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Pregnancy-associated thrombotic thrombocytopenic purpura complicated by Sjogren's syndrome and non-neutralising antibodies to ADAMTS13: a case report.

ABSTRACT:

Background

Thrombotic thrombocytopenic purpura (TTP) is a severe and life-threatening disease. Given its heterogeneous clinical presentation, the phenotype of TTP during pregnancy and its management have not been well documented.

Case presentation

We report here a 25-year-old woman, G1P0 at 36 weeks gestation, who developed severe thrombocytopenia and anemia. She was performed an emergent caesarean section 1 day after admission because of multiple organ failure. As ADAMTS 13 enzyme activity of the patient was 0% and antibodies were identified by enzyme-linked immunosorbent assay, she was diagnosed as acquired thrombotic thrombocytopenic purpura (aTTP). Furthermore, asymptomatic primary Sjögren's syndrome was incidentally diagnosed on screening. After treatment with rituximab in addition to PEX and steroids, the activity of the ADAMTS 13 enzyme increased significantly from 0 to 100%.

Conclusions

To the best of our knowledge, this is the first case report of concomitant TTP and asymptomatic Sjögren's syndrome in a pregnant woman. It highlights the association between pregnancy, autoimmune disease, and TTP. It also emphasizes the importance of an enzyme-linked immunosorbent assay in the diagnosis and rituximab in the treatment of patients with acquired TTP.

SUBMITTER: Zhou L

PROVIDER: S-EPMC8641216 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAcquired thrombotic thrombocytopenic purpura (TTP) is an autoimmune disease in which anti-ADAMTS13 autoantibodies cause severe enzyme deficiency. ADAMTS13 deficiency causes the loss of regulation of von Willebrand factor multimeric size and platelet-tethering function, which results in the formation of disseminated microvascular platelet microthrombi. Precisely how anti-ADAMTS13 autoantibodies, or antibody subsets, cause ADAMTS13 deficiency (ADAMTS13 activity generally < 10%) has not been formally investigated.MethodsWe analysed 92 acquired TTP episodes at presentation, through treatment and remission/relapse using epitope mapping and functional analyses to understand the pathogenic mechanisms of anti-ADAMTS13 IgG.Results89/92 of TTP episodes had IgG recognising the ADAMTS13 N-terminal domains. The central spacer domain was the only N-terminal antigenic target detected. 38/92 TTP episodes had autoantibodies recognising the N-terminal domains alone; 54/92 TTP episodes also had antibodies against the ADAMTS13 C-terminal domains (TSP2-8 and/or CUB domains). Changes in autoantibody specificity were detected in 9/16 patients at relapse, suggesting a continued development of the disease. Functional analyses on IgG from 43 patients revealed inhibitory IgG were limited to anti-spacer domain antibodies. However, 15/43 patients had autoantibodies with no detectable inhibitory action and as many as 32/43 patients had autoantibodies with inhibitory function that was insufficient to account for the severe deficiency state, suggesting that in many patients there is an alternative pathogenic mechanism. We therefore analysed plasma ADAMTS13 antigen levels in 91 acquired TTP presentation samples. We demonstrated markedly reduced ADAMTS13 antigen levels in all presentation samples, median 6% normal (range 0-47%), with 84/91 patients having < 25% ADAMTS13 antigen. ADAMTS13 antigen in the lowest quartile at first presentation was associated with increased mortality (odds ratio 5.7).ConclusionsAnti-spacer domain autoantibodies are the major inhibitory antibodies in acquired TTP. However, depletion of ADAMTS13 antigen (rather than enzyme inhibition) is a dominant pathogenic mechanism. ADAMTS13 antigen levels at presentation have prognostic significance. Taken together, our results provide new insights into the pathophysiology of acquired TTP.