Heparin precautions

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Precautions

General

White − Clot Syndrome

It has been reported that patients on Heparin may develop new thrombus formation in association with thrombocytopenia, resulting from irreversible aggregation of platelets induced by Heparin, the so-called “white − clot syndrome”. The process may lead to severe thromboembolic complications like skin necrosis, gangrene of the extremities that may lead to amputation, myocardial infarction, pulmonary embolism, stroke, and possibly death. Therefore, Heparin administration should be promptly discontinued if a patient develops new thrombosis in association with thrombocytopenia with a reduction in platelet count.

Heparin Resistance

Increased resistance to Heparin is frequently encountered in fever, thrombosis, thrombophlebitis, infections with thrombosing tendencies, myocardial infarction, cancer, and in postsurgical patients, and patients with antithrombin III deficiency.

Increased Risk in Older Women

A higher incidence of bleeding has been reported in women over 60 years of age.

Laboratory Tests

Periodic platelet counts, hematocrits, and tests for occult blood in stool are recommended during the entire course of Heparin therapy, regardless of the route of administration).

Drug Interactions

Drugs Enhancing Heparin Effect

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 or 24 hours after the last subcutaneous 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.

The anticoagulant effect of Heparin is enhanced by concurrent treatment with antithrombin III (human) in patients with hereditary antithrombin III deficiency. Thus in order to avoid bleeding, reduced dosage of Heparin is recommended during treatment with antithrombin III (human).

Drugs Decreasing Heparin Effect

Digitalis, tetracyclines, nicotine, or antihistamines may partially counteract the anticoagulant action of Heparin sodium.

Heparin Sodium Injection should not be mixed with doxorubicin, droperidol, ciprofloxacin, or mitoxantrone, since it has been reported that these drugs are incompatible with Heparin and a precipitate may form.

Intravenous nitroglycerin administered to Heparinized patients may result in a decrease of the partial thromboplastin time with subsequent rebound effect upon discontinuation of nitroglycerin. Careful monitoring of partial thromboplastin time and adjustment of Heparin dosage are recommended during coadministration of Heparin and intravenous nitroglycerin.

When clinical circumstances require reversal of Heparinization, consult the labeling of Protamine Sulfate Injection, USP.

Drug/Laboratory Test Interactions

Hyperaminotransferasemia:

Significant elevations of aminotransferase SGOT (AST) and SGPT (ALT) 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.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No long-term studies in animals have been performed to evaluate the carcinogenic potential of Heparin. Also, no reproduction studies in animals have been performed concerning mutagenesis or impairment of fertility.

Pregnancy

Teratogenic Effects: Pregnancy Category C:

Animal reproduction studies have not been conducted with Heparin sodium. It is also not known whether Heparin sodium can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Heparin sodium should be given to a pregnant woman only if clearly needed.

Nonteratogenic Effects:

Heparin does not cross the placental barrier.

Nursing Mothers

Heparin is not excreted in human milk.

Pediatric Use

Follow recommendations of appropriate pediatric reference texts. In general, the following dosage schedule may be used as a guideline:

• Initial Dose: 50 units/kg (IV drip)
• Maintenance Dose: 100 units/kg (IV drip) every four hours, or 20,000 units/m²/24 hours continuously.

Adapted from the FDA Package Insert.