Unfractionated heparin (UFH) is a mixture of sulfated glycosaminoglycans with molecular weight of 5000 to 30 000 (mean 12 000 to 15 000 depending on the source). Only about one-third of this heparin mixture has significant anticoagulant effect. This occurs by binding to and greatly increasing the activity of antithrombin, an alpha2-globulin that inactivates thrombin, factor Xa and some other activated clotting factors. This causes a dose-dependent effect that must be monitored by activated partial thromboplastin time (APTT). UFH has other effects, including some inhibition of platelet function, increased permeability of vessels, and inhibition of vascular smooth muscle proliferation.

UFH must be administered intravenously or subcutaneously. The biological half-life of intravenous UFH is of the order of 30 to 60 minutes, increasing somewhat with dosage. It binds initially to saturable sites on endothelial cells and is eliminated by mechanisms that are still unclear. Patients with renal failure may have reduced heparin requirements.

Fibrin-bound thrombin is much less readily inactivated than is prothrombin, so higher concentrations are needed to treat than to prevent venous thrombosis and it is relatively ineffective in inhibiting thrombin after coronary thrombolysis.

Even with careful monitoring, major bleeding occurs in up to 6% of patients—and more frequently in patients also taking aspirin, and those with hepatic dysfunction and possibly with renal failure. Protamine (1 mg for every 100 units of UFH) can be used to counteract the anticoagulant effect of heparin in cases of severe haemorrhage. A mild to moderate decrease in platelet count follows the start of heparin treatment in up to 30% of patients. In well under 1% of patients, a more marked, immune-mediated fall in platelets occurs and may be associated with arterial or venous thrombosis (ie heparin-induced thrombocytopenia [HIT]). In patients with heparin-induced thrombocytopenia who require continuing anticoagulant therapy, a heparinoid (danaparoid), which differs chemically from heparin, or a selective inhibitor of thrombin (lepirudin) should be considered, not a low molecular weight heparin (LMWH). If HIT is confirmed, future use of heparin or LMWH is contraindicated. Less common adverse effects of heparin in long-term use include various allergic reactions, alopecia, osteoporosis and mineralocorticoid deficiency.