In the late 1980s, the development of low molecular weight heparins (LMWHs) led to improvements in antithrombotic therapy with clinical advantages including dose predictability, less bleeding and no thrombocytopenia. LMWHs are derived from UFH (Unfractionated heparin) by such processes as chemical degradation, enzymatic depolymerisation and gamma-radiation cleavage. 
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. However, the effects of natural, or unfractionated heparin are more unpredictable than LMWH.
LMWH vs. Unfractioned heparin:
Of particular interest is the fact that their relative effects on platelets are minimal compared to heparin, providing an immediate advantage when treating platelet- compromised patients.  
Fig. 1:  Advantages of low-molecular-weight heparin over unfractionated heparin lmwh tabel
Source: PubMed, Nomura research  
The degree of depolymerisation of UFH can be controlled to obtain LMWH of different lengths. Dosage requirements for the treatment of deep vein thrombosis (DVT) are significantly reduced when employing LMWH as opposed to UFH, although in general the efficacy of both therapeutics seems to be comparable. In addition, LMWH can be effective as an alternative therapeutic for patients who have developed a sensitivity to UFH. 
 There has also recently been a great deal of concern in the use of LMWH due to the perceived potential for cross-species viral contamination as a result of the animal source of the parent UFH. One way of avoiding the possibility of cross-species contamination, is to prepare heparins by chemical synthesis. This method provides the opportunity to develop second generation heparins or heparinoids that can be tailored to target particular biological events in the blood coagulation cascade. 
LMWH mechanism:
Coagulation cascade is a normal physiological process which aims at preventing significant blood loss or hemorrhage following vascular injury. Unfortunately, there are times when a blood clot (thrombus) will form when it is not needed. For instance, some high risk conditions such as prolonged immobilization, surgery, or cancer can increase the risk of developing a blood clot which can potentially lead to significant consequences.
The coagulation cascade consists of a series of steps in which a protease cleaves and subsequently activates the next protease in the sequence. Since each protease can activate several molecules of the next protease in the series, this biological cascade is amplified. The final result of these reactions is to convertfibrinogen, a soluble protein, to insoluble threads of fibrin. Together with platelets, the fibrin threads form a stable blood clot.
Antithrombin (AT), a serine protease inhibitor, is the major plasma inhibitor of coagulation proteases.[4] LMWHs inhibit the coagulation process through binding to AT via a pentasaccharide sequence (see also heparin: mechanism of action). This binding leads to a conformational change of AT which accelerates its inhibition of activated factor X (factor Xa). Once dissociated, the LMWH is free to bind to another antithrombin molecule and subsequently inhibit more activated factor X. Unlike AT activated by Heparin, AT activated by LMWH cannot inhibit thrombin, but can only inhibit clotting factor Xa.
Market information:
The dominant low molecular weight heparin is sanofi-aventis’s Lovenox, with the broadest label and largest clinical trial database. With limited competition, sales reached $4 billion in 2009, declining slightly in 2010 to $3.9 billion. Lovenox is indicated for the prevention of post-surgical DVT, the prevention of DVT in medical patients, treatment of DVT with or without PE, prevention of morbidity and mortality subsequent to unstable angina with non-Q wave MI, and treatment of STEMI patients receiving thrombolysis and being managed medically or with PCI. Numerous trials have demonstrated the superiority of Lovenox over unfractionated heparin in each of these settings, including Synergy, ExTRACT-TIMI25, Prevail and ExClaim.
The patents of LMWHs are expiring. Therefore, generic, or biosimilar, LMWHs are being produced by several companies. The first generic was approved by the Food and Drug Administration in July 2010. FDA has used 5 analytical and pharmacological criteria to establish the authenticity of a generic LMWH, without requiring clinical studies in patients. 
The European Medicines Agency considers LMWHs as biological products in nature consisting of not fully characterised polysaccharide mixtures. Therefore the EMA requires that the efficacy and safety of a biosimilar LMWH candidate be established in a clinical trial with patients at high risk for thromboembolism. 
Currently there are five different products (35 various strengths), manufactured by five different companies on market.
The major LMWH is Enoxaparin.  
Enoxaparin In 1993, the US FDA approved a low molecular weight heparin called Enoxaparin, which is marketed under the trade name Lovenox, among others. We believe the US market for Enoxaparin is at its apex, as has been characterised by the launch of strong generic competition coupled with the substantial share losses of the market leader, Lovenox. Lovenox, which is manufactured by Sanofi [SAN FP, EUR57.54, Neutral], had annual sales of USD2.3bn for 2010 in the US alone.  In July 2010, Sandoz launched its generic version of Enoxaparin, followed by others in October 2011. Collectively the generic enoxaparin products have garnered annual sales of USD1.5bn in 2011, meanwhile branded Lovenox sales have shrunk by USD1.2bn to USD1.1bn in 2011According to IMS data, annual sales of Enoxaparin in the US market amounted to USD2.6bn for 2011. C
Despite the strong clinical profile, the drug is facing numerous challenges. Sales are being affected by the launch of a generic version of the drug in mid-2010, following several attempts from sanofi-aventis to prevent the FDA from approving a generic version based on the drug’s macromolecular nature. In addition, further generics are expected in the EU as well as the US, despite high regulatory hurdles for approving generic versions of this complex molecule. However, potential competition from novel oral agents, such as Pradaxa and Xarelto, could pose the biggest threat to the heparins franchise. Thomson Reuters Forecast Consensus sales indicate a decline steadily over the longer term, dipping to $2.1 billion in 2015.
Heparin is a naturally occurring polysaccharide that inhibits coagulation, the process that leads to thrombosis. 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.