From concept to practice: Screening for fetal and neonatal alloimmune thrombocytopenia (FNAIT).

Severe neonatal thrombocytopenia due to fetomaternal anti-A alloimmunization: A case report

Petechiae or echymoses and severe thrombocytopenia (< 20 × 109 platelets/litre) is a worrying and serious condition in newborn infants. Rapid correction of the platelet count is essential to prevent...

A 27-year-old G3A2L0 woman is referred to the Maternal Fetal Medicine clinic after a routine third-trimester ultrasound in a community setting shows an intracerebral mass at 30 weeks’ gestational age (GA). The mother is healthy other than being a chronic carrier of hepatitis B. She is blood type B positive with a negative antibody screen. She previously had two first-trimester therapeutic abortions, and this is her first pregnancy with her current partner. The pregnancy was uneventful with a negative integrated prenatal screen and ultrasounds with normal results at 14 and 20 weeks’ GA. Mild maternal thrombocytopenia was detected throughout the pregnancy (lowest platelet count 97 × 109/L) with reported increased bruising. There is no family history of bleeding disorders in either her or her partner's family. The findings on physical examination are normal with no signs of bleeding, bruising, or petechiae. A complete blood cell count shows a hemoglobin level of 11.3 g/dL (113 g/L) and a platelet count of 124 × 103/μL (124 × 109/L). A repeat ultrasound confirms a large complex intracerebral mass with hypoechoic areas suggestive of cysts as well as echogenic portions that were felt to be either solid or to represent bleeding with clots. The composition of the mass is clarified by maternal MRI at 31 weeks’ GA, which shows a large cystic complex lesion measuring 5.0 × 3.8 × 4.5 cm (Fig 1). There is a solid component that shows blooming on the susceptibility-weighted imaging sequence, suggestive of blood products, clot, or calcification, but an underlying neoplastic process or vascular anomaly cannot be excluded. Figure 1. MRI of the maternal pelvis at 31 weeks’ GA without gadolinium. Large complex cystic lesion (arrow) in the frontoparietal region of the left cerebral hemisphere of the fetus with characteristics suggestive of blood products. …

Massive fetal hemorrhage and fetomaternal alloimmune thrombocytopenia from human platelet antigen 5b incompatibility: an unusual association

Fetal and neonatal alloimmune thrombocytopenia in 2022: a response

Fetal and neonatal alloimmune thrombocytopenia

Are HPA-5b antibodies a significant cause of FNAIT and associated bleeding or merely an incidental finding?

Neonatal alloimmune thrombocytopenia is a rare (1/1000–5000 births) life-threatening disorder, caused by fetomaternal incompatibility for a fetal human platelet alloantigen inherited from the father, with production of maternal alloantibodies against...

Fetal bradycardia following intrauterine platelet transfusion: might elevated levels of donor soluble CD40 ligand play a role?

While neonatal alloimmune thrombocytopenia (NAIT) is the most common cause of severe neonatal thrombocytopenia good clinical predictors are lacking. We analyzed cases of neonatal thrombocytopenia in Schneider Children's Medical Center of Israel to pinpoint qualifiers of NAIT (NAIT+) in comparison to non-NAIT (NAIT-) thrombocytopenia. Patient and maternal data were retrospectively collected on all thrombocytopenic newborns undergoing a workup for NAIT in our tertiary center between 2001 and 2016. Among 26 thrombocytopenic neonates, the mean nadir in NAIT+ patients (25×10 9 /L) was significantly lower than NAIT- patients (64×10 9 /L) ( P <0.001). 61.5% of NAIT+ infants required treatment compared with 23% of non-NAIT ( P =0.015). NAIT+ patients also required more therapeutic modalities than infants with NAIT- thrombocytopenia. Human platelet antigen (HPA)-1a and HPA-5b alloantibodies most frequently caused NAIT. In summary, thrombocytopenia in NAIT+ was significantly more severe compared with NAIT- and more likely to require treatment. In addition, despite the varied ethnic population in Israel, the HPA alloantibodies found in our population were most similar to those common in Western countries. In the absence of rigorous prenatal screening options, we suggest platelet counts below 40 to 50×10 9 /L in a healthy newborn be considered most suggestive for NAIT and warrant urgent NAIT-specific analysis.

