Heparin and low-molecular-weight heparin: mechanisms of action, pharmacokinetics, dosing, monitoring, efficacy, and safety.

Abbreviations: ACT 5 activated clotting time; APTT 5 activated partial thromboplastin time; AT 5 antithrombin; AT-III 5 antithrombin III; CI 5 confidence interval; DVT 5 deep vein thrombosis; GP 5 glycoprotein; HIT 5 heparininduced thrombocytopenia; INR 5 international normalized ratio; LMWH 5 low-molecular-weight heparin; MI 5 myocardial infarction; NQMI 5 non-Q-wave myocardial infarction; OR 5 odds ratio; PE 5 pulmonary embolism; PF4 5 platelet factor 4; PTCA 5 percutaneous coronary angioplasty; RR 5 relative risk; sc 5 subcutaneous; tPA 5 tissue plasminogen activator; UA 5 unstable angina; UFH 5 unfractionated heparin (CHEST 2001; 119:64S‐94S) H eparin and its derivative, low-molecular-weight heparin (LMWH), are the anticoagulants of choice when a rapid anticoagulant effect is required, because their onset of action is immediate when administered by IV injection. Both types of heparins are administered in lower doses for primary prophylaxis than for treatment of venous thrombosis or acute myocardial ischemia. Heparin has pharmacokinetic limitations 1 not shared by LMWHs. Based on these pharmacokinetic limitations, heparin therapy is usually restricted to the hospital setting, where its effect can be monitored and its dosage adjusted frequently. In contrast, LMWH preparations can be administered in either the in-hospital or out-of-hospital setting because they can be administered subcutaneously (sc) without the need for laboratory monitoring. When longterm anticoagulant therapy is indicated, heparin or LMWH administration is usually followed by treatment with oral anticoagulants. However, long-term out-of-hospital treatment with heparin or LMWH is used when anticoagulant therapy is indicated in pregnancy and in patients who develop recurrent venous thromboembolism while treated with appropriate doses of oral anticoagulants. Since our report in 1998 (Supplement to CHEST, Vol. 114, iss 5), a number of LMWH preparations have been approved for use for the treatment of venous thrombosis and for the treatment of unstable angina (UA). Clinical Indications Heparin is effective and indicated for the prevention of venous thromboembolism; for the treatment of venous thrombosis and pulmonary embolism (PE); for the early treatment of patients with UA and acute myocardial infarction (MI); for patients who undergo cardiac surgery using cardiac bypass, vascular surgery, and coronary angioplasty; in patients with coronary stents; and in selected patients with disseminated intravascular coagulation. LMWHs are effective and indicated for the prevention of venous thromboembolism, for the treatment of venous thrombosis, for the treatment of acute PE, and for the early treatment of patients with UA. The levels of evidence and grading of recommendations for the clinical use of heparin and LMWHs are discussed in the chapters that consider the evidence supporting antithrombotic therapy with these agents for the various clinical indications. This chapter will review the mechanisms of action of heparin and LMWHs, their pharmacokinetics, anticoagulant effects, side effects, and laboratory monitoring. The clinical uses of heparin and LMWHs and the results of clinical trials will also be discussed, although more details appear in other chapters.