[Low molecular weight heparin fractions. Comparative preclinical study of various parameters]

Preliminary results of the use of heparin fractions of low molecular weight showed improved bioavailability, sustained pharmacological actions and less bleeding than with non-fractionated heparin. Although prepared by different chemical and enzymatic processes, low molecular weight heparin fractions (LMWHF) possess remarkably similar chemical properties but differ in their pharmacological activity. Significant variations have been noted in tests for anti-Xa activity using reagents of USP or European standards. A study was carried out with eight heparin fractions of low molecular weight: CY 216 and CY 222 (Choay, France), Kabi 2165 (Sweden), PK 10169 (Pharmuka, France), RD 11885 (Wyeth, USA), OP 2123 (Opocrin, Italy), ORG 10172 (Organon, low countries) and heparinase depolymerization products. Numerous biochemical and pharmacological tests were carried out. In protease generation tests these agents can exert antiprotease activity when anti-Xa and anti-IIa functional activities are totally absent: it can therefore be suggested that compounds that lack affinity for anti-III contribute to the biological activities of these agents. The LMWHF possess different profiles of platelet factor, protamine and polybrene neutralization. These agents produce platelet activation to various degrees and can produce heparins able to induce thrombocytopenia. Since heparin was chosen as reference products for LMWHF, numerous dosage problems were encountered. These agents also exhibit wide variations in hemorrhagic index in animal studies. Taking previous studies into account, these products could be improved to show a greater efficacy and safety level in clinical practice.