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Thromb Haemost 2009; 102(02): 371-378
DOI: 10.1160/TH08-12-0825
Cardiovascular Biology and Cell Signalling
Schattauer GmbH

Heterogeneous pathogenic processes of thrombotic microangiopathies in patients with connective tissue diseases

Tomomi Matsuyama
1   Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, Nara, Japan
,
Masataka Kuwana
2   Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
,
Masanori Matsumoto
1   Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, Nara, Japan
,
Ayami Isonishi
1   Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, Nara, Japan
,
Shigeko Inokuma
3   Rheumatology Center, Japanese Red Cross Medical Center, Tokyo, Japan
,
Yoshihiro Fujimura
1   Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, Nara, Japan
› Author AffiliationsFinancial support: This work was supported in part by grants-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology and from the Ministry of Health, Labor and Welfare of Japan.
Further Information

Publication History

Received: 19 December 2008

Accepted after major revision: 19 April 2009

Publication Date:
22 November 2017 (online)

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Summary

To clarify the pathogenic processes of thrombotic microangiopathies (TMAs) in patients with connective tissue disease (CTD), we analysed clinical characteristics and plasma ADAMTS13 levels in 127 patients with CTD-TMAs, including patients with systemic lupus erythematosus (SLE), systemic sclerosis, polymyositis/dermatomyositis, and rheumatoid arthritis (RA), and 64 patients with acquired idiopathic thrombotic thrombocytopenic purpura (ai-TTP). Plasma levels of ADAMTS13 activity, antigen, and inhibitors were determined by enzyme immunoassays. IgG type anti-ADAMTS13 antibodies were also detected by immunoblots using purified ADAMTS13. ADAMTS13 activity was significantly decreased in CTD-TMAs, regardless of the underlying disease, but the frequency of severe deficiency (defined as <0.5% of normal) was lower in CTD-TMA patients than in ai-TTP patients (16.5% vs.70.3%,p<0.01). Severe deficiency of ADAMTS13 activity was predominantly detected in patients with RA and SLE-TMAs, and was closely associated with the presence of anti-ADAMTS13 IgG antibodies. CTD-TMA patients with severe deficiency of ADAMTS13 activity appeared to have lower platelet counts and better therapeutic outcomes. At least two phenotypic TMAs occur in patients with CTDs: a minor population with deficient ADAMTS13 activity caused by neutralising autoantibodies, and a major population with normal or moderately reduced activity. Classifying CTD-TMAs by ADAMTS13 activity may be useful in predicting the clinical course and therapeutic outcomes, as patients with moderately reduced activity are likely to have more prominent renal impairment and poor prognoses.

Keywords

Connective tissue disease - TMA - ADAMTS13 - autoantibody
 

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