16
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Clinical Efficacy and Safety Profile of Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura

      review-article
      1 , , 1 , 2
      ,
      Cureus
      Cureus
      caplacizumab, acquired thrombotic thrombocytopenic purpura, ttp

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Thrombotic thrombocytopenic purpura (TTP) is usually defined as microangiopathy characterized by low platelet count and low red blood cell count, i.e., hemolytic anemia. It can either be acquired or immune-mediated. TTP requires quick diagnostic identification and emergent management. According to the evidence-based guidelines, the recommended therapy is plasma exchange and immunosuppression. Caplacizumab is used alongside the standard recommended therapy. Caplacizumab is a monoclonal antibody (Mab) that binds to von Willebrand factor (VWF). This prevents A1 VWF to bind platelet glycoprotein 1b receptor. The recommended dosage for this drug is 10mg. At the start, 10mg intravenous (IV) dose is given before plasma exchange, followed by daily 10mg subcutaneous (SC) dose after plasma exchange. Moreover, the SC dose is continued even after the daily plasma exchange is stopped. This review aims to consolidate findings related to the efficacy of this recently approved drug. 

          Related collections

          Most cited references24

          • Record: found
          • Abstract: found
          • Article: not found

          Improved survival in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Clinical experience in 108 patients.

          Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, fever, central nervous system abnormalities, and renal dysfunction. In early reports the mortality approached 100 percent. A treatment protocol was introduced in 1979 for patients admitted to Johns Hopkins Hospital with the diagnosis of TTP-HUS. Treatment regimens included 200 mg of prednisone a day, for patients with minimal symptoms and no central nervous system symptoms, and prednisone plus plasma exchange, for patients with rapid clinical deterioration who did not improve after 48 hours of prednisone alone and for patients presenting with central nervous system symptoms and rapidly declining hematocrit values and platelet counts. A total of 108 patients were treated, and 91 percent survived. Prednisone alone was judged to be effective in 30 patients with mild TTP-HUS (two relapses and two deaths). Plasma exchange plus prednisone was given to 78 patients with complicated TTP-HUS, resulting in 67 relapses and 8 deaths. Relapses occurred in 22 of 36 patients given maintenance plasma infusions. Neither splenectomy nor treatment with aspirin and dipyridamole was effective in those with a poor response to plasma exchange. None of the 71 patients tested had positive cultures for O157:H7 Escherichia coli. Nine percent of the patients were pregnant, and none gave birth to infants with TTP-HUS. Effective treatment with 91 percent survival is available for patients with TTP-HUS.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            Predictive Features of Severe Acquired ADAMTS13 Deficiency in Idiopathic Thrombotic Microangiopathies: The French TMA Reference Center Experience

            Severe ADAMTS13 deficiency occurs in 13% to 75% of thrombotic microangiopathies (TMA). In this context, the early identification of a severe, antibody-mediated, ADAMTS13 deficiency may allow to start targeted therapies such as B-lymphocytes-depleting monoclonal antibodies. To date, assays exploring ADAMTS13 activity require skill and are limited to only some specialized reference laboratories, given the very low incidence of the disease. To identify clinical features which may allow to predict rapidly an acquired ADAMTS13 deficiency, we performed a cross-sectional analysis of our national registry from 2000 to 2007. The clinical presentation of 160 patients with TMA and acquired ADAMTS13 deficiency was compared with that of 54 patients with detectable ADAMTS13 activity. ADAMTS13 deficiency was associated with more relapses during treatment and with a good renal prognosis. Patients with acquired ADAMTS13 deficiency had platelet count <30×109/L (adjusted odds ratio [OR] 9.1, 95% confidence interval [CI] 3.4–24.2, P<.001), serum creatinine level ≤200 µmol/L (OR 23.4, 95% CI 8.8–62.5, P<.001), and detectable antinuclear antibodies (OR 2.8, 95% CI 1.0–8.0, P<.05). When at least 1 criteria was met, patients with a severe acquired ADAMTS13 deficiency were identified with positive predictive value of 85%, negative predictive value of 93.3%, sensitivity of 98.8%, and specificity of 48.1%. Our criteria should be useful to identify rapidly newly diagnosed patients with an acquired ADAMTS13 deficiency to better tailor treatment for different pathophysiological groups.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Von Willebrand factor, ADAMTS13, and thrombotic thrombocytopenic purpura.

              J Sadler (2008)
              Discoveries during the past decade have revolutionized our understanding of idiopathic thrombotic thrombocytopenic purpura (TTP). Most cases in adults are caused by acquired autoantibodies that inhibit ADAMTS13, a metalloprotease that cleaves von Willebrand factor within nascent platelet-rich thrombi to prevent hemolysis, thrombocytopenia, and tissue infarction. Although approximately 80% of patients respond to plasma exchange, which removes autoantibody and replenishes ADAMTS13, one third to one half of survivors develop refractory or relapsing disease. Intensive immunosuppressive therapy with rituximab appears to be effective as salvage therapy, and ongoing clinical trials should determine whether adjuvant rituximab with plasma exchange also is beneficial at first diagnosis. A major unanswered question is whether plasma exchange is effective for the subset of patients with idiopathic TTP who do not have severe ADAMTS13 deficiency.
                Bookmark

                Author and article information

                Journal
                Cureus
                Cureus
                2168-8184
                Cureus
                Cureus (Palo Alto (CA) )
                2168-8184
                29 July 2019
                July 2019
                : 11
                : 7
                : e5263
                Affiliations
                [1 ] Internal Medicine, King Edward Medical University / Mayo Hospital, Lahore, PAK
                [2 ] Surgery, District Headquarter Hospital, Faisalabad, PAK
                Author notes
                Muhammad Haisum Maqsood haisumbajwa@ 123456live.com
                Article
                10.7759/cureus.5263
                6764618
                f1940686-5753-4b28-b402-19c1a643f733
                Copyright © 2019, Maqsood et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 11 April 2019
                : 18 July 2019
                Categories
                Internal Medicine
                Rheumatology
                Other

                caplacizumab,acquired thrombotic thrombocytopenic purpura,ttp

                Comments

                Comment on this article