Neonatal Alloimmune Thrombocytopenia - NAIT


Indications for Testing

  • Fetal or neonatal testing when
    • Parents have had a prior affected pregnancy
    • Unexplained intracranial hemorrhage is detected
  • Maternal and paternal testing when
    • Fetus or neonate is suspected to have neonatal alloimmune thrombocytopenia (NAIT) (also referred to as perinatal alloimmune thrombocytopenia [PAT])
  • Female patients
    • Planning a pregnancy who have a sister with a previously affected pregnancy
    • With post-transfusion purpura

Laboratory Testing

  • CBC with platelet count – testing on infant
    • NAIT does not cause thrombocytopenia in the mother 
    • Platelet count is often <50,000/μL (variable)
  • Testing and test interpretation in suspected NAIT should be performed by an experienced platelet immunology reference laboratory
    • A combination of test results are used to determine the likelihood of NAIT
    • Anti-platelet antibody – maternal sample preferred
      • Tests detect maternal antibodies to antigens commonly implicated in NAIT
        • HPA 1, 3, and 5 should be screened in all suspected cases
          • Include HPA 4 if the patient is of Asian descent
        • Identification of a maternal antibody is not diagnostic of NAIT – additional testing needed
        • Tests vary in the antibodies that can be detected
        • Antibodies directed against rare platelet antigens are not detected by most tests
        • Absence of a detectable maternal antibody does not exclude a diagnosis of NAIT
    • Platelet phenotyping or platelet antigen genotyping of mother and father
      • Detect maternal/paternal incompatibilities between HPA antigens
      • Genotyping allows for more accurate risk assessment and better pregnancy management
      • Fetal or neonatal platelet typing is not usually performed
      • For reference laboratories performing followup testing for NAIT, refer to the following

Imaging Studies

  • CT/MRI – mandatory for thrombocytopenic neonate

Differential Diagnosis of Thrombocytopenia in a Newborn (Strong, 2013)

  • Increased platelet consumption
    • Immune-mediated
      • Autoimmune (including maternal idiopathic thrombocytopenic purpura)
      • Alloimmune
      • Drug-induced
    • Peripheral consumption
      • Hypersplenism
      • Kasabach-Merritt syndrome (giant hemangioma)
      • Disseminated intravascular coagulation
      • Necrotizing enterocolitis
    • Miscellaneous
  • Decreased platelet production
    • Infiltrative disorders
    • TAR syndrome
    • Wiskott-Aldrich syndrome
    • Congenital leukemia
    • Osteopetrosis
  • Mixed causes


  • Generalized screening is not recommended; however, several prospective studies involving >100,000 pregnancies suggest there may be a role for screening and intervention (Skogen, et al, 2010)


  • Routine monitoring for intracranial hemorrhage (ICH) not recommended in general population
  • Monitoring recommended in mother with previous infant with NAIT or ICH
    • Fetal blood sampling may be performed but is not recommended due to bleeding
    • Institution of intravenous immunoglobulin early in pregnancy (as early as 12 weeks, depending on when gestational date ICH was noted in previous neonate)

Clinical Background

Neonatal alloimmune thrombocytopenia (NAIT), also referred to as fetal and neonatal alloimmune thrombocytopenia, is the most common cause of severe thrombocytopenia (platelet count <50,000/µL) in the first few days of life of an otherwise healthy newborn. NAIT also may be referred to as perinatal alloimmune thrombocytopenia or PAT. This disease may lead to devastating consequences, including intracranial hemorrhage and death.


  • Incidence – 1/1,000-1/5,000 births
    • Transfusion purpura is less frequent
  • Age – affects fetus or neonate only; can occur as early as 18-20 weeks gestation
  • Sex – M:F, equal


  • ~16 different types of human platelet antigens (HPA) have been identified
  • More common allele is designated “a” and the less common is “b”
  • HPA-1a is believed to cause ~80% of PAT; HPA-5b causes 20% in Caucasians
  • HPA-1a-positive individuals have at least one copy of the “a” allele; HPA-1a-negative individuals are homozygous for the HPA-1b allele
    • 2% of women are homozygous for HPA-1b
      • These women are at risk for alloimmunization during pregnancy if their partner is homozygous HPA-1a or heterozygous HPA1- a/b and contributes the HPA-1a allele to the fetus

Risk Factors

  • Previous child with NAIT or family history of NAIT
    • 50% of cases occur during a first pregnancy


  • Human platelet antigens (HPA) are found on surface of platelet

    • Portion of population lacks this antigen
    • 24 platelet alloantigens, but only a small number are responsible for most NAIT
  • Maternal alloimmunization against fetal platelet antigens inherited from the father
    • Sometimes termed the platelet equivalent of Rh disease
    • At-risk women may be identified after having an affected pregnancy
      • 40-60% may present in first pregnancy (unlike Rh alloimmunization)
  • Most commonly occurs in women lacking HPA-1a
    • 2-5% of Caucasians lack HPA-1a
    • 80-90% of cases occur in HPA-1a negative mothers
      • 98% of the U.S. population is HPA-1a positive
    • HPA-1a incompatibility causes the most severe form of the disease; HPA-3a causes the next most severe form
    • HPA-1a and HPA-5b are the most commonly involved HPAs
  • Maternal IgG antibodies against fetal HPA can cross the placenta, causing fetal platelet destruction
  • Clinical correlation between antibody titers and NAIT occurrence is not reliable

