Defective α2antiplasmin cross-linking and thrombus stability in a case of acquired factor XIII deficiency

Joanne L Mitchell, Sonja Wright, Sajida Kazi, Henry G. Watson, Nicola J. Mutch

Research output: Contribution to journalArticle

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Abstract

Acquired factor XIII (FXIII) deficiency is a rare and life-threatening condition that is often misdiagnosed or missed completely. A 72-year-old woman presented with symptoms of major unprovoked bleeding but routine coagulation screening tests and platelet count were normal. Low activated FXIII (FXIIIa) activity levels and abnormal urea clot stability led to diagnosis of acquired FXIII deficiency. A modified Bethesda inhibitor titre of 1.6 Bethesda units/ml indicated the presence of a FXIII inhibitor. Bleeding responded to a single dose of FXIII concentrate and immunosuppression with prednisolone induced remission. A subsequent relapse was treated with combined prednisolone and Rituximab resulting in a prolonged, ongoing remission. Here we analyse the mechanisms underlying this idiopathic case of acquired FXIII deficiency. Prospective analysis of patient plasma revealed minimal FXIIIa activity and antigen in presentation and relapse samples. Thrombi formed from these samples lysed rapidly and showed an absence of cross-linked α2AP. Western blotting revealed the presence of FXIII-B, indicating only FXIII-A and FXIII-A2B2 were affected. FXIII activity and antigen levels normalised on remission. Our data suggest the presence of inhibitor-induced clearance of FXIII from plasma. As a consequence, reduced thrombus stability was evident due to defective α2AP cross-linking, thereby explaining symptoms of excessive bleeding.
Original languageEnglish
Pages (from-to)794-799
Number of pages6
JournalBritish Journal of Haematology
Volume178
Issue number5
Early online date17 May 2017
DOIs
Publication statusPublished - Sep 2017

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Factor XIII Deficiency
Factor XIII
Thrombosis
Hemorrhage
Prednisolone
Factor XIIIa
Recurrence
Antigen Presentation
Diagnostic Errors
Platelet Count
Immunosuppression
Urea
Western Blotting
Antigens

Keywords

  • Factor XIII
  • Alpha 2 Antiplasmin
  • cross-linking
  • thrombi

Cite this

Defective α2antiplasmin cross-linking and thrombus stability in a case of acquired factor XIII deficiency. / Mitchell, Joanne L; Wright, Sonja ; Kazi, Sajida ; Watson, Henry G.; Mutch, Nicola J.

In: British Journal of Haematology, Vol. 178, No. 5, 09.2017, p. 794-799.

Research output: Contribution to journalArticle

Mitchell, Joanne L ; Wright, Sonja ; Kazi, Sajida ; Watson, Henry G. ; Mutch, Nicola J. / Defective α2antiplasmin cross-linking and thrombus stability in a case of acquired factor XIII deficiency. In: British Journal of Haematology. 2017 ; Vol. 178, No. 5. pp. 794-799.
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AB - Acquired factor XIII (FXIII) deficiency is a rare and life-threatening condition that is often misdiagnosed or missed completely. A 72-year-old woman presented with symptoms of major unprovoked bleeding but routine coagulation screening tests and platelet count were normal. Low activated FXIII (FXIIIa) activity levels and abnormal urea clot stability led to diagnosis of acquired FXIII deficiency. A modified Bethesda inhibitor titre of 1.6 Bethesda units/ml indicated the presence of a FXIII inhibitor. Bleeding responded to a single dose of FXIII concentrate and immunosuppression with prednisolone induced remission. A subsequent relapse was treated with combined prednisolone and Rituximab resulting in a prolonged, ongoing remission. Here we analyse the mechanisms underlying this idiopathic case of acquired FXIII deficiency. Prospective analysis of patient plasma revealed minimal FXIIIa activity and antigen in presentation and relapse samples. Thrombi formed from these samples lysed rapidly and showed an absence of cross-linked α2AP. Western blotting revealed the presence of FXIII-B, indicating only FXIII-A and FXIII-A2B2 were affected. FXIII activity and antigen levels normalised on remission. Our data suggest the presence of inhibitor-induced clearance of FXIII from plasma. As a consequence, reduced thrombus stability was evident due to defective α2AP cross-linking, thereby explaining symptoms of excessive bleeding.

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