Diagnosis and treatment of cold agglutinin mediated autoimmune hemolytic anemia

Berentsen, Sigbjørn; Tjønnfjord, Geir E.

doi:10.1016/j.blre.2012.01.002

Cited by 171 publications

(270 citation statements)

References 72 publications

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“…[1][2][3][4][5] The incidence has been estimated to be 1/10 6 per year. 6,7 Anemia results from binding of monoclonal cold agglutinins, most often IgM with κ light chains, to the I antigen on the erythrocyte surface.…”

Section: Introductionmentioning

confidence: 99%

Primary cold agglutinin-associated lymphoproliferative disease: a B-cell lymphoma of the bone marrow distinct from lymphoplasmacytic lymphoma

et al. 2013

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© F e r r a t a S t o r t i F o u n d a t i o nCAD diagnosed in the time period between 1995 and 2012 were studied. There were 36 women and 18 men with an age range of 40-92 (median 73) years. All patients had a clinical history of CAD with a variable degree of anemia, a positive C3d-specific direct antiglobulin test and a cold agglutinin titer in excess of 64. Monoclonal IgM had been detected in the serum of all patients by agarose electrophoresis and immunofixation. None of the patients had lymphadenopathy or splenomegaly. Clinical follow-up ranged from 3 to 152 months, with a median follow-up of 72 months. The study was approved by the institutional and regional ethical committees. Biopsy materialArchival hematoxylin and eosin-stained sections of bone marrow trephine biopsies from the 54 patients, obtained at diagnosis, were reviewed. Fourteen biopsies were fixed in 4% formaldehyde, 18 in Bplus fixative and 22 in B5 fixative. In addition, part of the diagnostic trephine biopsy of eight patients had been snap-frozen in liquid nitrogen. Two of the patients had undergone splenectomy in an attempt to reduce hemolysis. Hematoxylin and eosin-stained archival sections of formalin-fixed splenic tissue of these patients were reviewed. ImmunohistochemistryImmunohistochemical analysis was extended or repeated whenever archival sections were not available or of bad quality. The primary antibodies and the method used for immunohistochemical analysis of the bone marrow trephine biopsies are described in the Online Supplementary Methods. Flow cytometryFlow cytometry was performed on samples from 25 patients and included a total of 46 bone marrow and 10 paired peripheral blood samples, anticoagulated with heparin and EDTA, respectively. On samples analyzed before 2011, a four-color analysis 18 and from 2011 onwards, an eight-color analysis 19 was performed with antibody combinations as described in the Online Supplementary Methods.Immunoglobulin heavy chain gene sequencing, and BCL6 and MYD88 mutation analyses DNA was extracted from frozen bone marrow trephine samples, obtained from eight patients, using the EZ1 tissue kit (Qiagen, Hilden, Germany) and from formaldehyde-fixed paraffin embedded-tissue sections from another nine patients using the QIAamp DNA FFPE tissue kit (Qiagen). Immunoglobulin heavy chain gene analysis and BCL6 intron 1 mutation analysis was only performed on DNA from frozen tissue samples whereas MYD88 mutation analysis, requiring less intact DNA, was performed on frozen and formaldehyde-fixed tissue samples.BCL6 intron 1 was amplified using three sets of overlapping polymerase chain reaction (PCR) primers covering nucleotides 24 to 790 in GenBank sequence AF191831. The primer pairs and PCR conditions are described in the Online Supplementary Methods. PCR products were sequenced and analyzed using the BLAST database.The MYD88 L265P mutation (NM_002468) was analyzed using PCR and a SNaPshot multiplex kit (Applied Biosystems). PCR primers and conditions are described in the Online Supplementary Me...

