Effect of Cytokine Gene Polymorphisms on Eltrombopag Reactivity in Japanese Patients with Immune Thrombocytopenia.

BACKGROUND: Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by low platelet counts resulting from antiplatelet autoantibodies. Analysis of polymorphisms in cytokine-encoding genes is important for understanding the pathophysiology of ITP and selecting appropriate treatments. We investigated associations between polymorphisms in cytokine-encoding genes and responses to therapy in Japanese patients with ITP. METHODS: The participants in this study comprised 153 patients with ITP and 70 healthy controls. We extracted data on sex, age, platelet counts, bleeding symptoms, and therapeutic responses, including those to prednisolone (PSL) and eltrombopag. Genomic DNA was isolated from peripheral blood and polymorphisms in TNF-α, IL-10, TGF-ß1, and IFN-γ genes were analyzed using the PCR-SSP method. RESULTS: Our results showed that the TGF-ß1 +869 C/C genotype might be related to ITP in Japanese patients. The IL-10 -592 C/C and A/A, -819 C/C and T/T, and -1082, -819, -592 ATA/ATA genotypes might be associated with reactivity to PSL. Furthermore, the IL-10 -592 C/A -819 C/T genotypes, IL-10 ACC/ATA genotype, and TGF-ß1 +869 T/T and T/C genotypes might be linked to the response to eltrombopag. CONCLUSION: Our results indicate that analysis of polymorphisms in cytokine-encoding genes could aid in understanding PSL and eltrombopag responsiveness in Japanese patients with ITP.

Analysis of HLA haplotype and clinical factors during hematopoietic stem cell transplantation.

BACKGROUND: The human leukocyte antigen (HLA) haplotype of the recipient in hematopoietic stem cell transplantation (HSCT) is a key factor in its success or failure. We analyzed the relationship between HLA haplotype frequency and associated clinical factors in HSCT patients. METHODS: Patients who underwent allogeneic HSCT between 2000 and 2019 at our institution were enrolled in this study. The HSCT composition was 77 bone marrow transplantations (BMT), 38 peripheral blood stem cell transplantations (PBSCT), and 36 cord blood transplantations (CBT). Patients were classified into three groups according to their donor HLA haplotype frequency in the Japan Population: group A, top 1-10 haplotypes; group B, top 11-100 haplotypes; and group C, haplotype 101-. We then compared various items including clinical biomarkers with the HLA haplotype frequency. RESULTS: A significant negative correlation was identified between older persons and length of survival. There are also significant correlations between survival and levels of immunoglobulin G, D-dimer, and C-reactive protein, as well as the platelet-large cell ratio before transplantation. A total of 96, 30, and 25 patients were classified into groups A, B, and C, respectively. The HSCT match rate was significantly higher in group A patients than in those of groups B and C. In contrast, the death rate, D-dimer level, and length of time for engraftment were significantly higher in group B and C patients than in those of group A. CONCLUSION: An assessment of transplant-related complications is important in improving the performance of HSCT. The present data suggest that a special therapeutic strategy is necessary for HSCT using low-frequency HLA haplotypes.

A case of thrombotic thrombocytopenic purpura induced by acute pancreatitis.

Thrombotic thrombocytopenic purpura (TTP) is a multisystemic microvascular disorder that may be caused by an imbalance between unusually large von Willebrand factor multimers and the cleaving protease ADAMTS13. In acquired TTP, especially in secondary TTP with various underlying diseases, the diagnosis is difficult because there are many cases that do not exhibit severe deficiency of ADAMTS13 or raised levels of ADAMST13 inhibitors. It is well known that collagen disease, malignancy, and hematopoietic stem cell transplantation can be underlying conditions that induce TTP. However, TTP induced by acute pancreatitis, as experienced by our patient, has rarely been reported. Our patient completely recovered with treatments using steroids and plasma exchange (PE) only. In cases where patients develop acute pancreatitis with no apparent causes for hemolytic anemia and thrombocytopenia, the possibility of TTP should be considered. Treatments for TTP including PE should be evaluated as soon as a diagnosis is made.

Impact of fresh frozen plasma on hepatectomy for hepatocellular carcinoma.

BACKGROUND: Little is known about the effect of transfusing fresh frozen plasma on the outcome after hepatectomy for hepatocellular carcinoma. PATIENTS AND METHODS: Among 410 patients who underwent curative resection between 1992 and 2005, 180 patients had perioperative transfusion with whole blood or packed red blood cells and fresh frozen plasma (group A), while 46 patients were only transfused with packed red cells (group B), 43 patients were only transfused with fresh frozen plasma (group C) and 141 patients had no transfusion (group D). RESULTS: Group C had significantly fewer postoperative complications and a shorter hospital stay than group A. Preoperative coagulation was significantly worse in group C. Survival was significantly better in groups C and D than in group A. CONCLUSION: Perioperative transfusion of fresh frozen plasma improves clotting factors without an adverse influence on the survival of patients with liver dysfunction undergoing resection of hepatocellular carcinoma.