medication.

If you experience any of the following serious side effects, stop using ardeparin, and seek emergency medical attention or call your doctor immediately:

Other less serious side effects may be more likely to occur. Continue to use ardeparin and notify your doctor if you experience

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome.

For Healthcare Professionals

Applies to ardeparin: subcutaneous solution.


Dose-related hematoma and injection site hemorrhage are the most commonly reported bleeding complications and may occur at any site in the body. However, the incidence of bleeding has been low (5% to 7% of patients). Ecchymosis has also been reported.[Ref]

Any unexplained decrease in blood pressure and/or hematocrit should prompt consideration of a possible hemorrhagic event.[Ref]


Patients undergoing spinal/epidural anesthesia or puncture and anticoagulated or scheduled to be anticoagulated with low molecular weight heparins or heparinoids are at risk for long-term or permanent paralysis due to epidural or spinal hematoma. The risk of these events is increased by the use of indwelling epidural catheters or by concomitant use of platelet inhibitors, other anticoagulants, or drugs that affect hemostasis.

Platelet counts of less than 100,000/mm3 have occurred in 2% of ardeparin-treated patients. Anemia has been reported in greater than 5% of patients. Rarely, post-operative thrombocytosis as well as immune-type thrombocytopenia has been reported. Platelet counts should be monitored in patients receiving ardeparin.[Ref]

A meta-analysis of published studies reported an overall incidence of major bleeding with low molecular weight heparins of 0.7% to 1.4%. Hematologic abnormalities also include thrombocytopenia, thrombocytosis, thrombosis, and hypochromic anemia.

Bleeding due to ardeparin can usually be controlled by discontinuing the ardeparin, applying pressure, and replacing blood volume as needed. If these measures are ineffective, or a known overdose has occurred in a bleeding patient, the manufacturer recommends that protamine sulfate may be used to neutralize the hemorrhagic effects of ardeparin. Protamine should be given at a dose of 1 mg protamine per 100 anti-Xa units of ardeparin.

Additional hemorrhagic events occurring in less than 2% of the studied population include epistaxis, gastrointestinal hemorrhage, hematemesis, hematuria, melena, petechiae, rectal hemorrhage, retroperitoneal hemorrhage, and guaiac-positive stools.

Patients previously exposed to unfractionated heparin or a low-molecular-weight heparin appear to be more susceptible to developing heparin-induced thrombocytopenia (HIT) and HIT-related thromboembolic complications (e.g., transient ischemic attack, stroke) than those who were never exposed.

Heparin-induced thrombocytopenia (HIT) is an immune-mediated, prothrombotic reaction that occurs in 0.5% to 5% of patients treated with unfractionated heparin and in less than 1% of patients treated with a low molecular weight heparin (LMWH). The decrease in platelet count associated with HIT usually begins 5 to 14 days after starting heparin. However, patients with a previous exposure to heparin may have an abrupt decrease in platelets upon restarting heparin. Patients with LMWH-induced HIT exhibit a longer delay in the onset of symptoms compared with those who develop it from unfractionated heparin. Following discontinuation, platelet counts begin to recover within 4 days, but may take more than 2 weeks in patients with high-titer HIT antibodies. Thrombocytopenia is caused by heparin-dependent IgG antibodies that bind to a specific platelet protein, platelet factor 4 (PF4). The heparin-PF4-IgG immune complex binds to platelets causing platelet activation. The activated platelets cause release of platelet-derived procoagulant microparticles, which accelerate coagulation reactions and generates thrombin. LMWHs have a high cross-reactivity with circulating heparin-PF4-IgG immune complex. Factors associated with a higher risk for developing HIT-associated thrombosis include women, nonwhites, severity of thrombocytopenia, and lower body weight. Complications associated with HIT include exacerbation of venous thromboembolism, arterial or venous thrombosis, limb gangrene, stroke, and skin necrosis. The antibodies that cause HIT will usually disappear after approximately 3 months; therefore, use of unfractionated heparin or LMWH may be considered in a patient with a history of HIT if the antibody test is negative.[Ref]


Gastrointestinal adverse effects occurred in greater than 5% of patients during initial clinical trials and included nausea, vomiting and constipation.[Ref]


Local adverse effects of subcutaneous injections include pain, erythema, and hematoma formation. Rarely, patients may experience painful, red indurations and necrosis at the injection site. Hematoma at the injection site occurs with a frequency of approximately 7%. Pruritis and rash may occur rarely.[Ref]


Hepatic adverse effects of ardeparin and other low molecular weight heparins include asymptomatic transient elevations in liver function tests (greater than 3 times the upper limit of normal) which rarely are associated with increases in bilirubin. The elevations in liver function test values are usually reversible and not clinically significant.[Ref]


Hypersensitivity reactions may include urticaria and maculopapular or vesiculobullous rash.[Ref]


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Further information

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Some side effects may not be reported. You may report them to the FDA.