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Background: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is caused by anti-HPA alloantibody, and anti-HPA-4b is the most common cause in Japanese. Anti-HPA-5b is frequently detected in pregnant women, but it is still controversial whether anti-HPA-5b causes severe FNAIT., Case Presentation: A Japanese woman with anti-HPA-4b and anti-HPA-5b alloantibodies delivered a baby with severe FNAIT who was both HPA-4b and HPA-5b incompatible. We carefully monitored the patient's following three pregnancies (the second and the fourth siblings were HPA-4b incompatible and HPA-5b compatible; the third sibling was both HPA-4b and HPA-5b compatible). FNAIT was not observed in all three siblings, although a modest decrease in cord blood platelet count was observed in the HPA-4b incompatible siblings compared to the HPA-4b compatible sibling. Serial monitoring of anti-HPA titer showed that anti-HPA-4b markedly decreased in late pregnancy and recovered after delivery of the HPA-4b incompatible siblings, but these decreases were not observed during the mother's pregnancy with the HPA-4b compatible sibling. In contrast, anti-HPA-5b remained at a high titer during pregnancy with all three siblings., Conclusion: Our data indicate that dynamic changes of anti-HPA-4b occur during pregnancy and strongly suggest that anti-HPA-5b was mainly responsible for severe FNAIT in this case., (© 2023. Japanese Society of Hematology.)

The rare blood phenotype D-- is characterized by the absence of RhCcEe antigens. Women with this blood type who have experienced previous pregnancies may produce anti-Rh17 antibodies, which may cause severe fetal hemolytic anemia or fetal death in subsequent pregnancies. We report successful management of a pregnancy associated with fetal hemolytic disease owing to high titers of anti-Rh17 (1:4096) in a woman with a history of a pregnancy with fetal hydrops and intrauterine fetal death. During her second pregnancy, she received two sets of plasma exchange (PE) per week from weeks 12 till 20. Intrauterine transfusions (IUTs) were performed at 26, 27, 29, and 31 weeks. A male infant was born at 32 weeks and 4 days by normal vaginal delivery, with a birth weight of 1916 g (+ 0.16 SD). He received an exchange transfusion on day 0, immunoglobulin (intravenous immunoglobulin: 1 g/kg) on days 0 and 1, and photo therapy from days 0 to 6. He showed normal development without neurological abnormality and was discharged from the hospital on day 36. We successfully prevented complications caused by the presence of anti-Rh17 antibodies in the mother during pregnancy. The IUT and maternal PE may have promoted this favorable outcome.

We consecutively examined the utility of measurements of percentage of immature platelet fraction (IPF%) and absolute IPF number (A-IPF) in predicting thrombopoietic recovery in 15 adult patients who underwent allogeneic hematopoietic stem cell transplantation (allo-SCT). Four patients were excluded from the evaluation due to insufficient data. Platelet count and IPF were measured by Sysmex XN-1000 (XN), a newer generation analyzer. First, we confirmed that platelet count measured by XN was more accurate than by XE-2100 (XE). IPF measurement was effective to predict the recovery in 7 of the 11 patients examined. Moreover, IPF measurement, especially IPF% measurement, suggested accelerated platelet turnover in two patients who failed to achieve platelet recovery by day 60. In addition to IPF%, A-IPF showed a complementary role on the prediction of thrombopoietic recovery. The increase in IPF% was only transient, while A-IPF values showed lasting increase during platelet recovery. In two patients (cases 6 and 7) an increase in A-IPF, but not in IPF%, was observed during platelet recovery. Our data suggest that IPF% and A-IPF measured by XN are useful for the prediction of thrombopoietic recovery and the assessment of pathogenesis of thrombocytopenia in patients after allo-SCT.

The diagnosis of primary immune thrombocytopenia (ITP) is based on differential diagnosis. Although the measurement of percentages of reticulated platelets (RP%) by flow cytometry is useful as a supportive diagnostic test, this method is nonetheless a time-consuming, laboratory-based assay. To identify alternative assays that are useful in daily practice, we compared three methods in parallel, IPF% measured by XE-2100 [IPF% (XE), Sysmex Corp.], IPF% measured by new XN-1000 [IPF% (XN)], and RP%. We examined 47 patients with primary ITP, 28 patients with aplastic thrombocytopenia (18 aplastic anemia and 10 chemotherapy-induced thrombocytopenia) and 80 healthy controls. In a selected experiment, we examined 16 patients with paroxysmal nocturnal hemoglobinuria (PNH) to examine the effect of hemolysis. As compared with IPF% (XE), IPF% (XN) showed better within-run reproducibility. The sensitivity and specificity for the diagnosis of ITP were 83.0 and 75.0 % for IPF% (XE), 85.1 and 89.3 % for IPF% (XN), and 93.6 and 89.3 % for RP%, respectively. Examination of PNH patients revealed that hemolysis and/or red blood cell fragments interfered with IPF% (XE) values, but not with IFP % (XN) values. Our results suggest that IPF% measured by XN-1000 may be of comparable value with RP% as a supportive diagnostic test for ITP.

Neonatal alloimmune thrombocytopenia (NAIT) is induced by maternal alloantibodies raised against fetal platelet antigens inherited from the paternal parent. In contrast to Caucasians, in Asians, predominantly in Japanese, most frequently detected antibodies in NAIT are anti-HPA-4b and anti-HPA-5b. In some NAIT cases multiple alloantibodies are detected. In such cases it is very difficult to determine which antibody is the dominant antibody in NAIT. In this case report, we describe a NAIT case (first sibling) with severe thrombocytopenia and cephalhematoma in the presence of both anti-HPA-4b and anti-HPA-5b antibodies in the maternal serum. We carefully examined titers of anti-HPA antibodies during the subsequent pregnancy with HPA-4b-positive and HPA-5b-negative fetus determined by amniocentesis at gestational week 16. We administered IVIG (1 g/kg/w) to the mother from gestational week 32 to 35. The mother subsequently delivered a second sibling with normal platelet count by cesarean section. Although we could not completely rule out the involvement of anti-HPA-4b, our findings suggested that anti-HPA-5b was implicated in the NAIT in the first sibling.

TEL is a new member of the ETS-like family on chromosome 12 and forms fusion genes with several partners in leukemia. Among these fusion genes, the TEL/AML1 translocation resulting from t(12;21) is found in approximately one quarter of the childhood B-cell lineage acute lymphoblastic leukemia (ALL) cases and its prognosis is excellent. We examined 42 adult patients with B-cell lineage ALL and 13 adult patients with lymphoblastic transformation of chronic myeloid leukemia (CML) to detect TEL/AML1 fusion genes using the reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blotting, but no translocation was detected. These findings indicate that absence of the TEL/AML1 fusion transcript partly correlates with the poorer outcome of adult B-cell lineage ALL as compared with childhood ALL and the TEL/AML1 fusion transcript is specific for pediatric B-cell lineage ALL.