Transfusion medicine handbook

6. Special Circumstances

6.19 Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT)

FNAIT is a rare but serious condition which arises from maternal alloimmunisation to fetal platelet antigens of paternal origin and which affects approximately 1:1,100 pregnancies. FNAIT is the platelet equivalent of HDFN, where maternal IgG antibodies cross the placenta and may destroy fetal platelets and may destroy fetal platelets, leading to thrombocytopenia and an increased risk of bleeding. The most serious consequence, estimated to occur in 10 - 20% of untreated pregnancies and presenting at any time from 20 weeks gestation until a few days after birth, is intracranial haemorrhage (ICH) which may be fatal or lead to long-term neurological problems.

The most common alloantibody responsible for FNAIT in Caucasians is anti-HPA-1a (80 - 90% of cases) followed by anti-HPA-5b (5 - 15%), with other HPA antibody specificities infrequently seen. In Maori and Asian mothers consideration should be given to other antibodies including those within the HPA-4 system.

There may or may not be a history of thrombocytopenia in a previous infant. Unlike HDFN, FNAIT can occur during a first pregnancy and in fact almost half of the clinically evident cases are discovered in the first live-born infant.

Treatment

The management of FNAIT is overseen by a fetal medicine specialist along with input from a specialist haematologist and/or NZBS Transfusion Medicine Specialist.

In the neonatal period the condition is self-limiting often resolving within two weeks after birth although occasionally persisting for up to eight weeks. The treatment of choice is transfusion of platelets lacking the specific HPA antigen. In the absence of specific HPA antigen negative platelets, random platelets can be used, usually with good effect [20]. In the absence of suitable donor platelets, the mother's platelets may be used. These must be washed to remove the plasma that contains the platelet antibody and must be irradiated. Such a designated donation must follow the usual procedures for collecting, testing, storing, handling and transfusing of the unit that apply to non-selected blood donations.

For well neonates with suspected FNAIT, no evidence of haemorrhage, and where the platelet count is < 30 x 10⁹/L, prompt transfusion of platelets negative for both HPA-1a and HPA-5b antigens is recommended. However, the evidence to support this platelet threshold is very low [21].

Following the results of serological testing, designated donations negative for the implicated antigen are recommended.

Where there is evidence of ICH or other major haemorrhage, a higher platelet threshold 50 - 100 x 10⁹/L should be used (see Table 6.12). Platelets should be transfused to maintain platelet counts initially above 100 × 10⁹/l and then above 50 × 10⁹/l for at least 7 days [21]. In view of the poor outcome of FNAIT-associated ICH, if HPA antigen-negative or washed maternal platelets cannot be provided, transfusion of randomly selected platelets (irrespective of their HPA status) is recommended [18] [20]. Intravenous immunoglobulin (IVIg) is an alternative therapy, although there is often a 24 to 48 hour delay in response, and may be used in combination with platelet transfusion. Treatment of the neonate with high dose intravenous immunoglobulin (2 g/kg body weight) is effective in about 65% of cases and can reduce the period of dependence on compatible platelets.

For women with a history of FNAIT, management of the fetus during a subsequent pregnancy includes assessment of ICH risk (including paternal HPA zygosity +/- fetal HPA genotyping), antenatal administration of IVIg 1 - 2 g/kg/week from as early as 12 weeks, and/or corticosteroids. Despite immune modulating therapy, there remains an increased risk of fetal ICH. For cases considered to be at high risk of ICH (such as a previous child with FNAIT-associated ICH), prophylactic intrauterine fetal platelet transfusions may be included in the management.