Recombinant ADAMTS13 treatment in a pregnant patient with hereditary thrombotic thrombocytopenic purpura

Introduction Thrombotic thrombocytopenic purpura (TTP) can be difficult to diagnose. Gold standard treatment to date is plasma-based with or without immunosuppresssion depending on the absence or presence of autoantibodies in hereditary and acquired forms. We describe the first compassionate use case of recombinant ADAMTS13 (rADAMTS13) therapy in a pregnant patient with hereditary TTP (hTTP) who had previously suffered 2 ischemic strokes and one intra-uterine fetal death.

Method Diagnostic tests were performed in the Swiss reference laboratory. Diagnosis was elaborated at the Center for perioperative Thrombosis and Hemostasis as a second opinion. Treatment was provided at the Hirslanden Klinik in Zurich.

Results The hTTP diagnosis was based on the current and previous clinical events, the evolution of platelet count, and ADAMTS13 activity levels of <5%, the absence of an inhibitor and the presence of two previously described mutations. Plasmapheresis was performed as an emergency procedure and on a daily basis. The pregnant patient suffered relevant side effects. Despite this therapy, ADAMTS13 activity and platelet count did not adequately rise. R-ADAMTS13 was requested under a compassionate use indication. The request was granted by Takeda. Following cantonal approval rADAMTS13 could be imported and administered at the Hirslanden Klinik in Zurich.

Under weekly application of 40 IU/kg of bodyweight, ADAMTS13 activity could be restituted with favorable development of the platelet count. The fetus' body weight had dropped below the 3rd percentile. Maternal and fetal conditions were stabilized under rADAMTS substitution. After a single booster dose of 20 IU/kg bw, Cesarean section in the 37th week of gestation delivered a low for gestational age boy who subsequently developed very favorably. Current substitution at 40 IU/kg bw continues every other week. Mother and child are currently very well.

Conclusion We hypothesize that it was the possibility to administer larger amounts of ADAMTS13 with the recombinant drug than by plasmapheresis which was crucial to overcome the acute TTP episode and prevent imminent fetal demise in our patient. The close interprofessional and interdisciplinary interaction of nursing teams, midwives, different medical specialists as well as the team at the pharmaceutical company producing rADAMTS13 were vital to the case and permitted a fast diagnosis, emergency treatment and eventually compassionate use of rADAMTS13. The case represents the successful treatment of an acute, persistent and plasma-refractory episode with rADAMTS13 in a hTTP patient.

Publication History

Article published online:
20 February 2023