Advances in the treatment of thrombotic thrombocytopenic purpura: repurposed drugs and novel agents.

Advances in the treatment of thrombotic thrombocytopenic purpura: repurposed drugs and novel agents. Expert Rev Hematol. 2020 Apr 03;: Authors: Gómez-De León A, Villela-Martínez LM, Yáñez-Reyes JM, Gómez-Almaguer D Abstract Introduction: Thrombotic thrombocytopenic purpura (TTP) is an infrequent but fatal disease. Plasma exchange and corticosteroids continue to be the mainstay of treatment; however, repurposed drugs and novel agents are emerging as efficient treatment options.Areas covered: In this review, new therapeutic developments in immune-mediated TTP including rituximab, bortezomib, N-acetylcysteine, caplacizumab, and recombinant ADAMTS13, among others, are summarized.Expert opinion: Evidence on the use of rituximab in first and second-line settings is accumulating showing promising potential for avoiding relapses in patients in remission but with low circulating levels of ADAMTS13 in a pre-emptive fashion. Other repurposed drugs such as bortezomib and N-acetylcysteine are increasingly used off-label. Recombinant ADAMTS13 is slowly emerging. Caplacizumab, a humanized anti-von Willebrand factor-directed nanobody that blocks platelet adhesion and avoids microthrombi formation, was approved by regulatory agencies based on the positive results of a phase-III clinical trial, adding a new drug to the therapeutic arsenal in TTP. PMID: 32243196 [PubMed - as supplied by publisher]
Source: Expert Review of Hematology - Category: Hematology Tags: Expert Rev Hematol Source Type: research

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ConclusionsCaplacizumab treatment was safe and effective in a child with relapsing, autoantibody-mediated TTP. With respect to this potentially life-threatening condition, the add-on use of caplacizumab represents a novel option to reduce morbidity and mortality and improve quality of life in children and adolescents with TTP.
Source: Pediatric Nephrology - Category: Urology & Nephrology Source Type: research
Authors: Picod A, Coppo P Abstract INTRODUCTION: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a life-threatening disease characterized by a severe functional deficit in the von-Willebrand cleaving protease ADAMTS13, due to autoantibody production. The once-dismal prognosis of the disease has been changed by the discovery of the dramatic efficiency of therapeutic plasma exchange (TPE). Areas covered: This review focuses on the history and recent developments in the use of TPE for iTTP with a special emphasis on the consequences for TPE practice of the recent introduction of new highly effective immu...
Source: Expert Review of Hematology - Category: Hematology Tags: Expert Rev Hematol Source Type: research
Introduction:Acquired thrombotic thrombocytopenic purpura (TTP) is caused by autoantibodies against ADAMTS13 that prevent the cleavage of von Willebrand factor and allow the growth of microvascular thrombi, causing microangiopathic hemolysis and severe thrombocytopenia. Untreated TTP is almost always fatal but plasma exchange enables ~80% of patients to survive. Those who respond often have exacerbations or relapses that require more therapy. Exacerbations and refractory TTP usually can be treated effectively by combining plasma exchange, corticosteroids, and rituximab. A typical regimen for TTP is 4 weekly doses of rituxi...
Source: Blood - Category: Hematology Authors: Tags: 311. Disorders of Platelet Number or Function: Advances in the Treatment of TTP and HIT Source Type: research
Conclusions: After normalization to time of exposure, TEAEs occuring more frequently in the caplacizumab group were epistaxis and gingival bleeding, while TTP, hypokalemia, contusion, rash, imsomnia and hypertension occurred more frequently in the placebo group. This post-hoc analysis confirms the overall good tolerability of caplacizumab for the treatment of aTTP with mucocutaneous bleeding being the most relevant risk, consistent with the mechanism of action of this drug.DisclosuresKremer Hovinga: Shire: Other: Member of Advisory Board, Research Funding; Ablynx: Other: Member of Advisory Board. Scully: Novartis: Honorari...
Source: Blood - Category: Hematology Authors: Tags: 311. Disorders of Platelet Number or Function: Poster III Source Type: research
ABSTRACT Thrombocytopenic thrombotic purpura (TTP) is a severe hemorrhagic syndrome characterized by thrombocytopenia, microangiopathic hemolytic anemia and microvascular occlusion, besides the associated symptoms that may or may not be present: fever, neurological and renal impairment. The pathophysiology involves the autoimmune or genetic deficiency of a metalloproteinases activity (ADAMTS-13), responsible for the von Willebrand Factor cleavage. The treatment is based on plasmapheresis; and in acute or recurrent cases, corticosteroids and immunosuppressants are associated. In this article, we will discuss a case report a...
Source: Jornal Brasileiro de Patologia e Medicina Laboratorial - Category: Pathology Source Type: research
SummaryThrombotic thrombocytopenic purpura (TTP), a potentially fatal clinical syndrome, is primarily caused by autoantibodies against the von Willebrand factor (VWF)‐cleaving metalloprotease ADAMTS‐13. In general, severe deficiency of plasma ADAMTS‐13 activity ( 10 IU dL−1) in a similar clinical context supports an alternative diagnosis such as atypical hemolytic uremic syndrome (aHUS) or other types of TMA. Prompt differentiation of TTP from other causes of TMA is crucial for the initiation of an appropriate therapy to reduce morbidity and mortality. Although plasma infusion is often sufficient...
Source: Journal of Thrombosis and Haemostasis - Category: Hematology Authors: Tags: Review Article Source Type: research
This article is protected by copyright. All rights reserved. PMID: 28662310 [PubMed - as supplied by publisher]
Source: Thrombosis and Haemostasis - Category: Hematology Authors: Tags: J Thromb Haemost Source Type: research
This article is protected by copyright. All rights reserved.
Source: Journal of Thrombosis and Haemostasis - Category: Hematology Authors: Tags: Review Article Source Type: research
CONCLUSION: Our results indicate that PLT transfusions are harmful for aTTP patients when the definite diagnosis of severe ADAMTS13 deficiency is delayed. If it can be done as soon as possible, PLT transfusions for severe bleeding or surgical interventions might be allowed with subsequent plasmapheresis. PMID: 28500622 [PubMed - as supplied by publisher]
Source: Transfusion - Category: Hematology Authors: Tags: Transfusion Source Type: research
We present here a 63-year old woman with a long history of immune thrombocytopenia. She was hospitalized for a traumatic intracranial hemorrhage with thrombocytopenia. Following inefficient treatment of four platelet transfusions, immunoglobulins, and corticosteroids, we initiated treatment with a thrombopoietin (TPO) receptor agonist (eltrombopag 25 mg/d) with a good efficacy. Her mother and sister also had chronic thrombocytopenia. Clinical history, hemostasis results, and gene analysis revealed von Willebrand disease (VWD) type 2B with the mutation (c.3946G>A; p.V1316M), which combines a von Willebrand factor defect ...
Source: Platelets - Category: Hematology Tags: Platelets Source Type: research
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