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. 2023 Nov;118(5):529-546.
doi: 10.1007/s12185-023-03657-0. Epub 2023 Sep 10.

Diagnostic and treatment guidelines for thrombotic thrombocytopenic purpura (TTP) in Japan 2023

Masanori Matsumoto  1 , Yoshitaka Miyakawa  2 , Koichi Kokame  3 , Yasunori Ueda  4 , Hideo Wada  5 , Satoshi Higasa  6 , Hideo Yagi  7 , Yoshiyuki Ogawa  8 , Kazuya Sakai  9 , Toshiyuki Miyata  10 , Eriko Morishita  11 , Yoshihiro Fujimura  9 ; For TTP group of Blood Coagulation Abnormalities Research Study Team, Research on Rare and Intractable diseases, Health and Labour Sciences Research Grants from the Ministry of Health, Labour and Welfare of Japan
Affiliations

Diagnostic and treatment guidelines for thrombotic thrombocytopenic purpura (TTP) in Japan 2023

Masanori Matsumoto et al. Int J Hematol. 2023 Nov.

Abstract

Thrombotic thrombocytopenic purpura (TTP) can rapidly become a life-threatening condition, and the importance of its appropriate diagnosis and treatment cannot be overstated. Until recently, TTP has mainly been diagnosed by clinical findings such as thrombocytopenia and hemolytic anemia. In addition to these clinical findings, however, reduced activity of a disintegrin-like and metalloprotease with thrombospondin type 1 motif 13 (ADAMTS13) below 10% has become internationally accepted as a diagnostic criterion for TTP. TTP is classified as immune-mediated TTP (iTTP) if the patient is positive for anti-ADAMTS13 autoantibodies, and as congenital TTP (cTTP) if ADAMTS13 gene abnormalities are detected. Fresh frozen plasma (FFP) transfusion is performed in patients with cTTP to supplement ADAMTS13. Plasma exchange therapy using FFP is conducted in patients with iTTP to supplement ADAMTS13 and to remove both anti-ADAMTS13 autoantibodies and unusually large von Willebrand factor (VWF) multimers. To suppress autoantibody production, corticosteroid therapy is administered in conjunction with plasma exchange. The monoclonal anti-CD-20 antibody rituximab is effective in patients with iTTP. In addition, caplacizumab, an anti-VWF A1 domain nanobody, has a novel mechanism of action, involving direct inhibition of platelet glycoprotein Ib-VWF binding. The recommended first-line treatments of iTTP in Japan are plasma exchange and corticosteroids, as well as caplacizumab.

Keywords: ADAMTS13; TMA; TTP.

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Conflict of interest statement

Masanori Matsumoto received consultant/advisor fees from Sanofi, Takeda Pharmaceutical, Alexion Pharma, and Chugai Pharmaceutical; patent royalties from Alfresa Pharma; research funds from Sanofi and Alexion Pharma; lecture fees from Sanofi, Takeda Pharmaceutical, and Alexion Pharma; and scholarship donations from Chugai Pharmaceutical and Asahi Kasei Pharma. Yoshitaka Miyakawa received medical consultant fees from Zenyaku Kogyo Argenx SE, research funds from Chugai Pharma, Alexion Pharma, Sanofi, Pfizer, Novo Nordisk and Janssen, and lecture fees from Chugai Pharmaceutical, Alexion Pharma, and Sanofi. Koichi Kokame received patent royalties from Kainos, Peptide Institute, and Werfen. Yasunori Ueda received consultant/advisor fees from Sanofi and Otsuka Pharmaceutical, and lecture fees from Sanofi and Japan Blood Products Organization. Hideo Wada declares no conflicts of interest associated with this manuscript. Satoshi Higasa received lecture fees from Sanofi, Takeda Pharmaceutical, CSL Behring, Novo Nordisk Pharma, and Chugai Pharmaceutical; and scholarship donations from Chugai Pharmaceutical. Hideo Yagi declares no conflicts of interest associated with this manuscript. Yoshiyuki Ogawa received lecture fees from Chugai Pharmaceutical and scholarship donations from Bayer Yakuhin. Kazuya Sakai received research funds from Takeda Pharmaceutical and lecture fees from Sanofi. Toshiyuki Miyata received patent royalties from Kainos, Peptide Institute, and Werfen. Eriko Morishita received lecture fees from Sanofi. Yoshihiro Fujimura received consultant/special researcher fees from Japanese Red Cross Society Kinki Block Blood Center, advisor fees from Kainos and Sysmex, patent royalties from Alfresa Pharma, and lecture fees from Alexion Pharma.

Figures

Fig. 1
Fig. 1
Diagnostic and treatment algorithm for TMA. (Asterisk) The population of patients with iTTP includes a group of patients who are negative for ADAMTS13 inhibitors but positive for ADAMTS13-binding antibodies. (Double asterisks) The term “atypical HUS” (aHUS) is sometimes used conventionally in health insurance and other documentation. TMA thrombotic microangiopathy, TTP thrombotic thrombocytopenic purpura, ADAMTS13 a disintegrin-like and metalloprotease with thrombospondin type 1 motif 13, aHUS atypical hemolytic uremic syndrome, FFP fresh frozen plasma, STEC Shiga toxin-producing Escherichia coli
See this image and copyright information in PMC

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