Clinical Presentation

  • Otherwise healthy newborn with severe thrombocytopenia (<50,000/µL)
  • Widespread petechiae or purpura
  • Visceral hemorrhage – often gastrointestinal or bladder mucosa
  • Intracranial hemorrhage – may occur in utero, at birth, or antenatally
    • Risk is related to absolute platelet count
    • Fatal in as many as one-third of patients
    • Neurologic impairment in 20-30% of patients
  • Recurrence rate up to 90% in subsequent pregnancies
    • Severity may worsen with subsequent pregnancies


  • Fetal platelet transfusion with random platelets or antigen-negative platelets
  • Intravenous gammaglobulin or steroids

Indications for Laboratory Testing

  • Tests generally appear in the order most useful for common clinical situations
  • Click on number for test-specific information in the ARUP Laboratory Test Directory
Test Name and Number Recommended Use Limitations Follow Up
CBC with Platelet Count 0040002
Method: Automated Cell Count

Detect thrombocytopenia in neonate

Test neonate sample only; NAIT does not affect the mother

Platelet Antibodies, Indirect with Reflex to Identification 0051718
Method: Enzyme-Linked Immunosorbent Assay

Preferred test for platelet-specific antibodies in suspected neonatal alloimmune thrombocytopenia, posttransfusion purpura, or multiplatelet transfusion refractoriness

Glycoproteins include

  • GPIIb/IIIa complex including HPA-1a (PlA1), HPA-1b (PlA2), HPA-3a (Baka), HPA-3b (Bakb), and HPA-4a (Pena)
  • GPIa/IIa complex (HPA-5a and HPA-5b) and antibodies against GPIb/IX and GPIV

Reflex pattern – if platelet antibodies directed toward GP IIb/IIIa are present, additional testing identifies the specific GP IIb/IIIa epitope

  • HPA-1a/1b
  • HPA-3a/3b
  • HPA-4a

Recommend testing on maternal sample as unbound platelet antibodies may not be detected in neonatal serum

Detection of a platelet antibody is not diagnostic for NAIT

Antibodies to HPA-4b (Penb) may not be detected

Antibodies to platelet antigens not listed will not be detected

Detects both alloantibodies and autoantibodies but will not distinguish between them

Confirmatory testing for NAIT should be conducted by a platelet immunology reference laboratory such as Puget Sound Blood Center or Blood Center of Wisconsin
Platelet Antigen Genotyping Panel 0051308
Method: Polymerase Chain Reaction/Fluorescence Monitoring

Assess risk for NAIT; may be ordered for parental, fetal/neonatal testing

Clinical sensitivity/specificity – unknown

Antigens tested include a and b variants of HPA-1 through -6 and HPA-15

Tests may be ordered individually or as a panel; test performed with whole blood, amniotic fluid, or cultured amniocytes

HPA alleles other than those tested are not determined

Bloody amniotic fluid specimens may give false-negative results because of maternal cell contamination

Diagnostic errors can occur due to rare sequence variations

Additional Tests Available
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Platelet Antibodies, Indirect 0051050
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Use to detect platelet-specific antibodies in suspected neonatal alloimmune thrombocytopenia, posttransfusion purpura, or multiplatelet transfusion refractoriness

Not recommended for the diagnosis of immune thrombocytopenic purpura; preferred test is Platelet Antibodies, Indirect with Reflex to Identification

Platelet Antigen 1 Genotyping (HPA-1) 0051309
Method: Polymerase Chain Reaction/Fluorescence Monitoring
Platelet Antigen 2 Genotyping (HPA-2) 0051310
Method: Polymerase Chain Reaction/Fluorescence Monitoring
Platelet Antigen 3 Genotyping (HPA-3) 0051311
Method: Polymerase Chain Reaction/Fluorescence Monitoring
Platelet Antigen 4 Genotyping (HPA-4) 0051490
Method: Polymerase Chain Reaction/Fluorescence Monitoring
Platelet Antigen 5 Genotyping (HPA-5) 0051312
Method: Polymerase Chain Reaction/Fluorescence Monitoring
Platelet Antigen 6 Genotyping (HPA-6) 0051313
Method: Polymerase Chain Reaction/Fluorescence Monitoring
Platelet Antigen 15 Genotyping (HPA-15) 0051314
Method: Polymerase Chain Reaction/Fluorescence Monitoring
Platelet Antibody (Glycoprotein) Plasma/Eluate 2007237
Method: Qualitative Enzyme-Linked Immunosorbent Assay