Bleeding with fondaparinux

FONDAPARINUX ANTICOAGULANTS-PARENTERAL t risk of bleeding when heparins are given with fondaparinux Combined anticoagulant effect Manufacturers recommend avoiding co-administration... 

In a meta-analysis of these studies, bleeding was slightly, but not significantly, more frequent with fondaparinux than with enoxaparin (21,22). 

The primary adverse effect associated with fondaparinux therapy is bleeding." " The rate of major bleeding in the VTE prophylaxis trials was approximately 2% to 3%. The risk of major bleeding appears to be related to weight therefore, in patients who weigh less than 50 kg, fondaparinux is contraindicated for VTE prophylaxis, and the treatment dose is only 5 mg every 24 hours. Similar to UFH and the LMWHs, fondaparinux should be used with extreme caution in patients with neuraxial anesthesia or following a spinal puncture owing to the risk for spinal or epidural hematoma formation. Unlike UFH and the LMWHs, fondaparinux does not cause heparin-induced thrombocytopenia and does not produce cross-sensitivity in vitro." A specific antidote to reverse the antithrombotic activity of fondaparinux is not currently available, but several potential products have been evaluated. 

A single 975-mg dose of aspirin given on day 4 of an 8-day course of subcutaneous fondaparinux 10 mg daily had no effect on fondaparinux pharmacokinetics in 16 healthy subjects. The increase in bleeding time with fondaparinux and aspirin was greater than with aspirin alone, but this was not statistically significant. Aspirin had no effect on the small prolongation of aPTT seen with fondaparinux. ... 

Severe renal impairment (Ccr less than 30 mL/min) fondaparinux as prophylactic therapy in patients with body weight less than 50 kg undergoing hip fracture, hip replacement, or knee replacement surgery active major bleeding bacterial endocarditis thrombocytopenia associated with a positive in vitro test for antiplatelet antibody in the presence of fondaparinux known hypersensitivity to fondaparinux. 

Elderly The risk of fondaparinux-associated major bleeding increased with age. Careful attention to dosing directions and concomitant medications (especially antiplatelet medication) is advised. 

Special populations Use fondaparinux with care in patients with a bleeding diathesis, uncontrolled arterial hypertension, or a history of recent Gl ulceration, diabetic retinopathy, and hemorrhage. 

Contraindications Active major bleeding, bacterial endocarditis, body weight less than 50 kg, severe renal impairment (with creatinine clearance less than 30 ml/min), thrombocytopenia associated with antiplatelet antibody formation in the presence of fondaparinux... 

Adverse effects. When bleeding is induced by heparin, the heparin action can be instantly reversed by protamine. Against fractionated heparins and fondaparinux, protamine is less or not effective. Heparin-induced thrombocytopenia type II (HIT II) is a dangerous complication. It results from formation of antibodies that precipitate with bound heparin on platelets. The platelets aggregate and give rise to vascular occlusions. Because of the thrombocytopenia, hemorrhages may occur. Fondaparinux is also contraindicated in HIT II. 

In the absence of contraindications, the treatment of VTE initially should include a rapid-acting anticoagulant (e.g., unfractionated heparin [UFH], a low-molecular-weight heparin [LMWH], or fondaparinux) overlapped with warfarin for at least 5 days and until the patient s international normalized ratio (INR) is greater than 2.0. Anticoagulation therapy should be continued for a minimum of 3 months. The duration of anticoagulation therapy should be based on the patient s risk of VTE recurrence and major bleeding. 

Fondaparinux has been used safely in elderly patients, but the risk of major bleeding increases with age (1.8% in patients younger than 65 years of age, 2.2% in patients 65 to 74 years of age, and 2.7% in patients 75 years of age or older).This is an important consideration because many patients who undergo orthopedic surgery are elderly. Elderly patients are also more likely to have decreased renal function, and careful assessment of renal status should be conducted prior to initiating therapy. Fondaparinux is contraindicated in patients with a creatinine clearance of less than 30 mL/min. 

Some clinicians advocate strict criteria for the outpatient management of VTE in order to minimize the potential for treatment failure and bleeding complications. These criteria often exclude patients with cancer and the morbidly obese. Proponents of a less restrictive approach argue that strict exclusion criteria unnecessarily withhold outpatient treatment with LMWHs or fondaparinux from those patients who may benefit the most namely, those with cancer. Each health care system must develop outpatient DVT criteria that fit its resources, philosophy, and patient population best. 

The most common side effect is major and minor bleeding, and the patient must be carefully monitored. The drug is not to be used when spinal anesthesia or spinal puncture is employed beoause of the potential for developing a blood clot in the spine. Fondaparinux has not been reported to cause thrombocytopenia, a oondition seen with heparin (56,59,60). It is 100% bioavailable, with little or no protein binding. 

Fondaparinux commonly causes bleeding as a consequence of its action. Since antiplatelet drugs and NSAIDs also increase the risk of bleeding, the risk and severity of bleeding is likely to be increased with the combination. 

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