Biological activities of two ultra‐low molecular weight heparins, semuloparin and bemiparin, reveal that a common potency standard is inappropriate

Ultra‐low‐molecular‐weight heparins (U‐LMWHs) are being developed to improve on the safety and efficacy of antithrombotic therapy. Semuloparin and bemiparin, two agents produced by distinct manufacturing processes are considered to belong to this new class of drugs. The objective of this investgation was to determine whether a common standard could be used to define their potency. Activities were compared using typical clinical coagulation assays and pharmacological assays required for potency assessment. The activity of semuloparin and bemiparin was comparable in FXa‐based assays (anti‐FXa, Heptest). However, bemiparin produced a stronger effect in the aPTT, ACT and anti‐thrombin assays. Assessment of the parallelism of the concentration‐response curves indicated that bemiparin and semuloparin are not equivalent in terms of anti‐FIIa activity. Bemiparin had a stronger inhibitory effect on thrombin induced platelet aggregation, and a stronger interaction with HIT antibodies. These data demonstrate that the simple characteristic of molecular weight of heparin‐derived agents is insufficient to determine drug class and that biologic activities relevant to clinical safety and efficacy need to be considered as well.