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Hamostaseologie
DOI: 10.1055/a-2211-6841
Case Report

Anti-Thrombin IgA in a Patient with Multiple Myeloma Leading to In Vitro Interference in Multiple Coagulation Tests and Confounding Diagnosis

Christian Irsara 
1   Central Institute of Medical and Chemical Laboratory Diagnostics (ZIMCL), University Hospital of Innsbruck, Innsbruck, Austria
,
Andrea Griesmacher
1   Central Institute of Medical and Chemical Laboratory Diagnostics (ZIMCL), University Hospital of Innsbruck, Innsbruck, Austria
,
Lorin Loacker
1   Central Institute of Medical and Chemical Laboratory Diagnostics (ZIMCL), University Hospital of Innsbruck, Innsbruck, Austria
,
Clemens Feistritzer
2   Department of Internal Medicine V, Hematology and Oncology, Medical University of Innsbruck, Innsbruck, Austria
,
Cosima Anna Überbacher
3   Hemato-Oncological Day Hospital, Franz Tappeiner Hospital, Merano, Italy
,
Jean Amiral
4   Scientific-Hemostasis Consulting, Franconville, France
› Institutsangaben Funding Not applicable.
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Abstract

Background We report the case of a 59-year-old multiple myeloma patient in whom an anti-human thrombin IgA antibody led to prolonged in vitro coagulation times, suggesting inhibitors to all intrinsic coagulation factors in the absence of spontaneous bleeding.

Methods Routine and extensive special coagulation tests, in vivo bleeding time, and specific antibody testing were performed.

Results Although the patient did not suffer from spontaneous bleeding and had a normal in vivo bleeding time, the anti-human thrombin IgA autoantibody affected all coagulation assays involving human thrombin in vitro, mimicking inhibitors to intrinsic coagulation factors. As the IgA paraprotein and the IgA antibody virtually disappeared after autologous stem cell transplantation, the coagulation tests also largely normalized.

Conclusion Antibodies to human thrombin may interfere with all coagulation assays involving thrombin, imitating a severe coagulopathy. However, in vivo they do not necessarily lead to strongly increased bleeding tendency. Complex and ambiguous coagulation abnormalities should be evaluated and treated in an interdisciplinary setting, including a highly specialized coagulation laboratory, from the beginning.

Zusammenfassung

Wir berichten über eine 59-jährige Myelom-Patientin, die einen IgA Autoantikörper gegen humanes Thrombin entwickelt hat. Dieser führte in vitro zu verlängerten Gerinnungszeiten und täuschte Hemmkörper gegen sämtliche intrinsische Gerinnungs-Einzelfaktoren vor, wobei die Patientin keine spontane Blutungsneigung aufwies. Der Autoantikörper beeinflusste dabei alle Gerinnungstests, in welchen humanes (nicht aber bovines) Thrombin zum Einsatz kommt. Nachdem das IgA Paraprotein und somit auch der Autoantikörper nach autologer Stammzelltransplantation im Wesentlichen verschwunden war, normalisierten sich auch die Gerinnungsanalysen weitgehend. Zusammenfassend zeigt sich, dass Autoantikörper gegen humanes Thrombin zahlreiche Gerinnungstests in vitro massiv stören können ohne zwangsweise mit einer spontanen Blutungsneigung einhergehen zu müssen. Komplexe oder ungewöhnliche Konstellationen von Gerinnungsanalysen sollten von Anfang an interdisziplinär und in Zusammenarbeit mit einem hochspezialisierten Gerinnungslabor abgeklärt und behandelt werden.

Keywords

hemostasis - hemophilia - autoantibody - thrombin - multiple myeloma

Schlagwörter

Hämostase - Autoantikörper - Thrombin - Multiples Myelom

Authors' Contributions

C.I., L.L., and A.G. requested, performed and/or interpreted coagulation tests. J.A. performed and interpreted autoantibody studies. C.F., C.A.Ü. and C.I. got clinical data. C.I. and J.A. wrote the original draft. All authors read, revised, and approved the submitted version of the manuscript.


