Abstract
Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease, characterized by microangiopathic hemolytic anaemia and thrombocytopenia, resulting in neurologic and/or renal abnormalities. We report a 49-year-old patient with a history of thrombotic events, renal failure, and thrombocytopenia. Blood analysis demonstrated no ADAMTS13 activity in the absence of antibodies against ADAMTS13. The complete ADAMTS13 gene was sequenced, and two mutations were identified: one mutation on exon 24 (Arg1060Asp), which had previously been described, and a mutation on exon 27 (Met1260IlefsX34), which has not been reported. For these mutations, compound heterozygosity appears to be necessary to cause TTP, as family members of the patient display only one of the mutations and all displayed normal ADAMTS13 activity.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Chapman K, Seldon M, Richards R. Thrombotic microangiopathies, thrombotic thrombocytopenic purpura, and ADAMTS-13. Semin Thromb Hemost. 2012;38:47–54.
Uchida T, Wada H, Mizutani M, et al. Identification of novel mutations in ADAMTS13 in an adult patient with congenital thrombotic thrombocytopenic purpura. Blood. 2004;104:2081–3.
Bouw MC, Dors N, van Ommen H, Ramakers-van Woerden NL. Thrombotic thrombocytopenic purpura in childhood. Pediatr Blood Cancer. 2009;53:537–42.
Loirat C, Girma JP, Desconclois C, Coppo P, Veyradier A. Thrombotic thrombocytopenic purpura related to severe ADAMTS13 deficiency in children. Pediatr Nephrol. 2009;24:19–29.
Scully M, Goodship T. How I treat trombotic thrombocytopenic purpura and atypical haemolytic uraemic syndrome. Br J Haematol. 2014;164:759–66.
Furlan M, Robles R, Morselli B, Sandoz P, Lämmle B. Recovery and half-life of von Willebrand factor cleaving protease after plasma therapy in patients with thrombotic thrombocytopenic purpura. Thromb Haemost. 1999;81:8–13.
Miyata T, Kokame K, Matsumoto M, Fujimura Y. ADAMTS13 activity and genetic mutations in Japan. Hämostaseologie. 2013;33:131–7.
Rank CU, Kremer Hovinga J, Taleghani MM, Lämmle B, Gøtze JP, Nielsen OJ. Congenital thrombotic thrombocytopenic purpura caused by new compound heterozygous mutations of the ADAMTS13 gene. Eur J Haematol. 2014;92:168–71.
Kokame K, Nobe Y, Kokubo Y, Okayama A, Miyata T. FRETS-VWF73, a first fluorogenic substrate for ADAMTS13 assay. Br J Haematol. 2005;129:93–100.
Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16:1215.
Tao Z, Anthony K, Peng Y, Choi H, Nolasco L, Rice L, et al. Novel ADAMTS-13 mutations in an adult with delayed onset thrombotic thrombocytopenic purpura. J Thromb Haemost. 2006;4:1931–5.
Majerus EM, Anderson PJ, Sadler JE. Binding of ADAMTS13 to von Willebrand Factor. J Biol Chem. 2005;280:21773–8.
Acknowledgments
Dr. C.M. Eckmann, of Sanquin Diagnostics, Amsterdam, The Netherlands, is acknowledged for analysing ADAMTS13 activity.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical standards
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. The patient and included family members gave informed consent for the present study, including the laboratory analyses and genetic analysis of the ADAMTS13 gene.
About this article
Cite this article
Krabbe, J.G., Kemna, E.W.M., Strunk, A.L.M. et al. Adult-onset congenital thrombotic thrombocytopenic purpura caused by a novel compound heterozygous mutation of the ADAMTS13 gene. Int J Hematol 102, 477–481 (2015). https://doi.org/10.1007/s12185-015-1849-2
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12185-015-1849-2