low-molecular-weight heparin low-molecular-weight heparin low-molecular-weight heparin (lmwh) is a class of anticoagulant medications. they are used in the prevention of blood clots and treatment of venous thromboembolism (deep vein thrombosis and pulmonary embolism) and in the treatment of myocardial infarction. low-molecular-weight heparinnadroparin in prefilled syringepharmacokinetic databioavailability100%chemical and physical datamolar mass4-6 kda heparin is a naturally occurring polysaccharide that inhibits coagulation, the process that leads 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. lmwhs, in contrast, consist of only short chains of polysaccharide. 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. these are obtained by various methods of fractionation or depolymerisation of polymeric heparin. 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. medical uses 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 effect, lmwh is recommended over unfractionated heparin for patients with massive pulmonary embolism, and for initial treatment of deep vein thrombosis. 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. more recently these agents have been evaluated as anticoagulants in acute coronary syndrome (acs) managed by percutaneous intervention (pci). 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 that have 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. the clot study, published in 2003, showed that, in patients with malignancy and acute venous thromboembolism, dalteparin was more effective than warfarin in reducing the risk of recurrent embolic events. 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. contraindications the use of lmwhs should be avoided in patients with known allergies to lmwhs, heparin, sulfites or benzyl alcohol, in patients with active major bleeding, or patients with a history of heparin-induced low blood platelet count (also known as heparin-induced thrombocytopenia or hit). high treatment doses are contraindicated in acute bleedings such as cerebral or gastrointestinal haemorrhage. lmwhs are more dependent on renal function for their excretion than unfractionated heparin so their biological half-life may be prolonged in patients with kidney failure and therefore their use in the setting of creatinine clearance rate (crcl) <30 ml/min may need to be avoided. apart from using unfractionated heparin instead, it may be possible to reduce the dose and/or monitor the anti-xa activity to guide treatment. the most common side-effects include bleeding, which could be severe or even fatal, allergic reactions, injection site reactions, and increases in liver enzyme tests, usually without symptoms. the use of heparin and lmwhs can sometimes be complicated by a decrease in platelet count, a complication known as heparin induced thrombocytopenia.13 two forms have been described: a clinically benign, non-immune and reversible form (type i) and a rare, more serious immune-mediated form or type ii. hit type ii is caused by the formation of auto antibodies that recognize complexes between heparin and platelet factor 4 (pf4) and is therefore associated with a substantial risk of thrombotic complications. the incidence is difficult to estimate but may reach up to 5% of patients treated with ufh or about 1% with lmwh. antidote in clinical situations in which the antithrombotic effect of lmwhs needs to be neutralized, protamine is used to neutralize heparin by binding to it. studies in animals and in vitro studies have demonstrated that protamine neutralizes the antithrombin activity of lmwhs, normalizing the aptt and thrombin time. however, protamine appears to only partially neutralize the anti-factor xa activity of lmwh. because the molecular weight of heparin impacts its interaction with protamine, it is likely that the lack of complete neutralization of anti-factor xa is due to a reduced protamine binding to the lmwhs moieties in the preparation. protamine is a medicine that requires a high level of caution when used. precautions lmwh trials usually excluded individuals with unpredictable pharmacokinetics, and as a result patients with risks such as the severely obese or in advanced stages of kidney failure show decreased benefits due to fractionated heparin's increased half-life. lmwhs should be used with extreme caution in patients undergoing any procedure involving spinal anaesthesia/puncture, in conditions with increased risk of bleeding or in patients with a history of heparin-induced thrombocytopenia. pharmacology mechanism of action