9
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: not found
      • Article: not found

      Eculizumab in Pregnant Patients with Paroxysmal Nocturnal Hemoglobinuria

      Read this article at

      ScienceOpenPublisherPubMed
      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

          Related collections

          Most cited references 18

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

          Natural history of paroxysmal nocturnal hemoglobinuria.

          Paroxysmal nocturnal hemoglobinuria (PNH), which is characterized by intravascular hemolysis and venous thrombosis, is an acquired clonal disorder associated with a somatic mutation in a totipotent hematopoietic stem cell. An understanding of the natural history of PNH is essential to improve therapy. We have followed a group of 80 consecutive patients with PNH who were referred to Hammersmith Hospital, London, between 1940 and 1970. They were treated with supportive measures, such as oral anticoagulant therapy after established thromboses, and transfusions. The median age of the patients at the time of diagnosis was 42 years (range, 16 to 75), and the median survival after diagnosis was 10 years, with 22 patients (28 percent) surviving for 25 years. Sixty patients have died; 28 of the 48 patients for whom the cause of death is known died from either venous thrombosis or hemorrhage. Thirty-one patients (39 percent) had one or more episodes of venous thrombosis during their illness. Of the 35 patients who survived for 10 years or more, 12 had a spontaneous clinical recovery. No PNH-affected cells were found among the erythrocytes or neutrophils of the patients in prolonged remission, but a few PNH-affected lymphocytes were detectable in three of the four patients tested. Leukemia did not develop in any of the patients. PNH is a chronic disorder that curtails life. A spontaneous long-term remission can occur, which must be taken into account when considering potentially dangerous treatments, such as bone marrow transplantation. Platelet transfusions should be given, as appropriate, and long-term anticoagulation therapy should be considered for all patients.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Eculizumab for the treatment of preeclampsia/HELLP syndrome.

            Severe preeclampsia with hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome is a leading cause of maternal and neonatal morbidity and mortality worldwide. Occurrence at an extremely premature gestational age is most challenging as there are dichotomous imperatives: delivery as definitive therapy for maternal health vs. prolongation of pregnancy to avoid prematurity and associated morbidities. We describe a patient presenting with severe preeclampsia/HELLP syndrome at 26 weeks gestation that was treated with Eculizumab, a targeted inhibitor of complement protein C5, which resulted in marked clinical improvement and complete normalization of lab parameters. Pregnancy was prolonged 17 days, likely resulting in a reduction of neonatal morbidity with its associated short and long-term health care costs. Successful use of Eculizumab in this case suggests that complement inhibition may be an effective treatment strategy for severe preeclampsia/HELLP syndrome. Copyright © 2012 Elsevier Ltd. All rights reserved.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              FDA report: eculizumab (Soliris) for the treatment of patients with paroxysmal nocturnal hemoglobinuria.

              On March 16, 2007, eculizumab (Soliris; Alexion Pharmaceuticals, Inc. Cheshire, CT), a humanized monoclonal antibody that binds to the human C5 complement protein, received accelerated approval by the U.S. Food and Drug Administration for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis. Eculizumab was studied in a randomized, double-blind, placebo-controlled clinical trial in 87 RBC transfusion-dependent adult PNH patients and in a supportive single-arm study in 96 patients. The eculizumab dose was 600 mg as a 35-minute i.v. infusion administered weekly for the first 4 weeks followed by 900 mg (week 5) then 900 mg every 14 days thereafter. Hemoglobin stabilized in 21 of 43 (48.8%) eculizumab-treated patients, compared with none of 44 placebo-treated patients. Eculizumab-treated patients required significantly fewer RBC transfusions than placebo-treated patients (median, 0 versus 10 units). There was also a significant reduction in the serum lactate dehydrogenase area under the curve with eculizumab compared with placebo treatment. Results of the phase II supportive study were similar to those of the phase III study. The safety database included 196 adult patients with PNH. Significant findings included the development of human anti-human antibody responses in three patients and serious meningococcal infections in three patients. Patients should undergo meningococcal vaccination at least 2 weeks prior to receiving the first eculizumab treatment and have revaccination according to current medical guidelines. Patients must be monitored and evaluated immediately for early signs of meningococcal infections and treated with antibiotics as indicated.
                Bookmark

                Author and article information

                Journal
                New England Journal of Medicine
                N Engl J Med
                New England Journal of Medicine (NEJM/MMS)
                0028-4793
                1533-4406
                September 10 2015
                September 10 2015
                : 373
                : 11
                : 1032-1039
                Article
                10.1056/NEJMoa1502950
                26352814
                © 2015
                Product

                Comments

                Comment on this article