Description

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: 
a. 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. 

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NDA 17-037/S-158 
Page 8 
b. 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. 
c. Retroperitoneal 
hemorrhage. 
Thrombocytopenia, Heparin-induced thrombocytopenia (HIT) and Heparin-induced 
Thrombocytopenia and Thrombosis (HITT) and Delayed Onset of HIT and HITT:
see WARNINGS. 
 
Local Irritation 
Local irritation, erythema, mild pain, hematoma or ulceration may follow deep subcutaneous (intrafat) 
injection of heparin sodium. These complications are much more common after intramuscular use, and 
such use is not recommended. 
Hypersensitivity 
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 side 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. 
Miscellaneous 
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 [S-AST] and SGPT [S-ALT]) levels have occurred 
in a high percentage of patients (and healthy subjects) who have received heparin.