Chronic relapsing thrombotic thrombocytopenic purpura: Role of therapy with cyclosporine

Pasquale, Donald; Vidhya, Rakesh; DaSilva, Karen; Tsan, Min‐Fu; Lansing, Lawrence; Chikkappa, G.

doi:10.1002/(sici)1096-8652(199801)57:1<57::aid-ajh10>3.3.co;2-r

Cited by 14 publications

(15 citation statements)

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“…Cyclosporine has been successfully used to treat refractory TTP in case reports and in a cohort study. [49][50][51][52][53] In a study evaluating the efficacy of PEX and cyclosporine in the treatment of TTP (included refractory TTP cases), remission was achieved in 89% of all patients. 53 Although this study also showed improvement in ADAMTS13 activity and in the suppression of ADAMTS13 inhibitors, the response rates were closely similar to those achieved with PEX alone.…”

Section: Cyclosporinementioning

confidence: 99%

How I treat refractory thrombotic thrombocytopenic purpura

Sayani¹,

Abrams

2015

Blood

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: Cyclosporinementioning

confidence: 99%

How I treat refractory thrombotic thrombocytopenic purpura

Sayani¹,

Abrams

2015

Blood

143

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“…As with rituximab, case reports have suggested the effectiveness of CSA in patients with relapsing or refractory forms of TTP [35][36][37][38][39][40][41]. These case reports suggest the effectiveness of CSA in patients who are refractory or resistant to PE.…”

Section: Ciclosporinmentioning

confidence: 99%

Targeting the inhibitor of ADAMTS13 in thrombotic thrombocytopenic purpura

Cataland¹,

2007

Expert Opinion on Pharmacotherapy

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There has clearly been an evolution in the treatment of thrombotic thrombocytopenic purpura (TTP) over the past several years based upon a better understanding of the pathophysiology of this disorder. An autoantibody inhibitor of the ADAMTS13 protease and the resulting severe deficiency of ADAMTS13 function seem to be significant risk factors for the development of TTP, a disease increasingly recognized as an autoimmune disorder. Immune-based therapy aimed at suppressing the inhibitor of ADAMTS13 has been applied to the treatment of patients with TTP who are refractory to the standard treatment of plasma exchange and to patients with multiple recurrences of TTP. More recently, immunosuppressive therapy has been used alone as prophylactic therapy to prevent recurrences of acute TTP. This review focuses on the recent developments in the use of rituximab and ciclosporin in the treatment of TTP.

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“…Single cases and small series have suggested that immunomodulatory drugs such as cyclosporine A, azathioprine, and mycophenolate mofetil could have benefit in the prevention of chronic relapses in acquired TTP [60][61][62]. However, the use of these drugs in this context requires further accurate evaluation through large studies.…”

Section: Other Immunomodulatory Drugsmentioning

confidence: 99%