A screening and intervention program aimed to reduce mortality and serious morbidity associated with severe neonatal alloimmune thrombocytopenia

Fetomaternal alloimmune thrombocytopenia (FMAIT) is the commonest cause of severe thrombocytopenia in term neonates but its management remains controversial. A 7-year prospective observational study of 200 cases of FMAIT evaluated the relationship between human platelet antigen (HPA) antibody specificity, clinical presentation, morbidity, mortality, and therapeutic interventions in the antenatal and postnatal period, with long-term follow-up of neonates with intracranial hemorrhage (ICH). In 1148 referrals for FMAIT, HPA antibodies were confirmed in 200 (17%). The commonest specificities were anti-HPA-1a, 150 (75%); anti-HPA-5b, 31 (15.5%); and anti-HPA-15b, 8 (4%). Of 123 (62%) cases (two sets of twins) with no previous history of FMAIT, intrauterine deaths occurred in 5: anti-HPA-1a alone, 3; in combination with anti-HPA-5b, 1; and anti-HPA-15b, 1. Of the 120 live neonates, 103 had severe thrombocytopenia and 17 (14%) developed ICH (anti-HPA-1a, 13; anti-HPA-5b, 3; anti-HPA-15b, 1). Postnatal care varied widely with 37 percent of neonates receiving random rather than HPA-1a and -5b-negative platelets. Of the remaining 77 cases with a history of FMAIT, 40 received intrauterine transfusions. Six (15%) of these fetuses died in utero and an additional 2 developed ICH postnatally. Of the 19 children with ICH, 1 (anti-HPA-15b) died on Day +1, and neurologic sequelae persist in 13 (mean follow-up, 2.5 years). HPA-1a antibodies are most commonly implicated in severe thrombocytopenia but HPA-5b and HPA-15b antibodies can also result in poor outcome. Postnatal transfusion management is extremely variable, and fetal transfusions are associated with significant morbidity and mortality.

Identifying Pregnancies at Higher Risk for HPA-1a Alloimmunization and Fetal/Neonatal Alloimmune Thrombocytopenia (FNAIT): An International, Prospective, Natural History Study

Neonatal alloimmune thrombocytopenia (NAIT) is a common but significant challenge for neonatologists and a potentially devastating disease that may lead to intracranial bleeding. The underlying mechanism of thrombocytopenia is expected to be mediated by accelerated clearance of antibody-opsonized fetal platelets. We report severe recurrent NAIT related to human platelet antigen (HPA)-15 systems in 2 consecutive siblings. The first child presented with intracranial hemorrhage at birth and subsequently died. The diagnosis of NAIT, although initially suspected, was ruled out after negative investigation of only HPA-1, HPA-3, and HPA-5 systems. The second child experienced a clinically milder presentation but a profound thrombocytopenia. In both siblings, NAIT was unexpectedly associated with amegakaryocytosis, suggesting that alloimmunization could extend at the megakaryocyte level. In addition, both siblings presented with drastic abnormalities in the B-cell compartment, which led to broad investigations for an immune-deficiency syndrome and provided a novel pathophysiologic hypothesis. Both placental examinations revealed major lymphoid infiltration involving the villous placenta, which is consistent with the diagnosis of villitis of unknown etiology. Severe thrombocytopenia in an otherwise healthy newborn should raise high the suspicion of NAIT. The diagnosis of NAIT should not be ruled out until extensive human platelet antigen systems have been investigated to screen for fetal-maternal antigen incompatibility. This is crucial not only for the newborn to allow optimal lifesaving treatments but also for effective management of future pregnancies. Interestingly, antibodies to HPA-15 have previously been reported with severe NAIT-related thrombocytopenia, but we are the first to report associated in vivo amegakaryocytosis.

Neonatal alloimmune thrombocytopenia (NAIT) is a potentially devastating disease that may lead to intracranial hemorrhage in the fetus or neonate, often with death or major neurologic damage. There are no routine screening programs for NAIT, preventive measures are taken only in a subsequent pregnancy. To estimate the population incidence of NAIT and its consequences, we conducted a review of the literature. Our results may aid in the design of a screening program. An electronic literature search included Medline, Embase, Cochrane database and references of retrieved articles. Eligible for inclusion were all prospective studies aimed at diagnosing NAIT in a general, nonselected newborn population, with sufficient information on platelet count at birth, bleeding complications, and treatment. Titles and abstracts were reviewed, followed by review of full text publications. Studies were independently assessed by 2 reviewers for methodologic quality. Disagreements were resolved by consensus, including a third reviewer. From the initial 768 studies, 21 remained for full text analysis, 6 of which met the inclusion criteria. In total, 59,425 newborns were screened, with severe thrombocytopenia in 89 cases (0.15%). NAIT was diagnosed in 24 of these 89 newborns (27%). In 6 (25%) of these cases, an intracranial hemorrhage was found, all likely of antenatal origin. NAIT is among the most important causes of neonatal thrombocytopenia. Intracranial hemorrhage due to NAIT occurs in 10 per 100 000 neonates, commonly before birth. Screening for NAIT might be effective but should be done antenatally.