Non-anticoagulant and other properties of low molecular weight heparins

Author(s):  
Е.В. Ройтман ◽  
В.М. Печенников

Низкомолекулярные гепарины (НМГ) являются уникальными препаратами: образуя одну группу, объединенную антитромботическим действием, каждое МНН (международное непатентованное наименование) дополнительно предоставляет свой спектр плейотропного (неантитромботического) действия со своим профилем клинической эффективности. Из-за различий в структуре этих препаратов не следует переносить результаты, полученные с одним НМГ, на другой. Однако различия между ними не делают какой-то один НМГ лучше или хуже другого. Напротив, они позволяют выбрать если не оптимальный, то наиболее подходящий препарат для конкретного пациента. При выборе НМГ для конкретного пациента необходимо строго руководствоваться инструкцией по медицинскому применению и тщательным подбором индивидуальной дозы препарата, исходя из массы тела пациента, степени тяжести заболевания, сопутствующей патологии, а также принимая во внимание ряд других факторов. Low molecular weight heparins (LMWHs) make one pharmacological group due to their antithrombotic action, but each of their international nonproprietary names provides additionally its own spectrum of pleiotropic (non-antithrombotic) actions with a specific profile for clinical efficacy. Due to the differences in the structure of these medications the results obtained with one LMWH should not be transferred to another. However, differences between LMWHs do not make one better or worse than the other. On the contrary, it allows you to choose if not optimal then the most suitable LMWH for the patient taking into account a number of influencing factors as well.

1998 ◽  
Vol 32 (5) ◽  
pp. 588-601 ◽  
Author(s):  
Pierre Martineau ◽  
Nadine Tawil

OBJECTIVE: To compare the characteristics and clinical efficacy of low-molecular-weight heparins (LMWHs) and unfractionated heparin (UFH) in the treatment of deep-vein thrombosis (DVT). Adverse effects, dosing, and cost issues are also discussed. DATA SOURCES: A MEDLINE search (January 1984–October 1997) was used to identify pertinent French and English literature, including clinical trials and reviews on LMWHs and their use in DVT. STUDY SELECTION: Trials comparing dalteparin, enoxaparin, tinzaparin, and nadroparin with UFH were selected. As studies were numerous, only randomized trials including more than 50 patients were reviewed. Moreover, all patients studied had a first episode of symptomatic DVT confirmed by objective tests (i.e., venography, duplex ultrasonography, impedance plethysmography). Clinical efficacy and safety of LMWHs were assessed in these trials. DATA EXTRACTION: Results pertaining to venographic assessment, recurrent thromboembolism, total mortality, and bleeding complications were extracted from the selected studies. DATA SYNTHESIS: Compared with UFH, LMWHs have a longer plasma half-life, better subcutaneous bioavailability, more predictable anticoagulant response, and require less intense laboratory monitoring. Most trials demonstrate comparable effects on thrombus extension and incidence of recurrent thromboembolism. Compared with UFH, LMWHs do not alter total mortality. Although animal trials predict a lower hemorrhagic potential for LMWHs, the incidence of bleeding complications is generally similar to that observed with UFH. Outpatient management of DVT with LMWHs has shown comparable safety and efficacy with inpatient UFH use but a shorter hospital stay. CONCLUSIONS: Because LMWHs are as safe and as effective as UFH, and because of their more convenient method of administration, they can be considered valuable alternatives for the treatment of DVT. Savings generated by less intensive laboratory monitoring and the possibility of early hospital discharge and outpatient therapy may outweigh the higher acquisition cost of LMWHs.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4394-4394
Author(s):  
Debra Hoppensteadt ◽  
Angel Gray ◽  
Josephine Cunanan ◽  
Walter Jeske ◽  
Jeanine M. Walenga ◽  
...  

