The components of hemostasis and its regulation from the neonate stage to infancy are similar to those in adulthood, but grow dynamically and conserve a special balance. We present and discuss here these components in the infant from our data and a review of the literature. As already known, all components of the hemostatic and its regulatory system are synthesized by the fetus and do not cross the placenta from the mother. The plasma levels of vitamin K-dependant coagulation proteins and the contact factors in the neonate are one-half or one-third of those in adulthood, but the levels of the cofactors of the coagulation, such as factors V and VIII are almost the same as those in the adult. The inhibitors of the coagulation proteins, such as antithrombin III, heparin cofactor II, protein C and protein S, also show low plasma levels at birth, ranging from 50 to 60% of the levels in the adult, but the plasma level of α₂-macroglobulin is normal or high, and both the main fibrinolytic zymogen, plasminogen, and the main antifibrinolytic factor, α₂-plasmin inhibitor, exist of low levels in the neonate and during early childhood but the plasma level of α₂-plasmin inhibitor is higher than that of plasminogen. These findings indicate that the hemostatic system and its regulatory system in infants grows, maintaining a special balance of components of hemostasis which is different from that in adults, and that the capacity to regulate hemostasis in infants is smaller than that in adults, explaining why serious hemorrhagic or thromboembolic complications tend to occur easily under pathological conditions.

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We report two patients who underwent allogenic bone marrow transplantation from their respective sibling donors who were matched in terms of HLA typing, red cell group antigens and sex. Erythropoietic engraftment was confirmed by the analysis of red cell enzyme. Subjects : Case 1 was a patient who had acute myelogenous leukemia (FAB : M2) in the stage of the first remission and whose donor was her elder sister. Case 2 was a patient who had erythroleukemia (FAB : M6) in the stage of the first remission and received bone marrow transplantation from her younger sister as the donor. Methods : For analysis of red cell enzyme, isoelectric focusing (IEF) polyacrylamide gel electrophoresis (PAGE) was used for esterase D (ESD), and IEF starch gel electrophoresis for phosphoglucomutase (PGM1). Results : Differences were seen in the type of red cell enzyme before transplantation in both patients as follows : In Case 1, the pattern of ESD was classified as type 2-1 for the patient and as type 2 for the donor. In Case 2, the PGM1 pattern was type 1A2A for the patient and type 1 A for the donor. After transplantation, the type of red cell enzyme changed to show the chimeric phenomenon at 1 to 1.5 months, with complete alteration to each donor's red cell enzyme type at 2 months after transplantation. Thus, the analysis of red cell enzyme revealed that the erythropoietic engraftment is delayed about 1 month as compared to that of the leukopoietic system. It was indicated from these results that this analysis is valuable for confirmation of erythropoietic engraftment in bone marrow transplantation from donors matched in terms of red cell group antigens and sex.

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Red cells from 13 children with pure red cell aplasia (PRCA) were examined for reactivity of peanut lectin (PNA, Arachis hypogaea) and blood group antigen, and were analyzed for features of erythrocytic membrane glycoproteins. In several tests with PNA, a positive reaction was seen persistently with red cells from 5 children with congenital chronic PRCA, namely Diamond-Blackfan anemia (DBA) under treatment with corticosteroid without blood transfusion. In 5 reactive children with PRCA, the reaction was not affected by 0.05% polybrene but disappeared after treatment with papain. In these reactive patients with PRCA, no reaction was seen with lectins except for PNA nor polyagglutination was observed. From these findings, the reaction was considered to be caused by Th-activated red cells. The findings of SDS-polyacrylamide gel electrophoresis (SDS-PAGE) in these reactive children did not reveal any abnormality in the glycoproteins of red cell membranes. As to antigen activity of each blood group, similar to cord blood the positive reaction was seen for anti i antibody, while no abnormality was found for other antigens. With red cells from reactive DBA patients, positive reactions were seen in a ring-like shape by the method using FITC-labeled PNA. In addition, positive results were obtained in cytoplasma by the enzyme immunohistochemical staining with BFU-E colony-forming erythroblasts. These results suggest that the reactivity of red cells from DBA against PNA is attributable to abnormal structures of the surface sugar chains that are already present on the membranes at the stage of erythroblasts in bone marrow.

