Fetal and neonatal alloimmune thrombocytopenia: a late or missed diagnosis disease in fetal and perinatal health-care settings

Abstract

Introduction

Even though Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT) has been recognized as the main cause of primary hemorrhagic morbidity and mortality in fetuses and newborns, screening programs to detect pregnancies at risk have not yet been implemented in any country. Moreover, in spite of increased concerns about maternal, fetal and neonatal health care in general, this potentially lethal disease is still underdiagnosed. The aim of this report is to highlight the importance of considering FNAIT in fetal and perinatal health-care settings and show the usefulness of molecular tools in early diagnosis of this clinical entity.

Methods

DNA was extracted from whole blood from parents and newborns; genotyping was performed by in house PCR using sequence-specific primers for typing Human Platelet Antigens (HPA)-1 to -6, -9, and -15, and with commercial HPA-TYPE (BAG HealthCare, Lich, Germany). Anti-HPA antibodies in the maternal serum were detected by the Monoclonal Antibody Solid Phase Platelet antibody Test (MASPAT). Chloroquine-treated platelets were used for the discrimination of platelet-specific antibodies from anti-HLA antibodies.

Results

Patients 1 and 2 had severe thrombocytopenia due to incompatibility in HPA-1 and HPA-15, respectively. The third case was a thrombocytopenic neonate with severe bleeding complications other than ICH and in whom differential diagnosis between FNAIT and Von Willebrand congenital disease was necessary; incompatibility in HPA-15 was also demonstrated. Case 4 represents a missed diagnostic opportunity.

Conclusion

This is the first report of FNAIT cases confirmed by molecular evidence and anti-HPA antibodies detection in Argentina. This report reinforces the relevance of early diagnosis of this clinical entity. Since the delay in FNAIT diagnosis could lead to severe consequences in the fetus and neonates, strategies to approach maternal, fetal, and perinatal health, as well as prevention policies aimed to reduce fetal and neonatal morbidity and mortality should focus on implementing programs to identify high-risk pregnancies and thus reduce thrombocytopenia-related complications in fetuses and newborns.

Keywords:

• Antenatal screening
• delayed diagnosis
• extracranial hemorrhage
• human platelet antigens
• neonatal alloimmune thrombocytopenia

Author contributions

SB and SVG conceived and designed the study. LCV, LHC, and JMC recruited and followed the patients. SB and SVG processed the samples. All the authors analyzed the data. SB and SVG drafted the manuscript. SB, LCV, LHC, JMC, and SVG revised and edited the final version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

Funds were provided by Fundación Banco Central de Sangre and Facultad de Ciencias Médicas, Universidad Nacional de Córdoba.