Throughout four decades of research, much has been learned about each coagulation factor and its activation process and regulation. However, the mechanism by which these proteins interact with each other in blood (on platelets or endothelial cells) to form blood clots is still not clear. This review describes the current knowledge of the structural and functional properties of vitamin K-dependent coagulation factors, after a simplified description of the mammalian coagulation cascade.

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In North America and Western Europe, the Nurse Coordinator (NC) plays an important role as key person in solving the variety of problems faced by hemophiliacs and their families. Actually, NCs are playing active roles at North Kyushu Hemophilia Center (NKHC). The main activities of the NCs at NKHC are providing a link between hemophiliacs and the whole team, educating patients in the basics of hemophilia and home infusion and giving advice and offering support for medical, emotional, social and other issues. On the other hand, our country is very slow in introducing NCs for total care of hemophiliacs. Therefore, surveys of nurses and doctors were conducted to clarify the reason for delayed introduction of NCs in Japan. A survey of hemophiliacs and their families was also conducted to clarify the role of the nurse in Japanese hemophilia care. These results indicate that introduction of NCs in Japan is far behind that in other developed countries because of a variety of problems on the nursing side such as qualifications, treatment, training system and frequent transfer of the nurse, although nurses, doctors and patients hope to introduce NCs for hemophilia care.

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The cytotoxic effects of 6-mercaptopurine (6MP) therapy in children show wide variation. A major factor that influences the formation of 6-thioguanine nucleotides (6TGN), which are cytotoxic metabolites of 6M13, is S-methylation which catalyzes 6MP to 6-methylmercaptopurine nucleotides (6MMPN). A total of 33 blood samples were obtained from 6 children, who continuously received 6MP orally for 5-231 (median 72) days. The non-methylated metabolite, 6TGN, and the methylated metabolite, 6MMPN, were measured simultaneously in red blood cells. The ratio of 6MMPN to 6TGN was considered to be related to the degree of S-methylation. The concentrations of 6TGN and 6MMPN varied widely. No subject showed a low concentration of these metabolites that would reflect poor compliance. Wide differences in the ratio of 6MMPN to 6TGN were found among individuals, range from 1.7 to 43.4. However, the ratio was constant in individual children. The simultaneous measurement of 6TGN and 6MMPN concentrations in red blood cells may help to identify pediatric patients who are receiving a suboptimal dose of 6MP.

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Juvenile myelomonocytic leukemia (JMML) is a well-characterized malignant hematopoietic disorder in early childhood. Onset age above 2 years, thrombocytopenia, high HbF value and cytogenetic abnormalities are known to be poor prognostic factors. However, there currently exist no readily available laboratory markers that reflect disease activity. While blast transformation of peripheral blood mononuclear cells stimulated by concanavalin A or phytohemagglutinin is widely used to evaluate immune function, attention is seldom paid to the control (without mitogen) values which indicate the level of spontaneous blast formation (SBF). During the treatment of three cases of JMML, we found SBF values, significantly high at diagnosis, to be a good marker of disease activity where clinical exacerbation or improvement was associated with a change in SBF values. Determination of the SBF values appears to be a good marker of JMML activity, although its evaluation is warranted in a large study.

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We report here a case of scleroderma with fasciitis which developed as chronic graft-versus-host disease (GVHD) at 22 months post bone marrow transplantation (BMT). The patient, who had been treated for T-cell non-Hodgkin's lymphoma at age 14, received transplantation from his HLA-identical brother during the second complete remission at age 15. Acute GVHD grade II of the skin and gut with protein-losing enteropathy was resolved with methylprednisolone pulse therapy, switch of CsA to taclorimus (FK506) and with mesalazine. After 18 months from BMT he became free from prednisolone and FK506. Three months later, he complained of fatiguability and stiffness of the upper and lower limbs, and gradually showed sclerodermatous changes of the skin. Muscle contraction became apparent leading to arthrogryposis of bilateral knees and elbows. According to the clinical and histological findings, the patient was diagnosed as sclerodermatous chronic GVHD. Despite readministration of immunosuppressants, he showed progression of sclerodermatous changes ; therefore, he was placed on methylprednisolone pulse therapy and antithymocyte globulin, but the disease could not be resolved. At thirty months after BMT, etretinate was effective, which resulted in partial remission ; however scleroderma and muscle contraction were refractory. Novel therapies for this kind of refractory GVHD are awaited.

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A one-year-old boy with severe neutropenia during primary Epstein-Barr (EB) virus infection was encountered. Agranulocytosis without atypical lymphocytosis and pancytopenia was seen at the first stage. Typical infectious mononucleosis (IM) and hemophagocytic syndrome (HPS) were not demonstrated. A bone marrow aspiration showed a myeloid maturation arrest. Granulocyte colony stimulating factor (G-CSF) was effective to elevate the neutrophil count and improve the clinical symptoms. This case is reported because previous reviews of literature cited only a few cases of such agranulocytosis in association with EB virus infection.

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