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Antenatal management in fetal and neonatal alloimmune thrombocytopenia: a systematic review

Dian Winkelhorst, Michael F. Murphy, Andreas Greinacher, Nadine Shehata, Taman Bakchoul, Edwin Massey, Jillian Baker, Lani Lieberman, Susano Tanael, Heather Hume, Donald M. Arnold, Shoma Baidya, Gerald Bertrand, James Bussel, Mette Kjaer, Cécile Kaplan, Jens Kjeldsen-Kragh, Dick Oepkes and Greg Ryan

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Tables

  • Table 1.

    Study outcomes

    ReferenceStudy arms (risk group in case of stratification)NICH in sibling, n (%)FBS, n (%)IUPT, n (%)FBS/IUPT-related AE, n (%)Duration IVIG, wk, mean (range)SE IVIG/ steroids, n (%)ICH, n (%)Mean PLTs × 109/LPLT < 50 × 109/L, n (%)Mortality, n (%)
    Randomized controlled trials
    30IVIG 0.5 g12000NA10 (7-11)00813 (25)0
    IVIG 1 g11000NA11 (7-12)001104 (36)0
    37IVIG 2 g370All02 (5)16 (11-20)12 (32)11695 (14)0
    IVIG 1 g + steroids360All02 (6)16 (12-19)13 (33)11344 (11)0
    35IVIG (all)404 (10)All011 (14)NRNR3104NR4 (5)
    IVIG + steroids (high)193 (16)All0NRNR99NR
    Steroids (standard)200All0NANR108NR
    20IVIG*286 (21)All05 (9)100096<30 6 (21)5 (9)
    IVIG + steroids264 (15)All0112 (8)0110<30 5 (19)
    Prospective studies
    17IVIG ± IUPT77 (100)3 (43)3 (43)NR17 (8-21)NR0287 (100)0
    39IUPT predelivery20All2 (100)NRNANA021000
    IVIG ± IUPT402 (50)2 (50)NR17 (15-19)NR020400
    IVIG + steroids132 (15)1 (8)1 (8)NR12 (5-20)NR01184 (31)0
    18IVIG ± IUPT378 (19)26 (70)26 (70)05 (2-15)NR06717 (46)0
    FBS ± IUPT13All9 (69)2 (22)NANA0327 (54)1 (8)
    23IVIG83 (30)AllNR2 (20)12 (3-16)NR0NR1 (13)0
    Fetal IVIG2AllNR2 (1-2)NR0NR2 (100)0
    22IVIG95 (56)All1 (11)NRNRNR0574 (44)NR
    IVIG + steroids93 (33)8 (89)0NRNR5 (56)0643 (33)NR
    Retrospective studies
    31IVIG 1 g (all)52 (40)00NANR01§638 (67)0
    IVIG 0.5 g (standard)17000NANR001044 (33)0
    32IVIG279 (14)00NA14NR08912 (44)0
    IVIG + steroids5400NA14NR013513 (27)0
    Steroids1100NANANR0468 (73)0
    24IVIG175 (29)901 (11)12NR06810 (59)0
    IVIG + steroids6000NA7NR0784 (67)0
    19IVIG 1 g (high + very high)55 (100)All1 (17)3 (8)15 (7-25)NR116500
    IVIG 1 g + steroids (all)1919 (100)All012 (5-25)NR3856 (40)2 (11)
    IVIG 2 g (all)44 (100)All022 (18-25)NR011200
    IVIG 2 g + steroids (all)99 (100)All023 (18-27)NR113500
    21Fetal IVIG + IUPT10NRAll10 (100)010 (6-14)NR018900
    26IVIG135 (38)NR2 (15)NRNRNR0836 (46)0
    34IVIG (all)535 (9)00NA8 (2-24)NR012510 (19)0
    FBS + IVIG (all)3311 (33)AllNR3 (7)6 (2-21)NR017401 (3)
    FBS + IUPT (standard)130All13 (100)0NANA01453 (23)0
    41IUPT ± IVIG ± steroids40NRAll40 (100)3 (8)NRNR4107NR6 (15)
    IVIG and/or steroids7NRNR01 (14)NRNR07-219NR1 (14)
    No treatment8NRNANANANANA06-84NR0
    38IVIG2404 (17)0NR15 (9-19)NR0118<30 2 (8)0
    No treatment60NANANANANA024<30 4 (67)0
    27IVIG*95 (56)00NANRNR0904 (44)0
    IUPT30All3 (100)3 (100)NANA0472 (100)1 (33)
    No treatment62 (34)00NANANA194 (80)1 (17)
    28IVIG ± IUPT*186 (60)All6 (33)3 (17)9 (1-19)1 (6)1§816 (33)0
    IUPT weekly3111 (42)All31 (100)10 (30)NANA2§NRNR3 (10)
    FBS ± single IUPT70All5 (71)2 (29)NANA0NRNR0
    42IVIG ± IUPT*111 (9)All9 (82)2 (18)6 (1-12)1 (9)01095 (45)0
    IUPT40All4 (100)2 (50)NANA0762 (50)0
    29IVIG277 (26)All1 (4)NR7 (2-15)NR26913 (48)2 (7)
    Steroids10NRAllNRNRNANRNRNR6 (60)NR
    33IVIG + IUPT41 (25)All4 (100)1 (25)NR0018201 (25)
    IVIG61 (17)All01 (17)NR00982 (33)1 (17)
    40IVIG + IUPT ± steroids86 (75)All6 (100)1 (13)9 (4-17)NR1§34002 (25)
    IUPT ± steroids75 (71)All7 (100)0NANR2§30501 (14)
    36IVIG2NRAll0NR14 (13-14)00601 (50)0
    IVIG + steroids4NRAll0NR11 (5-20)0014600
    25IUPT41 (20)All5 (100)0NANA020000
    IVIG (5 d) + IUPT10All1 (100)050010700
    • AE, adverse event; NA, not applicable; NR, not reported; SE, side effect.

