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Hamostaseologie 2014; 34(03): 244-248
DOI: 10.5482/HAMO-14-03-0023
Case report
Schattauer GmbH

Late onset and pregnancy-induced congenital thrombotic thrombocytopenic purpura

Schwangerschafts-induzierte Spätform der hereditären thrombotisch thrombozytopenischen Purpura bei zwei Schwestern
T. Falter
1   Department of Haematology, Oncology and Pneumology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
2   Center for Thrombosis and Haemostasis, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
4   Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
,
J. A. Kremer Hovinga
3   University Clinic of Haematology & Central Haematology Laboratory, Bern University Hospital and the University of Bern, Inselspital Bern, Switzerland
,
K. Lackner
4   Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
,
H.-G. Füllemann
5   Praxisgemeinschaft am Roten Platz, St. Gallen, Switzerland
,
B. Lämmle
2   Center for Thrombosis and Haemostasis, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
3   University Clinic of Haematology & Central Haematology Laboratory, Bern University Hospital and the University of Bern, Inselspital Bern, Switzerland
,
I. Scharrer
1   Department of Haematology, Oncology and Pneumology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
› Author AffiliationsThis study was supported by the Federal Ministry of Education and Research (BMBF 01EO1003) [TF] and by a grant of the Swiss National Science Foundation (32003B-124892) [JKH, BL]. The authors are responsible for the contents of this publication.
Further Information

Publication History

received: 26 March 2014

accepted in revised form: 26 June 2014

Publication Date:
28 December 2017 (online)

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Summary

We report on our patient (case 2) who experienced a first acute episode of thrombotic thrombocytopenic purpura (TTP) at the age of 19 years during her first pregnancy in 1976 which ended in a spontaneous abortion in the 30th gestational week. Treatment with red blood cell concentrates was implemented and splenectomy was performed. After having suffered from several TTP episodes in 1977, possibly mitigated by acetylsalicylic acid therapy, an interruption and sterilization were performed in 1980 in her second pregnancy thereby avoiding another disease flare-up. Her elder sister (case 1) had been diagnosed with TTP in 1974, also during her first pregnancy. She died in 1977 during her second pregnancy from a second acute TTP episode. Diagnosis: In 2013 a severe ADAMTS13 deficiency of <10% without detectable ADAMTS13 inhibitor was repeatedly found. Investigation of the ADAMTS13 gene showed that the severe ADAMTS13 deficiency was caused by compound heterozygous ADAMTS13 mutations: a premature stop codon in exon 2 (p.Q44X), and a missense mutation in exon 24 (p.R1060W) associated with low but measurable ADAMTS13 activity. Conclusion: Genetic analysis of the ADAMTS13 gene is important in TTP patients of all ages if an ADAMTS13 inhibitor has been excluded.

Zusammenfassung

Wir berichten von unserer Patientin (Fall 2), die 1976 im Alter von 19 Jahren ihren ersten akuten Schub einer thrombotisch thrombozytopenischen Purpura (TTP) während ihrer ersten Schwangerschaft erlitt und ihr Kind in der 30. Schwangerschaftswoche verlor. Ery-throzytenkonzentrate wurden transfundiert und eine Splenektomie vorgenommen. Nach mehreren TTP-Schüben 1977, möglicherweise partiell mitigiert durch Acetylsalicylsäure, konnte ein weiterer Schub in der zweiten Schwangerschaft 1980 durch Interruptio und Tuben ligatur verhindert werden. Ihre ältere Schwester (Fall 1) hatte 1974 während ihrer ersten Schwangerschaft auch einen akuten TTP-Schub erlitten. Sie verstarb in der zweiten Schwangerschaft 1977 in Folge ihres zweiten akuten TTP-Schubes. Diagnostik: Im Jahr 2013 wurde eine schwere ADAMTS13-Defizienz von <10% festgestellt ohne nachweisbaren ADAMTS13-Inhibitor. Die Untersuchung des ADAMTS13-Gens zeigte, dass der schwere Mangel durch zwei heterozygote ADAMTS13-Mutationen verursacht wird: ein vorzeitiges Stopp-Codon in Exon 2 (p.Q44X) und eine Punktmutation in Exon 24 (p.R1060W), die eine geringe ADAMTS13-Restaktivität zeigt. Schlussfolgerung: Die genetische Analyse von ADAMTS13 bei TTP-Patienten aller Altersgruppen ist wichtig zur korrekten Diagnose einer hereditären TTP, wenn ein ADAMTS13-Inhibitor ausgeschlossen wurde.

Keywords

Hereditary TTP - pregnancy - ADAMTS13 activity - ADAMTS13 mutation

Schlüsselwörter

Hereditäre TTP - Schwangerschaft - ADAMTS13-Aktivität - ADAMTS13-Mutationen
 

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