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Usefulness of a subcutaneous (s. c.) administration of KRN8601 (rhG-CSF ; recombinant human granulocyte colony-stimulating factor) was evaluated in the treatment of neutropenia in 18 pediatric patients with aplastic anemia. The patients received KRN8601 at a dose of 2001ag/m² (s. c.) once a day for 4 weeks. Significant elevation of neutrophil counts was observed in 16 of the 18 cases (88.9%). Three patients showed an increase of hemoglobin and platelet counts as well as neutrophil counts. No severe adverse effects were noted in relation to the subcutaneous drug administration. Based on these observations, KRN8601 (s. c.) is considered to be useful for neutropenia in aplastic anemia.

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We herein describe a case of a 16-year-old boy with chronic, presumably perinatally acquired, hepatitis B virus (HBV) infection, diagnosed with chronic active hepatitis on liver biopsy. Subsequently, this child developed pancytopenia, gammopathy, and positive autoimmune markers. No serologic evidence of other viral infection, in particular Epstein-Barr virus or cytomegalovirus, was found. Bone marrow biopsy revealed hemophagocytosis. This child's hematologic abnormality partially responded to steroid therapy. To the long list of protean disease manifestations associated with HBV infection, we have added infection-associated hemophagocytosis.

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We described two cases with hypereosinophilic syndrome. A 14-year-old girl (patient 1) was admitted because of elevation of transaminases (GOT, 515K-U ; GPT, 416K-U). Her total peripheral WBC count was 9, 900/μl (Eos ; 655 /μl). The eosinocyte counts gradually increased to the level of 10, 610/μl. Her pleural effusion and ascites were noted by chest X-P together with ultrasonography. In her ascites, many eosinocytes were shown cytologically. She was treated with prednisolone. Following this treatment, her clinical symptoms subsided. A 6-month-old boy (patient 2) was admitted with generalized rash and failure to thrive. On admission, his peripheral WBC count was 46, 140/μl (Eos ; 19, 380/μl). The liver scintigram using ^99mTc-Sn colloid showed multiple defects and liver biopsy showed infiltration of eosinocytes. He was also treated with prednisolone, and then his clinical condition improved. Both ultrasonography and scintigraphy were useful for diagnosis and clinical evaluation, according to the experience of our cases.

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Recomibinant human granulocyte colony-stimulating factor (rhG-CSF) can exert beneficial effects on many diseases with neutropenia. The usual method of administration of rhG-CSF is daily injection, which may be unsuitable for outpatients. We report herein the clinical efficacy of the twice-weekly treatment with rhG-CSF in a boy with chronic benign neutropenia of childhood (CBN). He had been suffering from recurrent severe stomatitis and perianal abscess. His absolute neutrophil counts in the peripheral blood were less than 250 cells/μl. Bone marrow aspiration revealed a remarkable decrease in the percentage of mature segmented form neutrophils, in spite of a increase in the percentage of neutrophil progenitors to the band form cell stage. Numbers of mature neutrophils in the peripheral blood increased when he was given rhG-CSF in a dose of 50 μg/m²/day for eight consecutive days. Then, we attempted twice-weekly subcutaneous injections of rhG-CSF at a dose of 75 μg/m². Absolute mature neutrophil counts in the peripheral blood increased remarkably on the day after the injection, and decreased below 1, 000 cells/μl on the fourth day. He has not experienced apparent bacterial infections for about one year after the start of the intermittent administrations of rhG-CSF. We concluded that the twice-weekly treatment with rhG-CSF can prevent bacterial infections sufficiently in patients with CBN.

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Attention has been drawn to a pathogenetic relationship between an 8 ; 21 translocation and granulocytic sarcoma in a considerable number of reports on acute myelogenous leukemia (AML) with this association. We report a new patient, and the clinical features of AML with an 8 ; 21 translocation manifested granulocytic sarcoma are analyzed in 53 patients to find a clue for treatment. A 13-year-old patient had developed granulocytic sarcoma in the left mastoid at 6 years after the first remission of AML with an 8 ; 21 translocation. He complained of headache without any abnormal neurological findings. Though the second remission was attained by chemotherapy, the tumor relapsed. Of the 53 patients reviewed, about 80% were less than 40 years of age with a male-to-female ratio of 3.8 : 1. The majority of the patients had FAB M2 subtype, and a missing sex chromosome was found in about 60%. About 75% of the tumors were located in the head or spine. The prognosis seems not so favorable. If patients with AML are identified as having an 8 ; 21 translocation, the existence of granulocytic sarcoma should be excluded by a magnetic resonance imaging scan and a scintigraphy. Clinical studies are required to clarify the effects of total craniospinal radiation for prevention of granulocytic sarcoma and bone marrow transplantation for treatment of already manifested granulocytic sarcoma.

