• Metabolism: Liver and the reticulo-endothelial system are the sites of biotransformation. The metabolic fate of heparin is not well understood. Route of Elimination: The drug appears to be removed mainly by the reticuloendothelial system. A small fraction of unchanged heparin also appears to be excreted in urine. Heparin cannot be eliminated by hemodialysis. Half Life: 1.5 hours. The plasma half-life of heparin increases from about 60 minutes with a 100 unit/kg dose to about 150 minutes with a 400 unit/kg dose.
• Uses/Sources: Unfractionated heparin is indicated for prophylaxis and treatment of venous thrombosis and its extension, prevention of post-operative deep venous thrombosis and pulmonary embolism and prevention of clotting in arterial and cardiac surgery. In cardiology, it is used to prevent embolisms in patients with atrial fibrillation and as an adjunct antithrombin therapy in patients with unstable angina and/or non-Q wave myocardial infarctions (i.e. non-ST elevated acute coronary artery syndrome) who are on platelet glycoprotein (IIb/IIIa) receptor inhibitors. Additionally, it is used to prevent clotting during dialysis and surgical procedures, maintain the patency of intravenous injection devices and prevent in vitro coagulation of blood transfusions and in blood samples drawn for laboratory values.
• Health Effects: A serious side-effect of heparin is heparin-induced thrombocytopenia (HIT), caused by an immunological reaction that makes platelets a target of immunological response, resulting in the degradation of platelets, which causes thrombocytopenia. This condition is usually reversed on discontinuation, and in general can be avoided with the use of synthetic heparins. Also, a benign form of thrombocytopenia is associated with early heparin use, which resolves without stopping heparin. Two nonhemorrhagic side-effects of heparin treatment are known. The first is elevation of serum aminotransferase levels, which has been reported in as many as 80% of patients receiving heparin. This abnormality is not associated with liver dysfunction, and it disappears after the drug is discontinued. The other complication is hyperkalemia, which occurs in 5 to 10% of patients receiving heparin, and is the result of heparin-induced aldosterone suppression. The hyperkalemia can appear within a few days after the onset of heparin therapy. More rarely, the side-effects alopecia and osteoporosis can occur with chronic use. As with many drugs, overdoses of heparin can be fatal. In September 2006, heparin received worldwide publicity when three prematurely born infants died after they were mistakenly given overdoses of heparin at an Indianapolis hospital. (Wikipedia)
• Symptoms: Heparin sodium - Mouse, median lethal dose greater than 5000 mg/kg. Another side effect is heparin induced thrombocytopenia (HIT syndrome). HIT is caused by an immunological reaction that makes platelets form clots within the blood vessels, thereby using up coagulation factors
• Treatment: Protamine sulfate (1 mg per 100 units of heparin that had been given over the past four hours) has been given to counteract the anticoagulant effect of heparin. (Wikipedia)
• Route of Exposure: Intravenous, Irrigation, Subcutaneous, Intraperitoneal injection Heparin must be given parenterally as it is not absorbed through the gastrointestinal mucosa. It is usually given by iv infusion or deep sc injection. The onset of action is immediate after iv injection but can be delayed 20 to 60 minutes following sc injection. Plasma heparin concentrations may be increased and activated partial thromboplastin times (aPTTs) may be more prolonged in geriatric adults (older than 60 years of age) compared with younger adults.

Heparin-induced thrombocytopenia (HIT) is caused by the formation of abnormal antibodies that activate platelets. Heparin occurs naturally in the human body, but the development of HIT antibodies suggests heparin sulfate may act as a hapten, and thus be targeted by the immune system. In HIT, the immune system forms antibodies against heparin when it is bound to a protein called platelet factor 4 (PF4). These antibodies are usually of the IgG class and their development usually takes about five days. However, those who have been exposed to heparin in the last few months may still have circulating IgG, as IgG-type antibodies generally continue to be produced even when their precipitant has been removed. This is similar to immunity against certain microorganisms, with the difference that the HIT antibody does not persist more than three months. HIT antibodies have been found in individuals with thrombocytopenia and thrombosis who had no prior exposure to heparin sulfate, but the majority are found in people who are receiving heparin. The IgG antibodies form a complex with heparin and PF4 in the bloodstream. The tail of the antibody then binds to the FcγIIa receptor, a protein on the surface of the platelet. This results in platelet activation and the formation of platelet microparticles, which initiate the formation of blood clots; the platelet count falls as a result, leading to thrombocytopenia. (Wikipedia) The cause of the serum aminotransferase elevations during heparin therapy is not known, but it is likely due to a direct hepatotoxic effect on the liver (L2102). Heparin-induced hyperkalemia is the result of heparin-induced aldosterone suppression (Wikipedia). The most important, but probably not the only mechanism of aldosterone inhibition appears to involve reduction in both the number and affinity of the angiotensin-II receptors in the zona glomerulosa (A15335). Alopecia connected to chronic heparin use may be due to the antimitotic effect of heparin on the epithelial cells (A15336). Heparin causes bone loss by decreasing bone formation. The few studies of the mechanism of bone loss have revealed decreased bone formation, increasing bone resorption, or both (L2103).