First use of the anti‐VWF nanobody caplacizumab to treat iTTP in pregnancy

Kühne, Lucas; Völker, Linus A.; Hagmann, Henning; Hägele, Holger; Osterholt, Thomas; Eichenauer, Dennis A.; Thomas, Andreas; Breuer, Johanna; Grüttner, Berthold; Gottschalk, Ingo; Kann, Martin; Benzing, Thomas; Thevis, Mario; Müller, Annette; Brinkkoetter, Paul T.

doi:10.1111/bjh.17833

Cited by 20 publications

(17 citation statements)

References 14 publications

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“…The experience of caplacizumab in pregnancy is, as yet, limited to case reports and safety is unknown. 78 There have been foetal abnormalities reported with rituximab and therefore use during pregnancy is with caution. 77 The risk of relapse in subsequent pregnancies is high.…”

Section: Pregnancy Associated Tmamentioning

confidence: 99%

Diagnosis and treatment of thrombotic microangiopathy

Thompson

Kavanagh

2022

Int J Lab Hematology

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Thrombotic microangiopathy (TMA) is characterized by thrombocytopenia, microangiopathic haemolytic anaemia and end organ damage. TMAs have varying underlying pathophysiology and can therefore present with an array of clinical presentations.Renal involvement is common as the kidney is particularly susceptible to the endothelial damage and microvascular occlusion. TMAs require rapid assessment, diagnosis, and commencement of appropriate treatment due to the high morbidity and mortality associated with them. Ground-breaking research into the pathogenesis of TMAs over the past 20 years has driven the successful development of targeted therapeutics revolutionizing patient outcomes. This review outlines the clinical presentations, pathogenesis, diagnostic tests and treatments for TMAs.

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Section: Pregnancy Associated Tmamentioning

confidence: 99%

Diagnosis and treatment of thrombotic microangiopathy

Thompson

Kavanagh

2022

Int J Lab Hematology

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“…Although other immunosuppressive agents such as azathioprine and cyclosporine have been considered in the general immune-mediated TTP population with refractory disease, 73 there are scarce anecdotal data on its use in pregnancy for the management of immune-mediated TTP. 84 Reassuringly, these agents have been used for the management of autoimmune rheumatologic conditions in pregnancy. 85 Generally, in refractory disease unresponsive to standard treatments with maternal or fetal compromise, delivery should be considered, which would then allow the use of immunosuppressive therapy such as rituximab as well as caplacizumab.…”

Section: Management Of Thrombotic Thrombocytopenic Purpura In Pregnan...mentioning

confidence: 99%

“…The first reported use of caplacizumab in pregnancy was published in 2022 in a 36-year-old pregnant woman with a history of immune-mediated TTP and persistently detectable anti-ADAMTS13 IgG autoantibodies. 84 At 17 weeks of gestation, she developed microangiopathic hemolytic anemia and thrombocytopenia. Therapeutic plasma exchange, corticosteroids, and azathioprine were initiated.…”

Section: Management Of Immune-mediated Thrombotic Thrombocytopenic Pu...mentioning

confidence: 99%

Differentiating and Managing Rare Thrombotic Microangiopathies During Pregnancy and Postpartum

Lim

Abou‐Ismail

Branch

2022

Obstetrics &Amp; Gynecology

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The most common thrombotic microangiopathy (TMA) of pregnancy is the well-recognized syndrome of preeclampsia with hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. However, rare TMAs, including thrombotic thrombocytopenic purpura, complement-mediated hemolytic-uremic syndrome, and catastrophic antiphospholipid syndrome, may occur during pregnancy or postpartum and present with features similar to those of preeclampsia with severe features. Early recognition and treatment of these infrequently encountered conditions are key for avoiding serious maternal morbidities with long-term sequelae and possible maternal or fetal death. Differentiating between preeclampsia with severe features and these rare TMAs is diagnostically challenging as there is significant overlap in their clinical and laboratory presentation. Given the rarity of these TMAs, high-quality evidencebased recommendations on diagnosis and management during pregnancy are lacking. Using current objective information and recommendations from working groups, this report provides practical clinical approaches to diagnose and manage these rare TMAs. This report also discusses how to manage individuals with a history of these rare TMAs who are planning to conceive. To optimize favorable outcomes, a multidisciplinary approach including obstetricians, maternalfetal medicine specialists, hematologists, and nephrologists alongside close clinical and laboratory monitoring is vital.

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“…Treatment with rituximab might also be considered in case of refractory disease [ 20 ]. At present, the use of caplacizumab cannot be recommended in pregnant patients due to the proven bioavailability across the placental barrier and the lack of clinical data on potential side effects affecting the foetus [ 21 ]. For pregnant patients with cTTP in remission, the ERBP working group endorses the recommendation of the ISTH guidelines to prophylactically treat patients with plasma infusions [ 1 ].…”

Section: Chapter 7 Ttp During Pregnancymentioning

confidence: 99%

European Renal Best Practice endorsement of guidelines for diagnosis and therapy of thrombotic thrombocytopaenic purpura published by the International Society on Thrombosis and Haemostasis

Eller

Knoebl

Bakkaloğlu

et al. 2022

Nephrology Dialysis Transplantation

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Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease that is caused by severe ADAMTS-13 deficiency. Immune-mediated TTP develops due to autoantibodies against ADAMTS-13, whereas congenital TTP is caused by mutations in the ADAMTS13 gene. Diagnostic possibilities and treatment options in TTP have emerged in recent years, which prompted the International Society on Thrombosis and Haemostasis (ISTH) to publish clinical practice guidelines for the diagnosis and treatment of TTP in 2020. In this article, the European Renal Best Practice Working Group endorsed the ISTH guidelines and emphasizes a number of considerations, including the importance of rapid ADAMTS-13 activity testing, the use of rituximab and anti-von Willebrand factor therapies such as caplacizumab, that enhance the clinical applicability of the guidelines in Europe.

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First use of the anti‐VWF nanobody caplacizumab to treat iTTP in pregnancy

Cited by 20 publications

References 14 publications

Diagnosis and treatment of thrombotic microangiopathy

Diagnosis and treatment of thrombotic microangiopathy

Differentiating and Managing Rare Thrombotic Microangiopathies During Pregnancy and Postpartum

European Renal Best Practice endorsement of guidelines for diagnosis and therapy of thrombotic thrombocytopaenic purpura published by the International Society on Thrombosis and Haemostasis

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