title: A common standard is inappropriate for determining the potency of ultra low molecular weight heparins such as semuloparin and bemiparin.
abstract: BACKGROUND
  Lower low-molecular-weight heparins are being developed to improve on the safety and efficacy of antithrombotic therapy. Semuloparin and bemiparin are two depolymerized heparins produced by distinct manufacturing processes. The objective of this investigation was to determine whether a common standard could be used to define their potency.
  
  
  METHODS
  Activities were compared using typical clinical coagulation assays and pharmacological assays required for potency assessment.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  These data demonstrate that depolymerized heparins can exhibit a range of biologic activities making them unique agents. Pharmacopoeial parameters such as anti-IIa and anti-Xa potency and molecular weight are insufficient to characterize such agents.
authors: Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois 60153, USA.
authors: Walter P
authors: WP
authors: Jeske
authors: Debra
authors: D
authors: Hoppensteadt
authors: Angel
authors: A
authors: Gray
authors: Jeanine M
authors: JM
authors: Walenga
authors: Josephine
authors: J
authors: Cunanan
authors: Lauren
authors: L
authors: Myers
authors: Jawed
authors: J
authors: Fareed
authors: Alain
authors: A
authors: Bayol
authors: Hélène
authors: H
authors: Rigal
authors: Christian
authors: C
authors: Viskov
mesh_terms: D001323:Autoantibodies / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests / Q000592:standards*; D004305:Dose-Response Relationship, Drug; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D006495:Heparin, Low-Molecular-Weight / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D008970:Molecular Weight; D010314:Partial Thromboplastin Time / Q000592:standards; D010974:Platelet Aggregation / Q000187:drug effects; D010978:Platelet Factor 4 / Q000276:immunology; D010979:Platelet Function Tests / Q000592:standards*; D011516:Prothrombin / Q000037:antagonists & inhibitors; D012015:Reference Standards; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000378:metabolism; D014914:Whole Blood Coagulation Time / Q000592:standards
chemical_list: D001323:Autoantibodies; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D010978:Platelet Factor 4; C569346:semuloparin; D011516:Prothrombin; C025337:Factor IIa; D013917:Thrombin; C411345:bemiparin