Neonatal Alloimmune Thrombocytopenia - NAIT

Neonatal alloimmune thrombocytopenia (NAIT), also referred to as perinatal alloimmune thrombocytopenia (PAT) or 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 may lead to devastating consequences, including intracranial hemorrhage (ICH) and death.

  • Diagnosis
  • Screening
  • Monitoring
  • Background
  • Lab Tests
  • References
  • Related Topics

Indications for Testing

  • Fetal or neonatal testing
    • Parents have had a prior affected pregnancy
    • Unexplained intracranial hemorrhage detected
    • Unexplained thrombocytopenia detected
  • Maternal and paternal testing – 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 posttransfusion purpura

Laboratory Testing

  • CBC with platelet count – testing for infant
    • NAIT does not cause thrombocytopenia in the mother 
    • Platelet count is often <50,000/μL
  • Testing and test interpretation in suspected NAIT should be performed by an experienced platelet immunology reference laboratory
    • Combination of test results used to determine likelihood of NAIT
    • Antiplatelet antibody
      • Maternal sample preferred
      • Tests detect maternal antibodies to antigens commonly implicated in NAIT
        • Human platelet antigens (HPA) 1, 3, and 5 should be screened in all suspected cases
          • Include HPA 4 if 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

Imaging Studies

Computed tomography (CT)/magnetic resonance imaging (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
      • Congenital heart disease
    • Miscellaneous
  • Decreased platelet production
    • Infiltrative disorders
    • Hereditary thrombocytopenia
      • Thrombocytopenia with absent radius (TAR) syndrome
      • Wiskott-Aldrich syndrome
      • MYH9 macrothrombocytopenia syndromes
        • May-Hegglin anomaly
        • Sebastian syndrome
        • Fechtner syndrome
      • Amegakaryocytic thrombocytopenia
      • Fanconi anemia
    • 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, 2010).

  • Routine monitoring for intracranial hemorrhage (ICH) not recommended in pregnant population
  • Monitoring recommended in mother with previous infant with neonatal alloimmune thrombocytopenia (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) may be warranted


  • Incidence – 1/2,000 pregnancies (Smock, 2014)
  • Age
    • Affects fetus or neonate only
    • Occurs as early as 18-20 weeks gestation
  • Sex – M:F, equal for infants


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


  • HPA 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
    • 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
    • Sometimes termed the platelet equivalent of Rh disease
    • At-risk women may be identified after having an affected pregnancy
      • 40-60% present in first pregnancy (unlike Rh alloimmunization)
  • Most commonly occurs in women lacking HPA-1a
    • 80-90% of cases occur in HPA-1a negative mothers
      • 2-5% of Caucasians lack HPA-1a 
    • HPA-1a and HPA-5b are the most commonly involved HPAs
    • HPA-1a incompatibility causes most severe form of the disease
      • HPA-3a causes next most severe form

Clinical Presentation

  • Otherwise healthy newborn with severe thrombocytopenia (<50,000/µL)
  • Widespread petechiae or purpura
  • Visceral hemorrhage – often gastrointestinal or bladder mucosa
  • ICH – may occur in utero, at birth, or antenatally
    • Risk is related to absolute platelet count
    • Fatal in 5-10% of affected neonates
    • Intellectual disability, seizures, cerebral palsy, or cortical blindness in up to 25% of survivors
  • Recurrence rate up to 90% in subsequent pregnancies – severity may increase with subsequent pregnancies
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.

CBC with Platelet Count 0040002
Method: Automated Cell Count

Platelet Antibodies, Indirect 0051050
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Platelet Antigen Genotyping Panel 0051308
Method: Polymerase Chain Reaction/Fluorescence Monitoring


HPA genes and variants other than those tested are not determined

Bloody amniotic fluid specimens may give false-negative results due to maternal cell contamination

Diagnostic errors can occur due to rare sequence variations

General References

Curtis BR. Genotyping for human platelet alloantigen polymorphisms: applications in the diagnosis of alloimmune platelet disorders. Semin Thromb Hemost. 2008; 34(6): 539-48. PubMed

Gunnink SF, Vlug R, Fijnvandraat K, van der Bom JG, Stanworth SJ, Lopriore E. Neonatal thrombocytopenia: etiology, management and outcome. Expert Rev Hematol. 2014; 7(3): 387-95. PubMed

Heikal NM, Smock KJ. Laboratory testing for platelet antibodies. Am J Hematol. 2013; 88(9): 818-21. PubMed

Kamphuis MM, Paridaans N, Porcelijn L, De Haas M, Van Der Schoot CE, Brand A, Bonsel GJ, Oepkes D. Screening in pregnancy for fetal or neonatal alloimmune thrombocytopenia: systematic review. BJOG. 2010; 117(11): 1335-43. PubMed

Kjeldsen-Kragh J, Killie MK, Tomter G, Golebiowska E, Randen I, Hauge R, Aune B, Oian P, Dahl LB, Pirhonen J, Lindeman R, Husby H, Haugen G, Grønn M, Skogen B, Husebekk A. A screening and intervention program aimed to reduce mortality and serious morbidity associated with severe neonatal alloimmune thrombocytopenia. Blood. 2007; 110(3): 833-9. PubMed

Peterson JA, McFarland JG, Curtis BR, Aster RH. Neonatal alloimmune thrombocytopenia: pathogenesis, diagnosis and management. Br J Haematol. 2013; 161(1): 3-14. PubMed

Sachs UJ. Fetal/neonatal alloimmune thrombocytopenia. Thromb Res. 2013; 131 Suppl 1: S42-6. PubMed

Skogen B, Killie MK, Kjeldsen-Kragh J, Ahlen MT, Tiller H, Stuge TB, Husebekk A. Reconsidering fetal and neonatal alloimmune thrombocytopenia with a focus on screening and prevention. Expert Rev Hematol. 2010; 3(5): 559-66. PubMed

Smock KJ, Perkins SL. Thrombocytopenia: an update. Int J Lab Hematol. 2014; 36(3): 269-78. PubMed

Strong NK, Eddleman KA. Diagnosis and management of neonatal alloimmune thrombocytopenia in pregnancy. Clin Lab Med. 2013; 33(2): 311-25. PubMed

Symington A, Paes B. Fetal and neonatal alloimmune thrombocytopenia: harvesting the evidence to develop a clinical approach to management. Am J Perinatol. 2011; 28(2): 137-44. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Heikal NM, Smock KJ. Laboratory testing for platelet antibodies. Am J Hematol. 2013; 88(9): 818-21. PubMed

Medical Reviewers

Last Update: October 2017