Hemostatic balance between pro- and anticoagulant is maintained during glucocorticoid treatment.

BACKGROUND: Glucocorticoids are associated with an increased risk of venous thrombosis. Glucocorticoid treatment increases coagulation factor and anticoagulant levels; however, its effect on hemostatic function remains unclear. This study aimed to investigate the changes in comprehensive coagulation profiles after glucocorticoid treatment in noninflammatory diseases to elucidate the direct contribution of glucocorticoids to hemostatic function. PROCEDURE: Patients diagnosed with primary immune thrombocytopenia requiring glucocorticoid treatment were prospectively enrolled in this study. Changes in coagulation factors and anticoagulants during glucocorticoid treatment and changes in thrombin generation potential were determined in the absence and presence of soluble thrombomodulin (sTM). RESULTS: Seven treatment cases (four for steroid pulse therapy and three for oral glucocorticoid therapy) in six patients with immune thrombocytopenia were examined. After glucocorticoid treatment, activated partial thromboplastin time significantly shortened, and activities of factor VIII, IX, XI, and XII significantly increased, except for von Willebrand factor antigen. Moreover, antithrombin and protein C (PC) activities significantly increased after glucocorticoid treatment. Two major parameters of thrombin generation potential, endogenous thrombin potential (ETP) and peak thrombin (Peak), significantly increased in the absence of sTM after glucocorticoid treatment. However, no significant increases in either parameter were observed in the presence of sTM. ETP-TM and Peak-TM ratios, which represent resistance to the anticoagulant effect of the PC pathway, significantly decreased after glucocorticoid treatment, suggesting that anticoagulant function via the PC pathway is elevated after glucocorticoid treatment. CONCLUSIONS: As glucocorticoids increase intrinsic coagulation factor and anticoagulant levels, hemostatic balance between pro- and anticoagulant functions is maintained.

First case report of hemophilia B Leyden in Japan.

Hemophilia B Leyden is a unique subtype of hemophilia B, characterized by increasing factor IX activity (FIX:C) after puberty and a lower normal range of FIX:C throughout adulthood. However, to date, no Japanese case has been reported. Here, we report a case of hemophilia B Leyden in a 22-year-old male. He suffered from subgaleal hematoma, and was subsequently diagnosed with hemophilia B (FIX:C 0.2%) in the neonatal period. Both his parents are Japanese. There was no history of hemophilia in his family. FIX:C gradually increased with age (8% at age = 1; 14% at age = 7; 19% at age = 12; 32% at age = 18). FIX:C is within the range 30-40% in recent several years. He once required administration of FIX concentrate against traumatic tongue bleeding at 7 years of age. Genotyping analysis of FIX was performed after informed consent at 21 years of age, and a point mutation (c.-35G>A) was detected. This mutation has been reported previously as the Leyden mutation. Although it has been reported that hemophilia B Leyden is seen in 1.9% of patients with hemophilia B, the present case is the first report of hemophilia B Leyden from Japan.

A cohort study of the usefulness of primary prophylaxis in patients with severe haemophilia A.

Primary prophylaxis is a method of haemostatic management to prevent bleeding and arthropathy in patients with severe haemophilia. The aim of this study was to evaluate the usefulness of primary prophylaxis in patients with severe haemophilia A. This study included 15 patients with haemophilia A who received primary prophylaxis at our institution for a minimum of 5 years. We evaluated the annualized bleeding ratio of joints or other sites, current joint function, and X-ray images and MRI scans taken when patients were 6 years old. The range of patients' ages at the end of the study was 6.2-16.8 years, and at the start of primary prophylaxis it was 0.8-2.4 years. Factor VIII concentrates (25-40 units kg(-1) dose(-1)) were administered 3 times/week or every other day, according to the Swedish protocol. Mean joint and non-joint annualized bleeding ratios were 0.49 ± 0.5 and 1.54 ± 1.69, respectively. At the final evaluation, all patients displayed a normal range of motion for both elbows, knees, and ankles. The radiography and MRI findings at the age of 6 were unremarkable in all patients. Overall, primary prophylaxis for patients with severe haemophilia A was performed safely, reduced the number of bleeding events, and prevented progression to arthropathy.

[Efficacy of chemotherapy combined with bortezomib for two cases of relapsed/refractory acute lymphoblastic leukemia].

Bortezomib (BZM), a proteasome inhibitor, was recently reported to be effective against acute lymphoblastic leukemia (ALL). We report two cases of relapsed/refractory ALL, who were treated with BZM (1.3 mg/m2/dose, 2 doses/week for 2 weeks) in combination with vincristine, doxorubicin, dexamethasone, and L-asparaginase (L-ASP). The first patient was a 16-year-old girl who developed a bone marrow relapse 8 months after the initial diagnosis during consolidation chemotherapy. She received BZM-combined chemotherapy without L-ASP considering her previous history of an allergic reaction to L-ASP. The BZM-combined regimen was discontinued due to interstitial pneumonia development on day 13, and the interstitial pneumonia was successfully treated with steroid pulse therapy. Although her elevated serum LDH transiently normalized on day 16, blasts in peripheral blood did not disappear, and she died of leukemia without achieving remission. The second patient was a 17-year-old girl who developed a third bone marrow relapse after cord blood transplantation. She was given the same BZM combined regimen. Although the BZM-combined regimen was discontinued due to acute pancreatitis development on day 12, complete remission without platelet recovery was confirmed on day 62. Our experience suggests not only the effectiveness of BZM-combined chemotherapy but also the importance of controlling its toxicities when administered as a salvage therapy for advanced ALL patients.

T-cell large granular lymphocyte leukemia in a child with anemia and Crohn's disease.

T-LGL leukemia has been rarely reported in children. We report a child with T-LGL leukemia who presented with anemia and went on to develop Crohn's disease. Although prednisolone treatment proved effective in the treatment of anemia, large granular lymphocyte counts increased as the doses were tapered. T-cell rearrangement studies revealed a clonal rearrangement of the TCR Vß/jß2 gene. Concurrently, the patient developed severe diarrhea. Inflammatory changes across the upper and lower intestines led to the diagnosis of Crohn's disease. This case highlights that T-LGL leukemia could be occurred in children. Flow cytometry and/or T-cell gene rearrangement studies are recommend in patients of anemia and various kind of autoimmune diseases including Crohn's disease, even in children.