Neutralizing the anticoagulant activity of ultra‐low‐molecular‐weight heparins using N ‐acetylglucosamine 6‐sulfatase

Heparin has been the most commonly used anticoagulant drug for nearly a century. The drug heparin is generally categorized into three forms according to its molecular weight: unfractionated ( UF , average molecular weight 13 000), low molecular weight (average molecular weight 5000) and ultra‐low‐molecular‐weight heparin ( ULMWH , average molecular weight 2000). An overdose of heparin may lead to very dangerous bleeding in patients. Protamine sulfate may be administered as an antidote to reverse heparin's anticoagulant effect. However, there is no effective antidote for ULMWH . In the current study, we examine the use of human N‐ acetylglucosamine 6‐sulfatase ( NG 6S), expressed in C hinese hamster ovary cells, as a reversal agent for ULMWH . NG 6S removes a single 6‐ O ‐sulfo group at the non‐reducing end of the ULMWH Arixtra ® (fondaparinux), effectively removing its ability to bind to antithrombin and preventing its inhibition of coagulation factor Xa. These results pave the way to developing human NG 6S as an antidote for neutralizing the anticoagulant activity of ULMWH s.