Therapeutic plasma exchange-free treatment for first-episode TTP: A systematic review

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Abstract

Objective

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy (TMA), and therapeutic plasma exchange (TPE) is currently the standard treatment. However, TPE sometimes cannot be implemented. The aim of this study was to systematically review patients with a first TTP episode who were treated without TPE.

Method

The PubMed, Embase, Web of Science and Cochrane Library databases were searched by two investigators independently to collect case reports and clinical studies on TTP patients treated without TPE. After removing duplicate records and records that did not meet the inclusion criteria, the patients’ data of eligible studies, including the basic characteristics, treatment regimens, and outcomes were extracted for further analysis.

Results

A total of 5338 potentially relevant original studies were identified, from which 21 studies, including 14 cases, 3 case series and 4 retrospective studies, met eligibility requirements and were included. Treatment regimens in the absence of TPE were found to vary based on individual information. Most patients recovered, with normal platelet counts and ADAMT13 activity at discharge. In the meta-analysis of retrospective studies, the TPE-free group had no higher mortality than the TPE-treated group.

Conclusion

Our study shows that TPE-free treatment may not increase the mortality of TTP patients, which provides a new treatment concept for patients with first episodes of TTP. However, the current evidence is not high due to the lack of randomized controlled trials, so more well-designed prospective clinical trials are warranted to investigate the safety and efficacy of TPE-free treatment regimens in TTP patients.

Introduction

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening thrombotic microangiopathy that predominantly affects women. Thrombospondin type 1 motif, member 13(ADAMTS13) is the proteolytic enzyme of von Willebrand factor (vWF). The pathogenesis of TTP is that ADAMTS13 deficiency leads to the accumulation of ultralarge vWF multimers, which induce excessive platelet binding and activation, and subsequent the formation of microthrombosis [1]. According to the mechanism of ADAMTS13 deficiency, TTP includes congenital TTP and acquired TTP (aTTP). It has been reported that 5.5 % of TTP patients are hereditary, and 94.5 % are acquired [2]. Congenital TTP, also known as Upshaw-Schulman syndrome, is caused by mutations in the gene encoding ADAMTS13. Plasma infusion is used to supplement the deficiency of ADAMTS13 in patients with congenital TTP [3]. In contrast, acquired autoimmune TTP refers to the presence of autoantibodies against ADAMTS13, with an annual incidence of 3–11 cases per million people [4]. Although TTP is rare and has a low incidence, it is severe and has a high mortality rate. If not identified and treated in time, the fatality rate of TTP is probably as high as 90 % [4]. After the introduction of plasma exchange, the mortality rate was reduced to 10–20 % [4]. Currently, therapeutic plasma exchange (TPE) with fresh frozen plasma (FFP) is the basic and most important treatment for TTP. TPE is performed immediately after TTP is suspected or confirmed, which replaces ultralarge vWF, ADAMDTS13 antibodies, pro-inflammatory cytokines and supplement ADAMDTS13 [4].

With the clear understanding of the pathogenesis of TTP and the conduct of clinical trials, TPE combined with glucocorticoids, immunosuppressants, and nanobodies targeting vWF has become a new strategy for TTP treatment. Especially after the application of caplacizumab (an anti-vWF domain A1 nanobody), the clinical outcome of patients is improved, such as faster normalization of the platelet count, less plasma exchange and shorter hospitalization [5], [6], [7]. However, in some cases, TPE with FFP cannot be performed in patients with TTP who cannot or will not receive it due to religious prohibitions or a history of severe plasma allergy [8], [9]. Therefore, we are considering whether the treatment of TTP can be completely without TPE. In view of this, we systematically reviewed relevant studies on the treatment of TTP without TPE, seeking to break through the traditional treatment strategy.

Section snippets

Search strategies

In this research, we conducted a systematic review of studies on the treatment of TTP without TPE. Four major databases, PubMed, Embase, Web of Science and Cochrane Library, were searched up to 15 January 2022. To avoid missing any articles, we developed an extensive search strategy using the following search terms: (thrombotic thrombocytopenic purpura OR Thrombocytopenic Purpura, Thrombotic OR Thrombotic Thrombocytopenic Purpura OR Purpura, Thrombotic Thrombopenic OR Thrombopenic Purpura,

Results

Studies on TPE-free treatment for TTP, including 14 case reports, 3 case series, and 5 retrospective studies, were eligible for analysis.

Discussion

TTP is an acute, life-threatening disease, and TPE with FFP is the cornerstone of its treatment. After the introduction of TPE in the 1990s, the mortality rate of TTP was significantly reduced [11], [12]. Subsequent studies have shown that TPE should be performed as soon as TTP is diagnosed or suspected, because delayed initiation of treatment may increase mortality [2], [13]. The infusion of FFP can trigger fever and allergic reactions in patients, which can be ameliorated by solvent/detergent

Conclusion

In summary, we mainly sorted out the relevant studies on TTP without TPE treatment and found that some patients recovered in a variety of treatment options without TPE, which suggests that TPE-free treatment may also be feasible for patients with first episodes of TTP. Although TPE has low economic cost and good clinical outcomes, investigating more treatment options will further improve the quality of life and reduce the cost-effectiveness of TTP patients.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Declaration of interest

None.

Acknowledgements

The authors have no relevant financial or non-financial interests to disclose. Bin Tan and Li Qin created a theme and provided valuable advice for this systematic review. Jiang Wang and Fu Cheng created a theme for this study, performed literature screening, collected and analyzed data, and wrote the manuscript. When there was disagreement in the screening process, Yingying Niu made the final decision. Lingli Yan and Jiaheng Li assisted with the completion of this study and provided language

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  • 1

    Jiang Wang and Fu Cheng are joint first authors. They contributed equally to this manuscript.

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