Advertisement

High prevalence of red blood cell alloimmunization in sickle cell disease despite transfusion from Rh-matched minority donors

Stella T. Chou, Tannoa Jackson, Sunitha Vege, Kim Smith-Whitley, David F. Friedman and Connie M. Westhoff

Data supplements

Article Figures & Data

Figures

  • Figure 1

    RBC immunization in patients with SCD transfused with Rh D, C, and E and K matched RBCs from minority donors. (A) One hundred forty-six specific antibodies in 123 chronically and 59 episodically transfused patients. (B) Number of antibodies per patient. (C) Number of Rh antibodies per patient. (D) Number of patients with anti-D, -C, -E, or -e in their serum and whose RBCs type positive or negative for the antigen.

  • Figure 2

    DTRs in patients with unexplained Rh antibodies. Percent hemoglobin S and hemoglobin levels in 3 representative cases of chronically transfused patients with anti-D, -C, and -e (see Table 2 for values of all DTRs associated with Rh antibodies). Each point represents a pretransfusion value coinciding with transfusions occurring at 3-week intervals. Arrows indicate time of antibody detection. The dotted line represents the mean percent hemoglobin S or hemoglobin level for that individual determined pretransfusion for 9 visits preceding antibody detection. The SD for means was calculated. The difference between the baseline and the value at time of antibody formation is expressed as a multiple of this SD, or Z-score. The gray shaded area indicates values that would have a Z-score <2. Z-score >2.0 for hemoglobin S level or <−2.0 for hemoglobin level correlates with P < .05. The double lines on the top charts indicate a several-month period when transfusions were discontinued.

  • Figure 3

    RHD and RHCE diversity in 226 patients with SCD. RH alleles identified in patients with SCD. Each gray box represents 1 of 10 exons in the RH genes. Black boxes represent exon exchange between RHD and RHCE. Vertical black lines indicate position in the exon encoding amino acid substitutions in the protein. Dashed lines indicate gene deletion. Arrowhead indicates 37-bp duplication. Hatched boxes represent exons encoding a frameshift and untranslated region of the inactive RHD pseudogene.

Tables

  • Table 1

    Transfused patient characteristics

    Episodic categoryChronic category
    Overall demographicsEpisodic categoryChronic categoryAlloimmunizedNonalloimmunizedP valueAlloimmunizedNonalloimmunizedP value
    No. of patients182
    Male/female112/70 (61.5% male)
    Median age (years)15.7 (range 0.5-41)
    Transfusion category
     No. of patients (%)59 (32.4)123 (67.6)
     Donor RBC exposures (units)
      Mean4.6354
      Median3230
      Range1-1510-1460
      Total for group27244 210
    Alloimmunization status
     No. of patients (%)9 (15.2)50 (84.8)NA71 (57.7)52 (42.3)NA
     No. of male patients (%)3 (33.3)28 (56.0).31748 (67.6)30 (57.7).003
     Mean age (years)14.511.6.20019.115.7.007
     Mean age at first transfusion (years)3.95.3.3276.56.8.755
     Donor RBC exposures (units)
      Mean8.93.8<.001408.6292.3.045
      Median92.5<.001309192.5.008
      Range3-151-12NA12-126310-1460NA
      Total for group80192NA29 00915 201NA
    • NA, not applicable; bold indicates statistically significant (P < .05).

  • Table 2

    Twenty-nine Rh antibodies in 25 patients associated with a significant change in hematologic parameters

    Antibody specificityConcurrent AntibodiesIDHemoglobin S (%)Hemoglobin (g/dL)
    BaselineAt antibody detectionZ-score*BaselineAt antibody detectionZ-score*
    Patients whose RBCs type positive for the corresponding antigen
     D (n = 12)29281.76.54.25.7
    E9527.168.010.49.17.53.2
    4125.938.25.99.48.92.4
    7828.845.15.410.29.7−0.5
    C13819.361.64.310.48.24.0
    C7728.845.33.58.08.10.2
    11027.610.67.92.7
    5044.358.81.68.56.42.8
    9929.645.72.58.98.2−1.0
    3418.223.32.28.88.7−0.2
    14526.032.72.19.59.5−0.1
    10024.840.62.08.97.5−1.8
     C (n = 3)9525.331.21.09.35.06.9
    D13819.361.64.310.48.24.0
    8528.944.02.79.88.82.3
     e (n = 5)6529.043.64.98.78.2−0.7
    10823.150.74.47.66.34.1
    C9776.39.06.37.6
    10026.440.62.18.68.12.7
    8689.57.76.92.1
    Patients whose RBCs type negative for the corresponding antigen and received antigen negative RBCs
     C (n = 4)2825.145.88.09.48.7−1.3
    D7728.845.33.58.08.10.2
    e9776.39.06.37.6
    13037.534.9−0.88.98.25.0
     E (n = 4)D9527.168.010.49.17.53.2
    10324.366.18.910.07.66.9
    159509.25.16.8
    Jkb3143.191.52.07.96.8−1.1
    Patients whose RBCs type negative for the corresponding antigen and received antigen positive RBCs
     E (n = 1)6332.350.74.49.58.92.1
    • For each antibody, the percent hemoglobin S and hemoglobin level at the time of first detection is indicated and compared with the patient’s individual baseline value (see Methods). For antibody specificity, the second entry indicates additional antibodies detected concurrently. —, data not available.

