Low-molecular-weight heparin
Low-molecular-weight heparin (LMWH) is a class of anticoagulant medications.[1] They are used in the prevention of blood clots and, in the treatment of venous thromboembolism (deep vein thrombosis and pulmonary embolism), and the treatment of myocardial infarction.
Pharmacokinetic data
100%
4-6 kDa
Heparin is a naturally occurring polysaccharide that inhibits coagulation, leading to thrombosis. Natural heparin consists of molecular chains of varying lengths or molecular weights. Chains of varying molecular weights, from 5000 to over 40,000 daltons, make up polydisperse pharmaceutical-grade heparin.[2] LMWHs, in contrast, consist of only short chains of polysaccharides. LMWHs are defined as heparin salts having an average molecular weight of less than 8000 Da and for which at least 60% of all chains have a molecular weight less than 8000 Da. Various methods of fractionation or depolymerization of polymeric heparin obtain these.
Heparin derived from natural sources, mainly porcine intestine or bovine lung, can be administered therapeutically to prevent thrombosis. However, the effects of natural or unfractionated heparin are more unpredictable than LMWH.[3]
Medical uses[edit]
Because it can be given subcutaneously and does not require APTT monitoring, LMWH permits outpatient treatment of conditions such as deep vein thrombosis or pulmonary embolism that previously mandated inpatient hospitalization for unfractionated heparin administration.
Because LMWH has more predictable pharmacokinetics and anticoagulant effects, LMWH is recommended over unfractionated heparin for patients with massive pulmonary embolism[4] and for initial treatment of deep vein thrombosis.[5] As compared to placebo or no intervention, prophylactic treatment of hospitalized medical patients using LMWH and similar anticoagulants reduces the risk of venous thromboembolism, notably pulmonary embolism.[6][7]
More recently, these agents have been evaluated as anticoagulants in acute coronary syndrome (ACS) and managed by percutaneous intervention (PCI).[8][9]
The use of LMWH needs to be monitored closely in patients at extremes of weight or in patients with renal dysfunction. An anti-factor Xa activity may be useful for monitoring anticoagulation. Given its renal clearance, LMWH may not be feasible in patients with end-stage renal disease. LMWH can also be used to maintain the patency of cannulae and shunts in dialysis patients.
Patients with cancer are at higher risk of venous thromboembolism, and LMWHs are used to reduce this risk.[10] The CLOT study, published in 2003, showed that dalteparin was more effective in patients with malignancy and acute venous thromboembolism than warfarin in reducing the risk of recurrent embolic events.[11] The use of LMWH in cancer patients for at least the first 3 to 6 months of long-term treatment is recommended in numerous guidelines and is now regarded as a standard of care.[10]