Table 2

Guide to the differential diagnosis of hemolysis in patients after HPC transplantation

DiagnosisPathophysiologySerologic findings
HPC graft-related immune hemolysis 
    Major ABO incompatibility between HPC donor and recipient Hemolysis of transfused erythrocytes, delay in erythrocyte engraftment DAT positive for C3d, IgG, or both; anti-A and/or anti-B present in eluate 
    Minor ABO incompatibility between HPC donor and recipient Hemolysis of patient's erythrocytes caused by transfused donor's plasma or by passenger lymphocyte-derived isohemagglutinins DAT positive for C3d, IgG, or both anti-A and/or anti-B present in eluate 
    Major incompatibility: other blood group antigens Hemolysis of transfused donor's erythrocytes DAT positive for C3d, IgG, or both; antibody to non-ABO red blood cell antigen(s) identified in eluate and patient plasma 
    Minor incompatibility: other blood group antigens Hemolysis of patient's erythrocytes caused by alloantibodies in transfused donor plasma or by passenger lymphocyte-derived alloantibodies DAT positive for C3d, IgG, or both: antibody to non-ABO red blood cell antigen(s) identified in eluate and patient plasma 
Transfusion-related immune hemolysis 
    Transfusion of erythrocytes incompatible with donor or patient Hemolysis of transfused erythrocytes caused by patient's native or graft-derived antibodies DAT positive for C3d, IgG, or both: anti-A and/or anti-B or antibody to other RBC antigen identified in eluate and patient plasma 
    Transfusion of plasma incompatible with donor or patient Hemolysis of patient and/or donor erythrocytes DAT positive for C3d, IgG, or both; anti-A and/or anti-B or antibody to other RBC antigen identified in eluate and patient plasma 
Other causes of immune hemolysis 
    Autoimmune hemolytic anemia Hemolysis and serologic incompatibility of (all) crossmatched donor erythrocytes DAT positive for C3d, IgG or both; panagglutinin present in eluate and patient plasma 
    Drug-induced hemolytic anemia Autoantibody formation induced by drug, hapten mechanism, or drug modification of erythrocyte membrane DAT positive for C3d, IgG, or both; eluate may react with drug-treated erythrocytes 
Nonimmune hemolysis 
    Thrombotic thrombocytopenic purpura Microangiopathic hemolytic anemia DAT and antibody screen negative 
    Infusion of cryopreserved stem cell products Nonimmune hemolysis may be observed during infusion of DMSO-cryopreserved HPC preparations DAT negative 
    Clostridium perfringens sepsis C perfringens produces hemolysin toxins, resulting in nonimmune intravascular hemolysis DAT negative 
DiagnosisPathophysiologySerologic findings
HPC graft-related immune hemolysis 
    Major ABO incompatibility between HPC donor and recipient Hemolysis of transfused erythrocytes, delay in erythrocyte engraftment DAT positive for C3d, IgG, or both; anti-A and/or anti-B present in eluate 
    Minor ABO incompatibility between HPC donor and recipient Hemolysis of patient's erythrocytes caused by transfused donor's plasma or by passenger lymphocyte-derived isohemagglutinins DAT positive for C3d, IgG, or both anti-A and/or anti-B present in eluate 
    Major incompatibility: other blood group antigens Hemolysis of transfused donor's erythrocytes DAT positive for C3d, IgG, or both; antibody to non-ABO red blood cell antigen(s) identified in eluate and patient plasma 
    Minor incompatibility: other blood group antigens Hemolysis of patient's erythrocytes caused by alloantibodies in transfused donor plasma or by passenger lymphocyte-derived alloantibodies DAT positive for C3d, IgG, or both: antibody to non-ABO red blood cell antigen(s) identified in eluate and patient plasma 
Transfusion-related immune hemolysis 
    Transfusion of erythrocytes incompatible with donor or patient Hemolysis of transfused erythrocytes caused by patient's native or graft-derived antibodies DAT positive for C3d, IgG, or both: anti-A and/or anti-B or antibody to other RBC antigen identified in eluate and patient plasma 
    Transfusion of plasma incompatible with donor or patient Hemolysis of patient and/or donor erythrocytes DAT positive for C3d, IgG, or both; anti-A and/or anti-B or antibody to other RBC antigen identified in eluate and patient plasma 
Other causes of immune hemolysis 
    Autoimmune hemolytic anemia Hemolysis and serologic incompatibility of (all) crossmatched donor erythrocytes DAT positive for C3d, IgG or both; panagglutinin present in eluate and patient plasma 
    Drug-induced hemolytic anemia Autoantibody formation induced by drug, hapten mechanism, or drug modification of erythrocyte membrane DAT positive for C3d, IgG, or both; eluate may react with drug-treated erythrocytes 
Nonimmune hemolysis 
    Thrombotic thrombocytopenic purpura Microangiopathic hemolytic anemia DAT and antibody screen negative 
    Infusion of cryopreserved stem cell products Nonimmune hemolysis may be observed during infusion of DMSO-cryopreserved HPC preparations DAT negative 
    Clostridium perfringens sepsis C perfringens produces hemolysin toxins, resulting in nonimmune intravascular hemolysis DAT negative 

DAT indicates direct antiglobulin test; C3D, complement factor 3D; DMSO, dimethyl sulfoxide; HPC, hematopoietic progenitor cell; IgG, immunoglobulin G; and RBC, red blood cell.

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