Fetal and neonatal alloimmune thrombocytopenia: predictive factors of intracranial hemorrhage

Abstract

BACKGROUND In Caucasians, fetal/neonatal alloimmune thrombocytopenia (FNAIT) is most frequently caused by maternal alloimmunization against the human platelet antigen HPA‐1a. The most serious complication of severe FNAIT is intracranial hemorrhage (ICH). ICH mainly occurs in utero; therefore, there is a need to identify noninvasive predictive factors of ICH to facilitate early identification of this condition and to determine response to maternal therapy. STUDY DESIGN AND METHODS We studied gynecologic and immunogenetic variables of severe cases of anti‐HPA‐1a FNAIT within three groups: Group I, FNAIT without ICH; Group II, FNAIT with ICH; and Group III, suspected FNAIT cases without detectable maternal anti‐HPA‐1a alloantibodies. RESULTS ICH was associated with a poor outcome because it led to death in 59% of cases. Multigravida (two or more pregnancies) was overrepresented in Group II, consistent with the high concentrations of maternal HPA‐1a alloantibody and the frequent detection of a strong newborn‐specific HLA class I antibody response at delivery. The proportion of HLA‐DRB4*01:01P (*01:01 or *01:03) women was similar in Groups I and II, but this allele was overrepresented in Group III, in which FNAIT was less severe than in the other two groups. Finally, antenatal intravenous immunoglobulin therapy tended to be more effective in HLA‐DRB3*01:01(+)/HLA‐DRB4*01:01P(+) women than for HLA‐DRB3*01:01(+)/HLA‐DRB4*01:01P(–) women. CONCLUSION The number of gestations is a predictive factor of ICH in anti‐HPA‐1a–alloimmunized women. Maternal immunogenetic variables should be investigated in the context of maternal immunization and may predict response to maternal therapy in subsequent pregnancies.

Maternal HLA genotyping is not useful for predicting severity of fetal and neonatal alloimmune thrombocytopenia

“…In the aforementioned Israeli study, Loewenthal et al (2013) suggested that compound heterozygosity for DRB4*01:01 and DRB3*01:01 reduces the success of IVIG treatment based on their finding that only 17% of the infants born to women carrying both alleles achieved platelet counts of over 100 9 10 9 /l, in comparison to 67% of the newborns carrying only DRB3*01:01. Our results, with the corresponding rates of 50% and 8%, respectively, were more in line with a very recent French study (Delbos et al, 2016), but similarly, none of the figures were statistically significant. Finally, although the haplotype HLA-A*01:01-C*07:01-B*08:01-DRB3*01:01-DRB1*03:01-DQA1*05:01-DQB1*02:01 was overrepresented in the confirmed cases, six other haplotypes were also detected in our cohort.…”

“…Only a few studies report an association between the HLA-DRB3*01:01 type and quantitation of the anti-HPA-1a levels (Killie et al, 2008;Bertrand et al, 2011). Recent studies on other allele variants of the HLA-DR family involved in the severity of FNAIT and the responsiveness to IVIG treatment show conflicting results (Loewenthal et al, 2013;Delbos et al, 2016).…”

Current perspectives on fetal and neonatal alloimmune thrombocytopenia – increasing clinical concerns and new treatment opportunities

“…The clinical outcome of ICH due to FNAIT is reported to be worse compared to neonatal ICH from other causes75,76 and may be connected to the typical locations of the bleedings in the brain. Severe neurological complications are found in 36%–68% of ICH cases24,26,77,78 and fetal or neonatal death due to ICH is reported in the range of 9%–46%24,57,68,79 when evaluated retrospectively. A large cohort study from the international No Intracranial Hemorrhage (NOICH) registry described 43 cases of ICH caused by FNAIT in depth and found that the majority of bleedings (54%) happened before the third trimester and 67% before 34 gestational weeks 77.…”

Association between Fetal Cerebral Ventriculomegaly and Platelet Alloimmunisation

“…In the past literature, the mortality rate of ICH was up to 10% [17] and even more in recent studies [19,25] . ICH has been documented as early as 20 weeks of gestation, and 80% of ICH cases occur before the 30th week [18,19,26] .…”

“…A serious consequence of FNAIT is intracerebral haemorrhage (ICH), which has been reported to occur in 20-25% of cases [8,16,17] and may lead to neurological impairment and death [18][19][20][21][22][23][24] . In the past literature, the mortality rate of ICH was up to 10% [17] and even more in recent studies [19,25] . ICH has been documented as early as 20 weeks of gestation, and 80% of ICH cases occur before the 30th week [18,19,26] .…”