The Low Molecular Weight Heparin, Tinzaparin, in Thrombosis and Beyond

Abstract

Standard unfractionated heparin (UFH) has been in clinical use for over 50 years. The commercial use of low molecular weight heparins (LMWHs) began in the mid 1980s for hemodialysis and the prophylaxis of deep vein thrombosis (DVT). Initially, the clinical development of LMWHs was concentrated on the European continent. Subsequently, LMWHs were introduced in North America as well. In the initial stages of development of these drugs only nadroparin, dalteparin and enoxaparin were used. Subsequently, several other LMWHs such as ardeparin, tinzaparin, reviparin and parnaparin were introduced. LMWHs constitute a group of important medications with total sales reaching nearly 2.5 billion dollars with expanded indications reaching far beyond the initial indications for the prophylaxis of post-surgical DVT. This review highlights the pharmacology of tinzaparin. Unlike other LMWHs, tinzaparin is prepared by enzymatic hydrolysis with heparinase, while various chemical depolymerization methods are used for the synthesis of other LMWHs. As compared with the standard heparin, LMWHs have different pharmacodynamic, and pharmacokinetic properties; they also differ in clinical benefits.

Low‐Molecular‐Weight Heparins in Thrombosis and Cancer: Emerging Links

“…These characteristics of LMWHs translate into clinical advantages, which include more convenient fixed or weight-based dosing regimens, lack of a need for laboratory monitoring, reduced lengths of stay in hospitalized patients, and potentially greater clinical efficacy (31). Consequently, a number of studies have demonstrated the cost effectiveness of LMWH therapy.…”

“…Compared with UFH, LMWHs have a reduced affinity for binding to plasma proteins and cells, resulting in more favorable pharmacokinetic and pharmacodynamic profiles as well as in potentially superior clinical utility (14,31). The greater affinity of UFH for plasma-protein binding limits its anticoagulant activity and, along with variations in plasma concentrations of heparin-binding proteins, helps explain the erratic anticoagulant response to this agent.…”

“…Different methods are used by the pharmaceutical industry to produce LMWHs, and these differences account for the variation in the compounds' physical and chemical properties (14,31,45). In particular, the degree of sulfation (charge density) varies from product to product, generating distinct pharmacokinetic and pharmacodynamic profiles for each of the agents.…”

“…The characteristics of LMWHs and UFH differ in several important respects (14,31,45,47). Compared with UFH, LMWHs have a reduced affinity for binding to plasma proteins and cells, resulting in more favorable pharmacokinetic and pharmacodynamic profiles as well as in potentially superior clinical utility (14,31).…”

25 FRAGMATIC. A randomised phase III clinical trial investigating the effect of FRAGMin® added to standard therapy in patients with lung cancer

“…Dalteparin is known to inhibit heparinase, an enzyme that is secreted by cancer cells and takes part in the degradation of the extracellular matrix. Heparinase activity correlates with the metastatic potential of mammary adenocarcinoma cells and other cell lines [34,35,[37][38][39].…”