ADAMTS13 content in plasma‐derived factor VIII/von Willebrand factor concentrates

Abstract

Thrombotic thrombocytopenic purpura (TTP) is a microangiopathy syndrome caused by a congenital or acquired deficiency of ADAMTS13, a plasma metalloprotease that cleaves von Willebrand factor (VWF) and thus prevents the formation of platelet-rich thrombi in the microcirculation. TTP can be fatal if not appropriately and timely treated with the infusion of fresh frozen plasma (FFP) or exchange plasmapheresis, that reverse the process of microangiopathy by removing anti-ADAMTS13 autoantibodies and replacing functional ADAMTS13. The treatment of TTP with FFP is not free from risks and must be administered in hospitals or clinics, owing to the substantial amount of plasma volume infused or exchanged and the frequent need of catheter application. Moreover, most FFPs are not subjected to treatments to remove or inactivate blood-borne infectious agents. A number of recent reports indicate that certain plasma-derived VWF-factor VIII (FVIII) concentrates are clinically effective in the treatment of congenital TTP. In this study, we measured ADAMTS13 levels in various plasma-derived VWF-FVIII concentrates, showing that Koate V R -DVI (Grifols), contained relatively high amounts of ADAMTS13 and that Alphanate V R (Grifols) was the closest other product in terms of protease content. Koate V R -DVI contains, on average (five lots tested), 0.091 6 0.007 Units of ADAMTS13 activity per IU of FVIII. On the basis of this analysis and other reports of VWF-FVIII concentrate utilization in congenital TTP, potential dosing, and future clinical developments are discussed. Am. J.

Management of thrombotic thrombocytopenic purpura without plasma exchange: the Jehovah’s Witness experience

“…11 Koate, to provide ADAMTS13, 3,4 would be repeated while thrombocytopenia persists. Erythropoietin and folic acid would be given to provide support for erythropoiesis.…”

“…Koate (Koate-DVI, antihemophilic factor [human]; Kedrion Biopharma) was given to provide ADAMTS13. 3,4 Koate contains factor VIII and von Willebrand factor; it is primarily used for treatment of hemophilia A and von Willebrand disease. After day 5, she progressively recovered with no further neurologic symptoms (except hallucinations attributed to corticosteroids, which were treated with risperidone).…”

Recombinant ADAMTS-13: first-in-human pharmacokinetics and safety in congenital thrombotic thrombocytopenic purpura

“…Some intermediatepurity FVIII:VWF concentrates have been shown to contain low levels of ADAMTS-13 and have been used as an alternative treatment in select patient populations. 23 Although the half-life of infused plasma ADAMTS-13 was found to be 2 to 4 days, 24 prophylaxis with 10 to 15 mL plasma /kg BW every 2 to 3 weeks has been shown to be effective in preventing acute episodes in the majority of patients with TTP. 6,25,26 Although the treatment of TTP via plasma infusions is generally effective, the therapy is frequently complicated by allergic and anaphylactic reactions or volume overload.…”

Congenital and acquired ADAMTS13 deficiency: Two mechanisms, one patient

“…Plasma ADAMTS13 activity and antigen were measured using a modified FRETS‐VWF73 assay and ELISA , respectively. Anti‐ADAMTS13 antibodies were measured by Western blotting and ELISA, with characterization of immunoglobulin classes and subclasses .…”