ISTH guidelines for treatment of thrombotic thrombocytopenic purpura

X Long Zheng¹, Sara K Vesely², Spero R Cataland³, Paul Coppo⁴, Brian Geldziler⁵, Alfonso Iorio^{6

7}, Masanori Matsumoto⁸, Reem A Mustafa⁹, Menaka Pai⁷, Gail Rock¹⁰, Lene Russell¹¹, Rawan Tarawneh¹², Julie Valdes¹³, Flora Peyvandi^{14

15}

Affiliations

¹ Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA.
² Hudson College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
³ Department of Medicine, Ohio State University, Columbus, OH, USA.
⁴ Centre de Référence des Microangiopathies Thrombotiques, Service d'Hématologie, Hôpital Saint-Antoine, Sorbonne Université, Assistance Publique, Hôpitaux de Paris, Paris, France.
⁵ Somerset, NJ, USA.
⁶ Department of Health Research Methods, Research, and Impact, McMaster University, Hamilton, ON, Canada.
⁷ Department of Medicine, McMaster University, Hamilton, ON, Canada.
⁸ Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, Japan.
⁹ Department of Medicine, University of Kansas Mediccal Center, Kansas City, KS, USA.
¹⁰ University of Ottawa, Ottawa, ON, Canada.
¹¹ Department of Intensive Care, Copenhagen University Hospital, Copenhagen, Denmark.
¹² Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
¹³ Morristown, NJ, USA.
¹⁴ Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
¹⁵ Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.

PMID: 32914526
PMCID: PMC8091490
DOI: 10.1111/jth.15010

ISTH guidelines for treatment of thrombotic thrombocytopenic purpura

X Long Zheng et al. J Thromb Haemost. 2020 Oct.

. 2020 Oct;18(10):2496-2502.

doi: 10.1111/jth.15010. Epub 2020 Sep 11.

Authors

Affiliations

¹ Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA.
² Hudson College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
³ Department of Medicine, Ohio State University, Columbus, OH, USA.
⁴ Centre de Référence des Microangiopathies Thrombotiques, Service d'Hématologie, Hôpital Saint-Antoine, Sorbonne Université, Assistance Publique, Hôpitaux de Paris, Paris, France.
⁵ Somerset, NJ, USA.
⁶ Department of Health Research Methods, Research, and Impact, McMaster University, Hamilton, ON, Canada.
⁷ Department of Medicine, McMaster University, Hamilton, ON, Canada.
⁸ Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, Japan.
⁹ Department of Medicine, University of Kansas Mediccal Center, Kansas City, KS, USA.
¹⁰ University of Ottawa, Ottawa, ON, Canada.
¹¹ Department of Intensive Care, Copenhagen University Hospital, Copenhagen, Denmark.
¹² Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
¹³ Morristown, NJ, USA.
¹⁴ Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
¹⁵ Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.

PMID: 32914526
PMCID: PMC8091490
DOI: 10.1111/jth.15010

Abstract

Background: Despite advances in treatment options for thrombotic thrombocytopenic purpura (TTP), there are still limited high quality data to inform clinicians regarding its appropriate treatment.

Methods: In June 2018, the ISTH formed a multidisciplinary guideline panel to issue recommendations about treatment of TTP. The panel discussed 12 treatment questions related to immune-mediated TTP (iTTP) and hereditary or congenital TTP (cTTP). The panel used the Grading of Recommendations Assessment, Development, and Evaluation approach, including evidence-to-decision frameworks, to appraise evidence and formulate recommendations.

Results: The panel agreed on 11 recommendations based on evidence ranging from very low to moderate certainty. For first acute episode and relapses of iTTP, the panel made a strong recommendation for adding corticosteroids to therapeutic plasma exchange (TPE) and a conditional recommendation for adding rituximab and caplacizumab. For asymptomatic iTTP with low plasma ADAMTS13 activity, the panel made a conditional recommendation for the use of rituximab outside of pregnancy, but prophylactic TPE during pregnancy. For asymptomatic cTTP, the panel made a strong recommendation for prophylactic plasma infusion during pregnancy, and a conditional recommendation for plasma infusion or a wait and watch approach outside of pregnancy.

Conclusions: The panel's recommendations are based on all the available evidence for the effects of an individual component of various treatment approaches, including suppressing inflammation, blocking platelet clumping, replacing the missing and/or inhibited ADAMTS13, and suppressing the formation of ADAMTS13 autoantibody. There was insufficient evidence for further comparing different treatment approaches (eg, TPE, corticosteroids, rituximab, and caplacizumab, etc.), for which high quality studies are needed.

Keywords: TTP; caplacizumab; guidelines; rituximab; treatment.

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Conflict of interest statement

CONFLICTS OF INTEREST

Dr. Zheng is a speaker and consultant for Alexion, Sanofi-Genzyme, and Takeda, as well as the co-founder of Clotsolution; Dr. Vesely is a biostatistician for the Oklahoma TTP registry; Dr. Cataland is a consultant for Sanofi-Genzyme and Takeda and served on an advisory board for Alexion; Dr. Coppo is a consultant for Sanofi-Genzyme, Alexion, and Takeda; Dr. Matsumoto has received royalty interest from Alfressa Pharma; Dr. Peyvandi is a speaker for Spark Therapeutics, Sobi, Bioverativ, Grifols, Takeda, and SanofiGenzyme; Dr. Geldziler is an employee of Merck Pharmaceuticals. Dr. Iorio reports that his institution has received project-based funding via research or service agreements from Bayer, CSL, Grifols, NovoNordisk, Octapharma, Pfizer, Roche, Sanofi, Sobi, Spark, and Takeda; Dr. Pai and other authors whose names are not specifically mentioned in this section declare no conflict of interest.

References

1. Zheng XL, Vesely S, Cataland S, et al. ISTH guidelines for the diagnosis of thrombotic thrombocytopenic purpura. J Thromb Haemost. 2020. - PMC - PubMed
1. Masias C, Wu H, McGookey M, Jay L, Cataland S, Yang S. No major differences in outcomes between the initial and relapse episodes in patients with thrombotic thrombocytopenic purpura: the experience from the Ohio State University Registry. Am J Hematol. 2018;93:E73–E75. - PubMed
1. Staley EM, Cao W, Pham HP, et al. Clinical factors and biomarkers predict outcome in patients with immune-mediated thrombotic thrombocytopenic purpura. Haematologica. 2019;104:166–175. - PMC - PubMed
1. Kennedy AS, Lewis QF, Scott JG, et al. Cognitive deficits after recovery from thrombotic thrombocytopenic purpura. Transfusion. 2009;49:1092–1101. - PubMed
1. Cataland SR, Scully MA, Paskavitz J, et al. Evidence of persistent neurologic injury following thrombotic thrombocytopenic purpura. Am J Hematol. 2011;86:87–89. - PubMed

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ISTH guidelines for treatment of thrombotic thrombocytopenic purpura

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ISTH guidelines for treatment of thrombotic thrombocytopenic purpura

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Conflict of interest statement

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