Bortezomib for chronic relapsing thrombotic thrombocytopenic purpura: a case report

Yates, Sean G.; Matevosyan, Karén; Rutherford, Cynthia J.; Shen, Yu-Min; Sarode, Ravindra

doi:10.1111/trf.12614

Cited by 41 publications

(28 citation statements)

References 14 publications

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“…[65][66][67][68] Shortt et al reported on a case of a woman with TTP who was refractory to PEX, prednisone, cyclophosphamide, rituximab, and NAC, despite having documented depletion of B cells within her bone marrow.…”

Section: Bortezomibmentioning

confidence: 99%

How I treat refractory thrombotic thrombocytopenic purpura

Sayani¹,

Abrams

2015

Blood

145

143

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Acquired thrombotic thrombocytopenic purpura (TTP) is characterized by thrombocytopenia and microangiopathic hemolytic anemia (MAHA) without an obvious cause, and may include fever, mild renal failure, and neurologic deficits. It is characterized by a deficiency of the von Willebrand factor (VWF) cleaving enzyme, ADAMTS13 (a disintegrin and metalloproteinase, with a thrombospondin type 1 motif, member 13), resulting in formation of microthrombi in the high sheer environment of the microvasculature. This causes microvascular occlusion, MAHA, and organ ischemia. Diagnosis is based on the presence of clinical symptoms, laboratory aberrations consistent with MAHA, decreased ADAMTS13 activity, and possibly presence of anti-ADAMTS13 autoantibodies. Upfront treatment of acute TTP includes plasma exchange and corticosteroids. A significant number of patients are refractory to this treatment and will require further interventions. There are limited data and consensus on the management of the refractory TTP patient. Management involves simultaneously ruling out other causes of thrombocytopenia and MAHA, while also considering other treatments. In this article, we describe our management of the patient with refractory TTP, and discuss use of rituximab, increased plasma exchange, splenectomy, and immunosuppressive options, including cyclophosphamide, vincristine, and cyclosporine. We also review recent evidence for the potential roles of bortezomib and N-acetylcysteine, and explore new therapeutic approaches, including recombinant ADAMTS13 and anti-VWF therapy. (Blood. 2015;125(25):3860-3867) Case A 25-year-old previously healthy woman presented with a 3-day history of fatigue, nausea, abdominal pain, and easy bruising. She was alert, oriented, afebrile, had mild abdominal tenderness, and purpura on her extremities. Her hemoglobin was 8.4 g/dL; platelets, 15 3 10 9 /L; creatinine, 1.1 mg/dL; and her lactate dehydrogenase and reticulocytes were increased. Schistocytes and nucleated red blood cells were easily seen on her peripheral blood smear. In the absence of other obvious precipitators of thrombocytopenia and microangiopathic hemolytic anemia (MAHA), she was diagnosed with acquired thrombotic thrombocytopenic purpura (TTP). Blood samples were sent for ADAMTS13 (a disintegrin and metalloproteinase, with a thrombospondin type 1 motif, member 13) activity and inhibitor levels, and the patient was immediately started on plasma exchange (PEX) and prednisone 1 mg/kg per day. She responded well initially, and her platelets rose to 105 000/mL on day 4. However, on day 5, she was febrile and her platelets dropped to 40 000/mL. BackgroundAcquired TTP was initially characterized by thrombocytopenia, MAHA, renal failure, neurologic deficits, and fever. However, it is now well accepted that neither renal failure nor high fevers are key diagnostic features. Thrombocytopenia and MAHA are required for diagnosis when TTP is suspected. TTP is a hematologic emergency, with a mortality of 90% if untreated. Treatment with PEX and cortico...

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Section: Bortezomibmentioning

confidence: 99%

How I treat refractory thrombotic thrombocytopenic purpura

Sayani¹,

Abrams

2015

Blood

145

143

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“…Its mechanism of action in TTP is thought to be due to the elimination of plasma cells that produce the autoantibodies against ADAMTS13. The evidence for the use of this drug is still limited to case reports35, 40, 41, 42, 43, 44, 45 and a case series37 that reported 14 cases of TTP that were refractory to PEX, steroids, and rituximab. All but one patient recovered from their acute episode of TTP.…”

Section: Bortezomibmentioning

confidence: 99%

Novel therapies in thrombotic thrombocytopenic purpura

Masias

Cataland

2018

Research and Practice in Thrombosis and Haemostasis

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Essentials The standard of care for patients with TTP remains daily plasma exchange in addition to immune suppressive therapy.Despite the improved treatment options for TTP, the acute mortality of TTP remains between 15‐20%.Caplacizumab reduces the time to platelet recovery and the exacerbation rate in acute TTP.A better understanding of the cause and treatments of long‐term complications of TTP are needed. Thrombotic thrombocytopenic purpura (TTP) is characterized by microangiopathic hemolytic anemia and a consumptive thrombocytopenia, as a result of severe deficiency of ADAMTS13. The standard of care of the acute episode is treatment with plasma exchange and immunosuppression. After the acute episode is resolved, patients face a significant risk of relapse and long‐term complications associated with significant morbidity and even mortality. Novel treatments have been under development and will be discussed in this review. Caplacizumab, a nanobody that blocks the interaction between VWF and platelets, has shown promising results in decreasing the time to recover from the acute events that will hopefully translate into long‐term clinical benefit for patients. In addition, identifying biomarkers to allow us to better predict the risk for relapse and the development of these long‐term complications in patients with TTP are a few of the challenges that require our attention moving forward.

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“…Bortezomib (Velcade) [59] A myeloma multiplex kezelésében nagy sikerrel használt proteoszóma inhibitor. A terápia az ADAMTS13-antitestet termelő plazmasejtek elpusztítását célozná, ezek ugyanis rezisztensek a hagyományos immunszuppresszív terápiára.…”

Section: A Jövő Terápiás Lehetőségeiunclassified

Egészségügyi szakmai irányelv – A thromboticus thrombocytopeniás purpura (TTP) és a haemolyticus uraemiás syndroma (HUS) kezeléséről

…¹

2017

Orvosi Hetilap

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Bortezomib for chronic relapsing thrombotic thrombocytopenic purpura: a case report

Abstract: Bortezomib may serve as an adjunct treatment in patients with acquired TTP who exhibit an incomplete response or are refractory to conventional management.

Cited by 41 publications

References 14 publications

How I treat refractory thrombotic thrombocytopenic purpura

How I treat refractory thrombotic thrombocytopenic purpura

Novel therapies in thrombotic thrombocytopenic purpura

Egészségügyi szakmai irányelv – A thromboticus thrombocytopeniás purpura (TTP) és a haemolyticus uraemiás syndroma (HUS) kezeléséről

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