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      Serum complement levels in immune thrombocytopenia: Characterization and relation to clinical features

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          Abstract

          Background

          Complement may contribute to platelet destruction in immune thrombocytopenia (ITP), but serum complement levels of ITP patients are not well defined. This study characterized C3, C4, and CH50 levels from 108 ITP patients in comparison with 120 healthy subjects.

          Methods

          Results of complement testing performed using commercially available turbidimetric immunoassays were retrospectively analyzed. Mean complement levels in patients with ITP were compared with levels from a sample of 120 healthy subjects, and subgroups of ITP patients were compared. Regression analyses evaluated for relations between low complement levels and disease severity and response to ITP treatments.

          Results

          One hundred eight patients with ITP were included. Mean C3, C4, and CH50 were significantly lower in patients with ITP compared with healthy subjects, largely driven by the 32% of patients with ITP with substantial reductions in one or more assays. Patients requiring treatment had lower mean C4 (18.1 vs 23.1 mg/dL; P = .042) and CH50 (50.4 vs 63.0 mg/dL; P = .004). Mean C3 was higher in splenectomized versus nonsplenectomized patients (120.6 vs 101.0 mg/dL; P = .035). In multivariable analyses, reduced complement did not predict treatment response to corticosteroids, intravenous immunoglobulin, or thrombopoietin receptor agonists but low C4 levels did predict more severe ITP (relative to nonsevere disease, odds ratio for severe/refractory disease: 6.28; 95% confidence interval, 0.75‐52.54; P = .090). Complement levels in patients with ITP were generally consistent over repeat measurements.

          Conclusions

          Complement levels are reduced in one‐third of patients with ITP and are associated with more severe disease. Additional study is needed to evaluate if hypocomplementemia is predictive of response to emerging complement‐directed therapies.

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          Most cited references12

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          Autoantibody-mediated complement activation on platelets is a common finding in patients with immune thrombocytopenic purpura (ITP).

          It is commonly accepted that antibody-mediated removal of platelets represents a major mechanism of platelet destruction in immune thrombocytopenic purpura (ITP). Although complement activation may participate in platelet clearance, frequency and specificity of complement activation have not yet been studied systematically in ITP.
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            Complement activation on platelets correlates with a decrease in circulating immature platelets in patients with immune thrombocytopenic purpura.

            The role of the complement system in immune thrombocytopenic purpura (ITP) is not well defined. We examined plasma from 79 patients with ITP, 50 healthy volunteers, and 25 patients with non-immune mediated thrombocytopenia, to investigate their complement activation/fixation capacity (CAC) on immobilized heterologous platelets. Enhanced CAC was found in 46 plasma samples (59%) from patients with ITP, but no samples from patients with non-immune mediated thrombocytopenia. Plasma from healthy volunteers was used for comparison. In patients with ITP, an enhanced plasma CAC was associated with a decreased circulating absolute immature platelet fraction (A-IPF) (<15 x 10(9)/l) (P = 0.027) and thrombocytopenia (platelet count < 100 x 10(9)/l) (P = 0.024). The positive predictive value of an enhanced CAC for a low A-IPF was 93%, with a specificity of 77%. The specificity and positive predictive values increased to 100% when plasma CAC was defined strictly by enhanced C1q and/or C4d deposition on test platelets. Although no statistically significant correlation emerged between CAC and response to different pharmacological therapies, an enhanced response to splenectomy was noted (P < 0.063). Thus, complement fixation may contribute to the thrombocytopenia of ITP by enhancing clearance of opsonized platelets from the circulation, and/or directly damaging platelets and megakaryocytes.
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              Health-related quality of life and burden of fatigue in patients with primary immune thrombocytopenia by phase of disease: Fatigue and Quality of Life in Patients with Primary Immune Thrombocytopenia

              The main objective of this study was to compare health-related quality of life (HRQOL) of primary immune thrombocytopenia (pITP) patients with that of general population, overall, and by patient group (i.e., newly diagnosed, persistent, and chronic patients). Fatigue was also investigated as a secondary objective. Overall, 424 adult patients were enrolled in a multicenter observational study and the control group consisted of a representative sample from the general population. Propensity score matching plus further multivariate linear regression adjustment was used to compare HRQOL outcomes between pITP patients and general population. Mean age of patients was 54 years. Of those with HRQOL assessment, 99 patients (23.6%) were newly diagnosed, 53 (12.6%) were persistent, and 268 (63.8%) were chronic pITP patients. Comparison by patient group versus their respective peers in the general population revealed greater impairments in persistent pITP patients. Persistent pITP patients reported clinically meaningful impairments in physical functioning (-15; 95% CI -24.1 to -5.8; P = 0.002), social functioning (-15.3; 95% CI -25.5 to -5.1; P = 0.004), role physical (-28.4; 95% CI -43.1 to -13.7; P < 0.001), role emotional (-23.9; 95% CI -40.1 to -7.7; P = 0.004), and mental health scales (-11.3; 95% CI -21.2 to -1.4; P = 0.026) of the SF-36 questionnaire. Higher fatigue severity was associated with lower physical and mental HRQOL outcomes. Our findings suggest that the burden of the disease and treatment might depend on the disease phase and that persistent pITP patients are the most vulnerable subgroup. Am. J. Hematol. 91:995-1001, 2016. © 2016 Wiley Periodicals, Inc.
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                Author and article information

                Contributors
                @abrahamcheloff
                hal-samkari@mgh.harvard.edu , @hannyalsamkari
                Journal
                Res Pract Thromb Haemost
                Res Pract Thromb Haemost
                10.1002/(ISSN)2475-0379
                RTH2
                Research and Practice in Thrombosis and Haemostasis
                John Wiley and Sons Inc. (Hoboken )
                2475-0379
                21 June 2020
                July 2020
                : 4
                : 5 ( doiID: 10.1002/rth2.v4.5 )
                : 807-812
                Affiliations
                [ 1 ] Division of Hematology Massachusetts General Hospital Harvard Medical School Boston MA USA
                Author notes
                [*] [* ] Correspondence

                Hanny Al‐Samkari, Division of Hematology, Massachusetts General Hospital, Zero Emerson Place Suite 118, Room 112, Boston, MA 02114, USA.

                Email: hal-samkari@ 123456mgh.harvard.edu

                Author information
                https://orcid.org/0000-0002-5489-4789
                https://orcid.org/0000-0001-6175-1383
                Article
                RTH212388
                10.1002/rth2.12388
                7354388
                32685889
                426e434e-7b76-4e14-9259-57a3ba8d9c47
                © 2020 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 27 February 2020
                : 29 March 2020
                : 08 May 2020
                Page count
                Figures: 1, Tables: 3, Pages: 6, Words: 3633
                Categories
                Brief Report
                Original Articles: Hemostasis
                Custom metadata
                2.0
                July 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.5 mode:remove_FC converted:12.07.2020

                blood platelets,complement c3,complement c4,complement hemolytic activity assay,idiopathic,immune thrombocytopenia,purpura,sutimlimab,thrombocytopenic

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