Abstract Abstract 4394 Most low molecular weight heparins (LMWHs) have a mean molecular weight in the range of 4–6 kDa and anti-Xa/IIa ratios of 3–6. Further depolymerization of porcine mucosal heparin results in the generation of Ultra low molecular weight heparins (ULMWHs) with a molecular weight range of 2–4 kDa with proportionately decreased anti-Xa and anti-IIa activities. Bemiparin (Rovi, Madrid, Spain) represents one such ULMWH. AVE 5026 (Sanofi-Aventis, Paris, France) is a unique ULMWH (2.5 kDa) which exhibits higher affinity to antithrombin (AT) and therefore, enhanced anti-Xa activity. Because of the compositional differences between these two agents, it was hypothesized that each of these agents will have distinct anticoagulant, antiprotease and thrombin generation effects. Each of these agents was supplemented to native whole blood. Anticoagulant activity was measured using ACT, TEG, PT, APTT, thrombin time and Heptest assays. Similar studies were carried out in plasma. Amidolytic assays were used to determine the anti-Xa and anti-IIa activities. Both agents were also tested for the interactions with heparin cofactor II (HC II) and AT and were compared in the HIT antibody screening assay using platelet aggregation. In whole blood clotting assays bemiparin showed a strong anticoagulant activity in comparison to AVE 5026. Both agents also exhibited assay dependent differences in the APTT, heptest and thrombin time assays. AVE 5026 exhibited a higher anticoagulant activity in the heptest whereas bemiparin showed a stronger anticoagulant effect in the other clot based assays. In the amidolytic anti-Xa assay, AVE 5026 showed an activity of 156U/mg compared to 86 U/mg for bemiparin. In the anti-IIa assay bemiparin showed a higher activity (10 U/mg) in comparison to AVE 5026 (3.2 U/mg). The calculated Xa/IIa ratio of AVE 5026 was > 48, whereas it was 8.6 for bemiparin. While bemiparin exhibited interactions with HC II, AVE 5026 did not show significant activity in the tested concentrations (anti-IIa – IC50: 1.10±.45 μ M and >3.44±.00 μ M, respectively). On the other hand, AVE 5026 exhibited stronger interactions with AT in comparison to bemiparin (anti-FXA – IC50: .223±.03 μ M and .894±.06 μ M, respectively). Interestingly, heparinase digestion of the two products resulted in a complete loss of anti-IIa activity, but residual anti-Xa activity was found. AVE 5026 exhibited stronger anti-Xa interactions even after heparinase digestion. In the heparin induced platelet aggregation assay at 2.5 μ g/ml, bemiparin showed a relatively higher prevalence of positive interactions with HIT antibodies, whereas AVE 5026 showed a much lower prevalence (slope; AVE 5026 compared bemiparin, p=0.012). Bemiparin exhibited greater platelet factor 4 neutralization in comparison to AVE 5026. These studies clearly demonstrate that while bemiparin behaves like a typical ULMWH, AVE 5026 behaves differently in the different assays. Moreover, the oligosaccharide composition of the two products, in terms of distribution profile structure, is also different. Therefore, AVE 5026 does not represent a typical depolymerized ULMWH and is expected to exhibit a distinct pharmacologic and clinical profile. Disclosures: Hoppensteadt: Sanofi-Aventis: Research Funding.


1993 ◽  
Vol 13 (S 01) ◽  
pp. S5-S11 ◽  
Author(s):  
Debra Hoppensteadt ◽  
Jeanine Walenga ◽  
A Ahsan ◽  
O Iqbal ◽  
W Jeske ◽  
...  

SummaryThe introduction of low molecular weight heparins has added a new dimension to the pharmacological management of thrombotic disorders. Because of different chemical and pharmacological characteristics, due to the manufacturing process, each LMWH should be considered as a distinct entitity and only be used for its given indication. A list of commercially available LMWHs is included. The mechanism of action of the LMWHs and their use in various disorders are discussed. Available laboratory tests for monitoring LMWHs are presented and their limitations pointed out.


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