    • * One or 2 patients also received steroids (supplemental Table 1).

    • Five fetuses exsanguinated and were excluded from other analyses.

    • Platelet count before predelivery IUPT.

    • § ICH occurred before start of therapy.

    • Platelet count after IUPT.

  • Table 2.
  • Table 3.

    Complications of antenatal treatment

    ReferenceAEs in FBS/IUPT n/N (%)*Complications after FBS or IUPT (n)SEs in IVIG n/N (%)*Reported SEs in IVIG treatment (n)SEs in steroids n/N (%)*Reported SEs in steroid treatment (n)
    241/9 (11)Emergency CS due to fetal distress (1); <34 wk (0)NRNRNRNR
    194/37 (11)Emergency CS or delivery (4); <34 wk (NR); due to fetal distress (3); insertion bleeding (1)NRNRNRNR
    343/99 (3)Perinatal death (1); emergency CS due to fetal distress (3); <34 wk (0)NRNRNANA
    374/74 (5)Emergency CS (4); <34 wk (3); due to fetal distress (2); PROM (2)NRRash (1) discontinued IVIG, headache, fatigueNRGestational diabetes (7), insomnia, mood swings
    3511/79 (14)Fetal death (1); neonatal death (1); emergency CS or delivery (10); <34 wk (NR); due to fetal distress (8); streaming (1); PROM (1)NRNRNRNR
    182/40 (5)Neonatal death after fetal distress (1); emergency CS due to exsanguination (1)NRNRNRNR
    2815/38 (39)Fetal death (2); after exsanguination (1); emergency CS/delivery (13); <34 wk (6); due to fetal distress (6), infection (1), technical difficulties (3), cord spasm or thrombosis (2), placental artery bleeding (1)1/18 (6)Headache and tachycardia (1), continued IVIGNRNR
    232/10 (20)Emergency CS due to insertion bleeding (2), <34 wk (1)NRNRNANA
    424/15 (27)Emergency CS or delivery (4); <34 wk (1); due to fetal distress (3); acute amnionitis after ROM (1)1/11 (9)Headache and tachycardia (1), continued IVIGNRNR
    205/59 (9)Fetal or neonatal death after exsanguination (5)0/54None2/26 (8)Oligohydramnios (2) dexamethasone 1.5 mg - dexamethasone 4.5 mg
    332/10 (20)Pregnancy loss at 16 wk’s gestation (1); neonatal death due to chorioamnionitis at 25 wk (1);0/10NoneNANA
    401/15 (7)fetal death due to cord hematoma (1)NRNRNRNR
    22NRNRNRNR5/9 (56)Oligohydramnios (4) dexamethasone 5 mg
    • AE, adverse event; CS, cesarean section; CTG, cardiotocogram; NR, not reported; PROM, prelabor rupture of membranes; SE, side effect.

    • * Number of reported complications (n) versus the total number of patients treated with this specific strategy (N).

    • Number of side effects reported; the total number of patients that reported a side effect is unclear.

    • The complications occurring during this study were reported in detail elsewhere.40