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Hereditary TTP/Upshaw–Schulman syndrome: the ductus arteriosus controls newborn survival

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Abstract

Hereditary TTP (hTTP), termed Upshaw–Schulman syndrome, is an ultra-rare disorder caused by a severe deficiency of plasma ADAMTS13 activity that allows circulation of ultra-large von Willebrand factor (UL-VWF) multimers. The greatest risk for hTTP is in their first days after birth, when 35–50% of patients will have severe hemolysis, jaundice, and thrombocytopenia. It is often fatal without effective treatment. In utero, fetal blood flowing from the pulmonary artery through the ductus arteriosus (DA) to the aorta is under low-shear-force. At birth, blood flow through the DA reverses to a left-to-right shunt, and the diameter of the DA begins to decrease due to hyper-oxygenated blood and decreased plasma prostaglandin E2. This causes turbulent circulation that unfolds UL-VWF, allowing platelet aggregation. If the DA closes promptly, hTTP newborns survive, but if it remains patent, turbulent circulation persists, triggering microvascular thrombosis. hTTP is commonly diagnosed as hemolytic disease of the fetus and newborn (HDFN) caused by anti-red cell antibodies and treated with exchange blood transfusion, which prevents kernicterus even when the diagnosis of hTTP is missed. The diagnosis of newborn-onset hTTP should be considered because HDFN does not cause severe thrombocytopenia, which might be effectively treated with recombinant ADAMTS13.

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Acknowledgements

The author acknowledges to Prof. James N. George of University of Oklahoma Health Science Center and Prof. Bernhard Lämmle of University Bern for their critical reading of this manuscript. The author also thanks to Dr. Saori Tanabe of Nihonkai General Hospital, Drs. Yoshihiko Sakurai and Tomoya Hayashi of Japanese Red Cross Kinki Block Blood Center, and Drs. Ayami Isonishi and Kazuya Sakai, and Prof. Masanori Matsumoto of Nara Medical University for collecting the data for this manuscript.

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  1. Department of Blood Transfusion Medicine, Nara Medical University, Shijyo-Cho 840, Kashihara, Nara, Japan

    Yoshihiro Fujimura

  2. Japanese Red Cross Kinki Block Blood Center, Ibaraki, Osaka, Japan

    Yoshihiro Fujimura

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Correspondence to Yoshihiro Fujimura.

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This project had no outside support. YF receives a patent royalty for ADAMTS13-act-ELISA from Alfresa Pham. (Japan).

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Fujimura, Y. Hereditary TTP/Upshaw–Schulman syndrome: the ductus arteriosus controls newborn survival. Int J Hematol (2024). https://doi.org/10.1007/s12185-024-03731-1

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