Ethical Approval

If case reports with less than five patients are fully anonymized, they do not require approval by the Ethics Commission at the Medical University of Innsbruck.


Consent to Participate

At the time of writing this manuscript, unfortunately the patient was already deceased.


Availability of Data and Materials

All relevant data are contained within the manuscript.




Publikationsverlauf

Eingereicht: 16. August 2023

Angenommen: 13. November 2023

Artikel online veröffentlicht:
01. März 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Stuttgart · New York

 

  • References

  • 1 Cowan AJ, Green DJ, Kwok M. et al. Diagnosis and management of multiple myeloma: a review. JAMA 2022; 327 (05) 464-477
    Google Scholar
  • 2 Rajkumar SV, Dimopoulos MA, Palumbo A. et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 2014; 15 (12) e538-e548
    Google Scholar
  • 3 Mrosewski I, Urbank M. Identification of paraproteins via serum immunofixation or serum immunosubtraction and immunoturbidimetric quantitation of serum immunoglobulins in the laboratory testing for monoclonal gammopathies. Arch Pathol Lab Med 2021; 145 (12) 1552-1557
    Google Scholar
  • 4 Shimanovsky A, Alvarez Argote J, Murali S, Dasanu CA. Autoimmune manifestations in patients with multiple myeloma and monoclonal gammopathy of undetermined significance. BBA Clin 2016; 6: 12-18
    Google Scholar
  • 5 Gosselin RC, Adcock DM, Bates SM. et al. International Council for Standardization in Haematology (ICSH) recommendations for laboratory measurement of direct oral anticoagulants. Thromb Haemost 2018; 118 (03) 437-450
    Google Scholar
  • 6 Barbosa ACN, Montalvão SAL, Barbosa KGN. et al. Prolonged APTT of unknown etiology: a systematic evaluation of causes and laboratory resource use in an outpatient hemostasis academic unit. Res Pract Thromb Haemost 2019; 3 (04) 749-757
    Google Scholar
  • 7 Ljung R, Auerswald G, Benson G. et al. Inhibitors in haemophilia A and B: management of bleeds, inhibitor eradication and strategies for difficult-to-treat patients. Eur J Haematol 2019; 102 (02) 111-122
    Google Scholar
  • 8 Collins PW, Hirsch S, Baglin TP. et al; UK Haemophilia Centre Doctors' Organisation. Acquired hemophilia A in the United Kingdom: a 2-year national surveillance study by the United Kingdom Haemophilia Centre Doctors' Organisation. Blood 2007; 109 (05) 1870-1877
    Google Scholar
  • 9 Knoebl P, Marco P, Baudo F. et al; EACH2 Registry Contributors. Demographic and clinical data in acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2). J Thromb Haemost 2012; 10 (04) 622-631
    Google Scholar
  • 10 Green D, Lechner K. A survey of 215 non-hemophilic patients with inhibitors to Factor VIII. Thromb Haemost 1981; 45 (03) 200-203
    Google Scholar
  • 11 Hay CR, Brown S, Collins PW, Keeling DM, Liesner R. The diagnosis and management of factor VIII and IX inhibitors: a guideline from the United Kingdom Haemophilia Centre Doctors Organisation. Br J Haematol 2006; 133 (06) 591-605
    Google Scholar
  • 12 Miller CH, Platt SJ, Rice AS, Kelly F, Soucie JM. Hemophilia Inhibitor Research Study Investigators. Validation of Nijmegen-Bethesda assay modifications to allow inhibitor measurement during replacement therapy and facilitate inhibitor surveillance. J Thromb Haemost 2012; 10 (06) 1055-1061
    Google Scholar
  • 13 Baglin TP, Langdown J, Frasson R, Huntington JA. Discovery and characterization of an antibody directed against exosite I of thrombin. J Thromb Haemost 2016; 14 (01) 137-142
    Google Scholar