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Immunization against the human platelet antigen (HPA)-1 alloantigen is the most common cause of severe fetal and neonatal thrombocytopenia. Fetal therapy has substantial risks and its indications need better definition. Of 24,417 consecutive pregnant women, 618 (2.5%) were HPA-1a negative of whom 385 entered an observational study. All were HLA-DRB3*0101 genotyped and screened for anti–HPA-1a. Their partners and neonates were HPA-1 genotyped and the latter were assessed by cord blood platelet counts and cerebral ultrasound scans. Anti–HPA-1a was detected in 46 of 387 pregnancies (12.0%; 95% CI 8.7%-15.2%). All but one were HLA-DRB3*0101 positive (odds ratio 140; 95% CI 19-1035;P< .00001). One baby died in utero, and of 26 HPA-1a–positive babies born to women with persistent antenatal antibodies, 9 were severely thrombocytopenic (8 with a count <10 × 109/L, 1 with a large porencephalic cyst), 10 were mildly thrombocytopenic, whereas 7 had normal platelet counts. Severe thrombocytopenia was significantly associated with a third trimester anti–HPA-1a titer = 1:32 (P = .004), but was not observed in babies of women with either transient or postnatal-only antibodies. HPA-1a alloimmunization complicates 1 in 350 unselected pregnancies, resulting in severe thrombocytopenia in 1:1,200. HPA-1a and HLA-DRB3*0101 typing combined with anti–HPA-1a titration allows selection of the majority of pregnancies at risk of severe thrombocytopenia.

A number of chemically distinct anxiolytics were examined for effects on defensive behavior (foot-shock-induced freezing) in rats. Central nervous system acting drugs which are not anxiolytics were also studied. Animals were injected with a drug or vehicle (IP) prior to being placed in a chamber with a grid floor through which two footshocks were delivered. Behavior was observed during the pre-shock period (2 min) and for 4 min after the second footshock. The effects of the following drugs on the duration of footshock-induced freezing were studied: diazepam (DZP); 2-amino-4,5-(1,2-cyclohexyl)-7 phosphonoheptonic acid (NPC 12626); 3-((+/−)-2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid (CPP); [(+)-5-methyl-10-11,dihydroxy-5H-dibenzo(a,d)cyclohepten-5,10-imine (MK-801); buspirone hydrochloride (BUS);dl-amphetamine sulfate (AMP); haloperidol (HAL); ethyl-β-carboline-3 carboxylate (β-CCE). Compounds which reduced the duration of footshock-induced freezing included DZP, BUS, and the competitive NMDA antagonists NPC 12626 and CPP. The non-competitive NMDA antagonist, MK-801, had no effect on the response. The highest dose of amphetamine tested also reduced footshock-induced freezing. However, amphetamine-treated animals did not locomote or rear after footshock, suggesting fear of the environment. Animals injected with DZP, NPC 12626, CPP or buspirone spent at least 1.4 of the 4 post shock minutes locomoting. Haloperidol had no effect on freezing at the doses tested. β-CCE tended to increase the duration of footshock-induced freezing. With the exception of buspirone, none of the compounds which reduced freezing were analgesic in a hot plate test, suggesting that analgesia was not the cause of reduced freezing. Foot-shock-induced freezing is a simple test which may be useful for detecting the anxiolytic potential of drugs from a number of different classes.