Comparison of Seven Generic Enoxaparins with Lovenox® on In Vitro Cross-Reactivity with Antibodies From Heparin Induced Thrombocytopenia.

Abstract

AbstractAbstract 1105 Introduction:Heparin induced thrombocytopenia (HIT) is the major complication of heparin treatment but is less frequent in patients treated with low molecular weight heparins (LMWHs) than with unfractionated heparin (UFH). Cross immunological reactions of LMWHs with HIT antibodies from patients treated with UFH is a common finding. The immunological profile is among the criteria for similarity of a generic LMWHs. The cross reactivity of generic LMWHs with HIT antibodies has yet to be compared with the innovator product. Aim:To compare the profile of platelet aggregation induced by HIT antibodies in the presence of Lovenoxâ or seven generic enoxaparins. Methods:Platelet activation by HIT antibodies in the presence of UFH (Héparine Choay, France), branded enoxaparin (Lovenox®) and 7 generics (Novex®, Enoxa®, Dilutol®, Versa®, Cutenox®, Loparin®, Fibrinox®) was assessed by Multiple Electrode Aggregometry (MEA, Multiplate, Dynabyte, Germany) according to previously published assay1. Briefly, whole blood (340 μl) from 5 individual healthy donors was incubated with pooled platelet poor plasma (200 μl) from well characterised HIT positive patients and 40 μl of UFH or Lovenox® or generic enoxaparins yielding a final concentration of 1 anti-Xa IU/ml. Platelet aggregation was recorded over 15 min and the area under the curve (AUC, AU*min) was determined. Results:UFH and branded enoxaparin showed high cross reactivity with HIT antibodies in 4 out of 5 experiments. All of the 7 generic enoxaparins gave also a high positive cross-reactivity but the intensity of platelet aggregation varied. The magnitude of the response was classified as follows: Versa® > Enoxa® > Lovenox® > Novex® > Fibrinox® > Cutenox® > Loparin® > Dilutol®. In one experiment Lovenox® showed border-line cross-reactivity with HIT antibodies. Among generic enoxaparins Versa® showed the same extent of cross reactivity as that of Lovenox®. The other generic enoxaparins did not cross react with HIT antibodies. Conclusions:This is the first study that provides key data on the comparison of in vitro cross reactivity with HIT antibodies of generic enoxaparins versus Lovenox®. In the presence of a cross-reactivity of the originator enoxaparin with heparin-PF4-IgG immune complex, there is also a cross-reactivity of the 7 studied generic enoxaparins. The intensity of cross-reactivity is an additional criterion for comparison of generic LMWHs and the originator one. The differences on the intensity of cross reactivity follow the same pattern in the case of border line cross reactivity of the originator enoxaparin.