Neonatal Alloimmune Thrombocytopenia
(NAIT)

Reviewed by Alan Groves and Carl Kuschel

April
2003

Background	Presentation	Differential Diagnosis	Investigation
Management	References		Index of Related Documents

Low platelet count in an otherwise healthy term newborn is due to NAIT until proven otherwise.
Urgent matched platelet transfusion should be discussed with specialist on call at all times.

Background

Neonatal Alloimmune Thrombocytopenia (NAIT) is a disorder caused by fetomaternal platelet incompatibility analogous to that in Rhesus Haemolytic Disease, with maternal anti-platelet antibodies crossing the placenta and destroying fetal platelets.
The majority of cases are caused by antibodies directed against Human Platelet Antigen-1a (HPA-1a) and HPA-5b, but many rarer reactions have been reported.
Prospective studies have shown incidence to be 1:1,100 live births,¹ but the condition is under-reported.²
Mortality is around 10% of presenting cases, with neurological sequelae, including intracranial haemorrhage and subsequent neurodevelopmental delay in up to 25%.³

Presentation

The commonest mode of presentation is probably the well neonate with bruises or petechiae. However the spectrum of disease ranges from sub-clinical moderate thrombocytopenia to catastrophic intracranial hemorrhage (ICH) and death. A high index of suspicion is essential in all cases of active bleeding, but also in asymptomatic laboratory diagnosed thrombocytopenia. A history of thrombocytopenia in a previous sibling makes the diagnosis almost certain.

Modes of presentation

Previously affected sibling
Recurrent fetal loss
Antenatal ICH/hydrocephalus
Stillbirth
Bruising/bleeding neonate
Excessive haematoma at injection site
Disseminated intravascular coagulopathy
Postnatal ICH (silent or presenting with seizures, etc)

Differential Diagnosis

Also see Neonatal Thrombocytopenia protocol

Sepsis
NEC
DIC
Placental insufficiency
Congenital infection
Asphyxia
Artefact - clotted FBC sample
Autoimmune thrombocytopenia (maternal ITP)

Investigation

FBC	to confirm platelet count
Maternal FBC	likely to have been performed during pregnancy. Maternal platelet count is normal in NAIT.
Definitive diagnosis of NAIT depends on parental testing. In most cases the lab prefers to do this prior to platelet transfusion, but discussion with haematologist on call is necessary to arrange urgent testing. FURTHER TESTING SHOULD NOT DELAY PLATELET TRANSFUSION IF REQUIRED URGENTLY
Maternal blood samples	3 x CPD (yellow) and 1x plain (red) tubes for anti-platelet antibodies and genotyping.
Paternal blood samples	3 x CPD (yellow) tubes for genotyping. If no paternal blood available, send 1 x CPD (yellow) tube for platelet grouping.

Direct crossmatch between parents will also be performed.
Maternal antibody levels fall towards term, so repeat testing 6 weeks post-partum is required in some cases.
Phone laboratory with specimen queries (523 5731).

Management

Platelet Count (x10⁹)	Action
<30	Transfuse
30-49	Transfuse if any bleeding
50-99	Transfuse if major bleeding
>99	Do not transfuse

If the infant’s platelet count is <30x10⁹/L and the maternal count is normal, the treatment of choice is urgent transfusion of 10ml/kg of matched platelets.
In most cases these will be HPA-1a negative, but Maori and Asian mothers are more likely to have antibodies other than anti HPA-1a.

Infuse platelets over 30-60 minutes (see platelet protocol), and recheck platelet count after one hour.
Antigen-negative platelets should be given urgently, as infants are at significant risk of ICH in the first days of life
If antigen negative platelets are not available, intravenous immunoglobulin (IVIG) 1g/kg/day for 2 days may be effective.
- There is often a delay of 24-48 hours prior to response, leaving a window of risk for ICH.
If the platelet count fails to rise in response to matched platelets consider alternative diagnoses, and check for rarer maternal antibody types.
Affected infants should have a FBC checked daily until platelet count is stable over 100x10⁹/L. Need for platelet transfusion at moderately low platelet counts (30-100 x 109/L) is not clear.
It is essential that parental investigation is initiated prior to discharge and adequate follow up arrangements made.
- The risk of a subsequent pregnancy being affected is 100% if the father is homozygous for the reacting antigen, and 50% if heterozygous.⁴
- In general, subsequent pregnancies are at least as severely affected as the first.
- Antenatal therapy in subsequent pregnancies remains contentious, but options include intrauterine platelet transfusion, maternal immunoglobulin and steroids. ⁵

If you cannot see an index above, please press the "Refresh" button of your browser.

References

1	Williamson, L.M., et al., The natural history of fetomaternal alloimmunization to the platelet-specific antigen HPA-1a (PlA1, Zwa) as determined by antenatal screening. Blood, 1998. 92(7): p. 2280-7.
2	Murphy, M.F., S. Verjee, and M. Greaves, Inadequacies in the postnatal management of fetomaternal alloimmune thrombocytopenia (FMAIT). Br J Haematol, 1999. 105(1): p. 123-6.
3	Management of alloimmune neonatal thrombocytopenia. Lancet, 1989. 1(8630): p. 137-8.
4	Bussel, J.B., et al., Fetal alloimmune thrombocytopenia. N Engl J Med, 1997. 337(1): p. 22-6.
5	Roberts, I.A. and N.A. Murray, Thrombocytopenia in the newborn. Curr Opin Pediatr, 2003. 15(1): p. 17-23.