    • * Z-score >2.0 for hemoglobin S level or <−2.0 for hemoglobin level correlates with P < .05, indicated in bold. ID in bold indicates patients with >1 Rh antibody detected concurrently.

    • Episodically transfused.

    • E− transfused with E+ RBCs for management of anti-e.

  • Table 3

    RHD genotype and production of anti-D: clinical significance, donor exposures, and antibody duration

    Antibody specificityConcurrent AntibodiesIDRH genotypeDTRRBC exposuresAntibody demon-stration (months)
    RHDRHCE
    D+ patients lacking conventional RHD
     D (n = 7)292*DAU4DAU4ce(48C)ce(48C)Yes2
    50DAU0DAU5ce(48C)ce(48C)Yes911
    34DAU0Deleted Dce(733G)ceYes2693
    E104DAU3DAU5ce(48C)cENo3919
    C214*DAU0Weak partial 4.0ce(48C)ce(48C,733G)SS4
    117Weak partial 4.0Weak partial 4.0ce(254G)ce(48C,733G)No322
    14DIVa-2DIIIa-CE(4-7)-DceceSNo1811
    D+ patients with one or more conventional RHD
     D (n = 22)100RHDDIIIa-CE(4-7)-Dce(733G)ceSYes9814
    141*RHDDIIIa-CE(4-7)-Dce(733G)ceSNo536
    S44RHDDIIIa-CE(4-7)-DceceSNo1161
    94RHDDIIIa-CE(4-7)-DceceSNo8216
    C138RHDDIIIa-CE(4-7)-DCeceSYes1035+
    110RHDWeak partial 4.0CeceSYes283
    72RHDDIVa-2ceTIceTINo1111
    E28RHDDAU0ceHARce(48C)No2121
    30RHDDAU0Cece(48C)No1771
    99RHDDeleted DCecEYes287
    17RHDDeleted DcEceNo3311
    95RHDDeleted DCeceTINo1554
    E95RHDDeleted DCeceTIYes3691
    21RHDDeleted DCece(733G)No4261
    78RHDDeleted Dce(733G)ce(254G)Yes1991
    19RHDRHDceceNo7331
    18RHDRHDcEceNo6454
    41RHDRHDcece(733G)Yes4296
    145RHDRHDCece(733G)Yes481
    C20RHDRHDcece(733G)No2241
    69RHDRHDce(733G)ce(733G)No2301
    C77RHDRHDcece(254G)Yes125
    103RHDRHDce(48C)ceS
    D− patient
     D10Deleted DInactive RHD ψce(254G)ce(48C)No314112+
    • DTR, DTR from Table 2; RBC exposures, cumulative number of RBC units transfused prior to antibody detection; antibody demonstration, number of months anti-D was detected. Additional antibody detected concurrently is indicated in the second column. SS, confounded by splenic sequestration; —, data not available; +, remains detectable; italicized patient demonstrates anti-D recurrence.

    • * Episodically transfused.

  • Table 4

    RHCE genotype and production of anti-C, -e, or -E: clinical significance, donor exposures, and antibody duration

    Antibody specificityConcurrent AntibodiesIDRH genotypeDTRRBC exposuresAntibody demon-stration (months)
    RHCERHD
    C+ patients lacking conventional RHCE*Ce
     C (n = 5)100ceSce(733G)DIIIa-CE(4-7)-DRHDNo5239
    94ceSceDIIIa-CE(4-7)-DRHDNo1154
    105*ceScEDIIIa-CE(4-7)-DRHDNo12
    85ceSceTIDIIIa-CE(4-7)-DDIVa-2Yes6513
    118ceSceTIDIIIa-CE(4-7)-DDIVa-3
    C+ patients with one conventional RHCE*Ce
     C (n = 4)D138CeceSRHDDIIIa-CE(4-7)-DYes1031
    95CeceTIRHDDeleted DYes3652
    96Cece(733G)RHDDeleted DNo8232
    21Cece(733G)RHDDeleted D
    e+ patients lacking conventional RHCE*ce
     e (n = 14)C97*ce(48C)ce(48C)RHDRHDYes1
    75ce(48C)ce(48C)DAU0DAU5No911
    108ce(48C)ce(733G)DAU0Inactive RHD ψYes1071
    102ce(48C)ce(733G)DAU0RHDNo29524
    148ce(48C)ce(733G)Weak partial 4.0Weak partial 4.0No64
    65ce(48C)ceSDAU3DIIIaYes17419
    63ce(48C)ceSDAU0DIIIa-CE(4-7)-DNo1951
    100ce(733G)ceSRHDDIIIa-CE(4-7)-DYes6236
    96ce(733G)CeDeleted DRHDNo6410
    93ce(733G)CeRHDRHDNo241
    45ce(733G)cERHDRHD
    86ce(48C,733G)cEWeak partial 4.0RHDYes81
    C98ce(254G)cERHDDeleted DNo9211
    C60ce(254G)cEDAU0RHDNo4022
    e+ patients with one conventional RHCE*ce
     e (n = 2)27cece(48C)RHDDAU0No39649
    94ceceSRHDDIIIa-CE(4-7)-DNo2812
    E+ patients with one conventional RHCE*cE
     E (n = 2)17cEceRHDDeleted D2791
    D104cEce(48C)DAU3DAU5No3919
    • DTR, DTR from Table 2; RBC exposures, cumulative number of units transfused prior to antibody detection; antibody demonstration, the number of months antibody was detected. Additional antibody detected concurrently is indicated in the second column. —, data not available.

    • * Episodically transfused patient.