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We reported a case of acute lymphoblastic leukemia (ALL) who developed multiple intestinal perforations during remission induction therapy. A 2-year-old boy diagnosed with ALL (FAB : L2) was admitted in our hospital for induction therapy with vincristine, pirarubicin, prednisolone and L-asparaginase. The first 2 weeks of therapy were uneventful. On day 15, he developed high fever and abdominal pain without any sign of abdominal rigidity. At that time, his peripheral blood film showed an absence of granulocytes. On day 24, his condition further deteriorated with severe abdominal pain, a point of rebound tenderness at the right iliac fossa and other signs of peritonitis. A laparotomy was performed which revealed three perforated lesions along the wall of the ascending colon. Histopathological examinations of the tissue samples from the lesions showed necrosis with infiltration of inflammatory cells but no leukemic cells were seen. The postoperative recovery of the patient was satisfactory and he is on maintenance therapy with bone marrow remission to date. We should always consider that neutropenia during chemotherapy for ALL is one of the risk factors for developing neutropenic enterocolitis.

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Secondary acute non-lymphocytic leukemia (ANLL) developed in a boy with leiomyosarcoma during combined chemotherapy including doxorubicin, cisplatin, actinomycin D, vincristine, vindesine and cyclophosphamide after 17 months from the beginning of therapy for leiomyosarcoma. Although he had not been treated with etoposide or teniposide, the clinical and cytological characteristics of ANLL resembled the etoposide-related secondary leukemia ; i. e., M5a by FAB classification, abnormal karyotype consisted of t (9p-; 11q+), and short latent period until the development of secondary ANLL. After the diagnosis of the ANLL, he received intensive chemotherapy with little effect, and died 5 months later. Considering this case, the combination of cyclophosphamide, cisplatin and topoisomerase II inhibitor such as doxorubicin, actinomycin D may induce secondary leukemia resembling the etoposide-related ANLL.

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We describe a case in which administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) might play a part in blast increase. The patient was a 14 year-old girl diagnosed with aplastic anemia at 3 years of age. Blasts were observed in peripheral blood (1-2%) and bone marrow (13.4%) at the age of 13 and treatment with intravenous rhG-CSF (250-1250, μg/day) was initiated 10 months ago. Blasts were shown to have increased in a peripheral blood smear taken 6 weeks ago. She was referred to our university hospital in May, 1992. Hematologic examinations revealed a leukocyte count of 4, 900/, μl, with 1% neutrophils, 30% lymphocytes and 69% myeloblasts, and the platelet count was below 1, 000/, μl. Bone marrow examination showed a proliferation of myeloblasts (90%), designated as M1 morphology according to the French-American-British classification. Administration of rhG-CSF was stopped. Consequently, sLDH and blasts in peripheral blood and bone marrow decreased naturally and we presume that rhG-CSF triggers the abnormal increase of myeloblasts. The administration of rhG-CSF in myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) patient with a fatal infection is benefical, but caution should be observed to see if myeloblasts increase or not.

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A 7-week-old boy suffered from fever of unknown origin, followed by aseptic meningitis, liver dysfunction, and acute renal failure. On admission, anuria due to acute renal failure, exanthema, and hepatomegaly appeared. His peripheral blood counts showed pancytopenia as follows : WBC 1, 600/μl. Hb 9.0 g/ dl, PLT 9.6×10⁴/μl. The bone marrow examination revealed an increase of hemophagocytic histiocytes with mature forms. The serum ferritin level was elevated to 4, 232 ng/ml. The virus antibody titer suggested cytomegalovirus infection. The diagnosis of cytomegalovirus-associated hemophagocytic syndrome (CMVAHS) was made. Complete remission was obtained after CAPD (continuous ambulatory peritoneal dialysis) and γ-globulin administration following exchange transfusion. The-renal dysfunction, which is reported to be caused by TNF and/or IL-2, is one of the poor prognostic factors. Of particular interest is that a 7-week-old infant with CMV-AHS developed acute renal failure at the early stage without other organ failures.

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