What condition results from immunization of the mother by fetal platelet antigen and placental transfer of maternal antibody, specifically Neonatal Alloimmune Thrombocytopenia (NAIT)?

Neonatal Alloimmune Thrombocytopenia (NAIT)

Neonatal alloimmune thrombocytopenia (NAIT) is the condition that results from immunization of the mother by fetal platelet antigens and placental transfer of maternal antibody. 1 This immune-mediated disorder occurs when maternal alloantibodies cross the placenta and target specific human platelet antigens (HPAs) present on fetal platelets but absent on maternal platelets.

Pathophysiology

NAIT develops through the following mechanism:

1. Maternal immunization: The mother lacks a specific platelet antigen that the fetus inherits from the father
2. Antibody production: The mother produces IgG alloantibodies against these "foreign" fetal platelet antigens
3. Placental transfer: These antibodies cross the placenta via active transport mediated by the neonatal Fc-receptor
4. Platelet destruction: The antibodies bind to fetal platelets, causing their destruction and resulting in thrombocytopenia

The International Society on Thrombosis and Haemostasis (ISTH) defines FNAIT as a platelet count below 100 × 10^9/L at birth or within 7 days after birth, or fetal intracranial hemorrhage, both in the absence of alternative causes 1.

Key Features

• Most commonly caused by antibodies against HPA-1a (approximately 85% of cases in Caucasian populations) 2
• Other platelet antigens can also be involved, including HPA-3, HPA-5, and HPA-15 1
• Platelet counts typically nadir between days 2-5 after birth, requiring ongoing monitoring 3
• The most feared complication is intracranial hemorrhage, which can lead to permanent neurological damage or death 4

Diagnosis

Laboratory confirmation of NAIT requires:

1. HPA genotyping of the mother, neonate (or father if neonatal sample unavailable)
2. Maternal alloantibody testing using specialized assays
3. Crossmatch with paternal platelets 1

Important diagnostic considerations:

• Delayed alloantibodies may appear several weeks after birth, requiring repeat testing 2-8 weeks later 1
• Low-affinity antibodies may cause false-negative results in some assays
• At least two different testing methods should be used to reduce the risk of false-negative results 1
• Other causes of neonatal thrombocytopenia (infection, hypoxia) should be excluded 1

Management

Antenatal Management (for subsequent pregnancies)

• IVIG is the cornerstone of treatment for pregnancies at risk of NAIT
• Standard dose: 1 g/kg/week for high-risk cases 3
• Cordocentesis carries a 1-2% fetal mortality risk and should be avoided 3

Delivery Planning

• Mode of delivery should be determined by obstetric indications, not NAIT status alone 3
• Avoid procedures with increased hemorrhagic risk during labor:
  • Fetal scalp electrodes
  • Fetal blood samples
  • Ventouse delivery
  • Rotational forceps 3

Neonatal Management

• Monitor platelet counts closely, even if initial counts are acceptable
• Platelet transfusions may be required for severe thrombocytopenia
• Avoid invasive procedures when possible

Differential Diagnosis

NAIT must be distinguished from other causes of neonatal thrombocytopenia:

• Maternal immune thrombocytopenia (ITP)
• Infection
• Hypoxia
• Disseminated intravascular coagulation
• Congenital thrombocytopenia syndromes

Conclusion

NAIT is a serious condition that requires prompt diagnosis and management to prevent severe bleeding complications, particularly intracranial hemorrhage. Laboratory confirmation involves specialized testing to identify platelet antigen incompatibility and maternal alloantibodies. Management focuses on preventing bleeding complications and planning appropriate care for subsequent pregnancies.