Supplementary Therapeutic Recommendations
We read the review article by Bommer et al. with great interest (1). The authors provided a comprehensive and excellent overview of the different forms of microangiopathies with a focus on adulthood. As they rightly state, hereditary forms—such as atypical hemolytic-uremic syndrome (HUS) and severe hereditary ADAMTS13 deficiency—are very rare. A definite diagnosis of Upshaw-Schulman syndrome (USS) has been possible only since the beginning of the millennium, since the discovery of von-Willebrand-factor–cleaving protease (ADAMTS13). The diagnosis is hampered by the fact that some patients present with non-specific symptoms (2). A diagnostic window opens up in the neonatal period, when some USS patients may present with thrombocytopenia or hyperbilirubinemia. When the typical causes for that are ruled out, USS should be kept in mind. The relevant tests for ADAMTS13 activity have become readily available in the meantime.
We wish to add therapeutic recommendations for hereditary ADAMTS13 deficiency. In the authors’ view, plasmapheresis is indicated in this setting, as it is for the acquired form via ADAMTS13 antibodies. For the latter, plasmapheresis is absolutely indicated because the main objective is a reduction in the causative ADAMTS13 antibodies. In our experience, however, for USS, merely supplying ADAMTS13 by means of one or two transfusions of 20 mL/kg bodyweight (KG) of plasma at an interval of 12–24 h is almost always sufficient, because as a rule, ADAMTS13 antibodies are not present. This measure is also more readily available than plasmapheresis, which imposes enormous logistical and time burdens on patients and staff.
A substantial therapeutic improvement for USS in future will be recombinant ADAMTS13 concentrate, which is currently being studied in clinical trials.
Dr. med. Wolf-Achim Hassenpflug
Prof. emer. Dr. rer. nat. Reinhard Schneppenheim
Conflict of interest statement
Dr Hassenpflug received consultancy fees and study support (third party funding) for participating in clinical studies of recombinant ADAMTS13 from Shire.
Prof Schneppenheim received fees for consultancy services and lectures, and financial support (third party funding) for conducting molecular genetic studies in the context of recombinant ADAMTS13 registration trials from Shire.
|1.||Bommer M, Wölfle-Guter M, Bohl S, Kuchenbauer F: The differential diagnosis and treatment of thrombotic microangiopathies. Dtsch Arztebl Int 2018; 115: 327–34 VOLLTEXT|
|2.||Hassenpflug WA, Budde U, Schneppenheim S, Schneppenheim R: Inherited thrombotic thrombocytopenic purpura in children. Semin Thromb Hemost 2014; 40: 487–92 CrossRef MEDLINE|