Maternal anti-HPA-1a alloantisera cause severe fetal and neonatal thrombocytopenia. (A) Pre-immunized WT BALB/c mice bred with APLDQ males give birth to severely thrombocytopenic pups. Shown are the platelet counts (mean ± standard error of the mean [SEM]; n = 3-10 mice per group) of neonatal pups 48 hours after birth from 3 representative BALB/c females that had been pre-immunized with APLDQ platelets. Although litter sizes were normal to near normal, all of the newborn pups were nearly devoid of circulating platelets. Control 1: platelet counts of pups derived from a female BALB/c mouse that had not been pre-immunized with APLDQ platelets before breeding with an APLDQ C57BL/6 male. Control 2: platelet count of pups derived from WT BALB/c females that had been pre-immunized with platelets from an APLDQ-expressing C57BL/6 mouse before being bred with a WT C57BL/6 male. Note that alloantibodies produced as a result of the difference in class I MHC molecules between the 2 strains of mice (supplemental Figure 2) result in neither thrombocytopenia nor FNAIT, much the same as in humans. (B) Maternal antibody levels correlate inversely with fetal platelet count. Maternal blood samples were collected on day 19.5 of gestation and subjected to flow cytometric analysis against APLDQ C57BL/6 murine platelets. Fetuses were collected in parallel, the blood of littermates was pooled, and the platelet count of each pool was determined. Each data point represents the average platelet count of a single litter. **P < .001.