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Section: Introductionmentioning

confidence: 99%

Primary cold agglutinin-associated lymphoproliferative disease: a B-cell lymphoma of the bone marrow distinct from lymphoplasmacytic lymphoma

et al. 2013

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“…Éstas son autoanticuerpos de tipo IgM que aglutinan eritrocitos en un rango entre los 4º y 37º 2,3 . La mayoría de las veces esta hemólisis no se traduce en manifestaciones clínicas importantes 2 , sin embargo, en casos con títulos altos la hemólisis puede ser severa 18 . En general el cuadro hemolí-tico aparece durante la segunda a tercera semana posterior al inicio de la fiebre 23 .…”

Section: Discussionunclassified

“…En general el cuadro hemolí-tico aparece durante la segunda a tercera semana posterior al inicio de la fiebre 23 . El pronóstico de la enfermedad suele ser benigno, y la hemólisis remite generalmente a las 4-6 semanas 18 . La sospecha de hemólisis se sustenta principalmente en el aumento de LDH, hiperbilirrubinemia indirecta, reticulocitosis y haptoglobina baja, orientándo-nos además en este caso el hallazgo de sangre en el análisis químico de orina, pero no en el físico, lo que sugiere pigmenturia.…”

Section: Discussionunclassified

“…La observación al frotis de eritrocitos aglutinados sugiere reacción mediada por crioaglutininas. El test de Coombs directo suele ser negativo debido a que la hemó-lisis es mediada principalmente por activación del complemento 18 . En el diagnóstico diferencial debe considerarse los linfomas, infecciones por virus de Ebstein Barr, Citomegalovirus, Influenza, Varicella, y por bacterias como Legionella y Citrobacter 24 .…”

Section: Discussionunclassified

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Hemólisis, exantema, serositis. Manifestaciones extrapulmonares del Mycoplasma pneumoniae: Reporte de un caso

Cares

et al. 2014

Rev. méd. Chile

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“…In auto-immune hemolytic anemia (AIHA), patients have auto-antibodies against their own RBCs. This leads to accelerated clearance of the cells via the interaction of IgG bound to RBCs with Fcγ-receptors on phagocytes in the spleen and/or in case of auto-antibodies able to activate complement via complement receptors in the liver 6,7 . Fulminant complement activation resulting in intravascular hemolysis is rare but often fatal.…”

Section: Introductionmentioning

confidence: 99%

Methods for Quantitative Detection of Antibody-induced Complement Activation on Red Blood Cells

Meulenbroek

Wouters

2014

JoVE

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Antibodies against red blood cells (RBCs) can lead to complement activation resulting in an accelerated clearance via complement receptors in the liver (extravascular hemolysis) or leading to intravascular lysis of RBCs. Alloantibodies (e.g. ABO) or autoantibodies to RBC antigens (as seen in autoimmune hemolytic anemia, AIHA) leading to complement activation are potentially harmful and can be -especially when leading to intravascular lysis -fatal 1 . Currently, complement activation due to (auto)-antibodies on RBCs is assessed in vitro by using the Coombs test reflecting complement deposition on RBC or by a nonquantitative hemolytic assay reflecting RBC lysis [1][2][3][4] . However, to assess the efficacy of complement inhibitors, it is mandatory to have quantitative techniques. Here we describe two such techniques. First, an assay to detect C3 and C4 deposition on red blood cells that is induced by antibodies in patient serum is presented. For this, FACS analysis is used with fluorescently labeled anti-C3 or anti-C4 antibodies. Next, a quantitative hemolytic assay is described. In this assay, complement-mediated hemolysis induced by patient serum is measured making use of spectrophotometric detection of the released hemoglobin. Both of these assays are very reproducible and quantitative, facilitating studies of antibody-induced complement activation. Video LinkThe video component of this article can be found at

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Diagnosis and treatment of cold agglutinin mediated autoimmune hemolytic anemia

Cited by 171 publications

References 72 publications

Primary cold agglutinin-associated lymphoproliferative disease: a B-cell lymphoma of the bone marrow distinct from lymphoplasmacytic lymphoma

Primary cold agglutinin-associated lymphoproliferative disease: a B-cell lymphoma of the bone marrow distinct from lymphoplasmacytic lymphoma

Hemólisis, exantema, serositis. Manifestaciones extrapulmonares del Mycoplasma pneumoniae: Reporte de un caso

Methods for Quantitative Detection of Antibody-induced Complement Activation on Red Blood Cells

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