When antithrombin substitution strikes back

Commercially available products used for antithrombin supplementation, for example, in extracorporeal life support, may contain latent antithrombin, a hyper-stable strongly procoagulative and anti-angiogenic residue. Latent antithrombin is associated with severe thrombosis in the critically ill. In the manufacturing process of fractionated antithrombin from plasma, heat treatment, citrate, and freeze drying speed up the transformation of native antithrombin to latent antithrombin. Manufacturers are not required to assess and report the latent antithrombin content of their products. When reported, the latent antithrombin fractions in their product range from <1% to 40% of total antithrombin compared with <3% in the healthy adult and less in children. The aims of this work were (1) to convey increased awareness to clinicians who may experience defaulted, expected effect after antithrombin supplementation in, for example, heparin anticoagulation during extracorporeal life support and (2) to urge manufacturers to assess and disclose latent antithrombin content in their products.