A 46-Year-Old Thai Woman with Secondary Acquired Pure Red Cell Aplasia Due to Treatment with Recombinant Erythropoietin While on Dialysis for End-Stage Renal Disease Who Recovered Following ABO-Incompatible Kidney Transplantation.

BACKGROUND Pure red cell aplasia (PRCA) is an uncommon cause of anemia in end-stage kidney disease (ESKD). It is attributed to recombinant human erythropoietin (rHuEPO) administration. Although immunosuppression is the mainstay therapy, its effectiveness varies from 30% to 70%. PRCA in ESKD has been reported to improve following kidney transplantation. CASE REPORT A 46-year-old woman with ESKD secondary to lupus nephritis was treated for uremia at our center. She developed severe anemia. Bone marrow aspiration and biopsy revealed a reduction of erythroid precursors, consistent with PRCA. Because she had no sibling's blood group matched with her, ABO-incompatible kidney transplantation was an option for treatment. She underwent a desensitization protocol consisting of rituximab 375 mg/m2, tacrolimus, mycophenolate mofetil, and prednisolone 4 weeks before surgery, in addition to 3 sessions of double-filtration plasmapheresis (DFPP) every other day followed by intravenous immunoglobulin (IVIG) and 1 session of specific immunoadsorption (Glycosorb® B column) at pre-transplant day -1. She also received low-dose rabbit anti-thymocyte globulin (rATG) (Thymoglobulin®) (total 2.0 mg/kg). Maintenance therapy included tacrolimus, mycophenolate mofetil, and prednisolone. Allograft function normalized a few days after transplantation and her Hb gradually increased. CONCLUSIONS We report a rare case of PRCA in a patient with ESKD undergoing ABO-incompatible kidney transplantation. The outcome was satisfactory, with complete correction of anemia and kidney function.

Detection of dengue, chikungunya, and Zika RNA in blood donors from Southeast Asia.

BACKGROUND: Chikungunya (CHIKV), dengue (DENV), and Zika (ZIKV) viruses are of concern due to the potential of transfusion transmission in blood, especially in regions such as Southeast Asia where the viruses are endemic. The recent availability of nucleic acid testing (NAT) to screen blood donations on an automated platform provides the opportunity to detect potentially infectious units in asymptomatic donors. STUDY DESIGN AND METHODS: Three thousand blood donations from Vietnam and 6000 from Thailand were screened with a real-time polymerase chain reaction (PCR) test (cobas CHIKV/DENV, Roche Diagnostics, Indianapolis, IN) and equal numbers on cobas Zika (Roche Diagnostics). Reactive samples were tested by alternative NAT with resolution of discordant results by heminested PCR. Throughput of simultaneous testing of the two assays on the cobas 8800 system (Roche Diagnostics) was evaluated. RESULTS: In Vietnam, 9 of 3045 samples were reactive for DENV and all were confirmed, for a prevalence (with 95% confidence interval [CI]) of 0.296% (0.135-0.560). In Thailand, 2 of 6000 samples were reactive for CHIKV, 4 of 6000 for DENV, and 1 of 6005 for ZIKV, and all confirmed. The prevalence of CHIKV is 0.033% (0.004-0.120), DENV 0.067% (0.018-0.171), and ZIKV 0.017% (0.000-0.093). The overall specificity for the cobas CHIKV/DENV and cobas Zika tests was 100% (99.959-100). For the simultaneous assay testing, 960 test results were available in 7 hours and 53 minutes. CONCLUSION: Detection of CHIKV, DENV, and ZIKV RNA in donor samples in Vietnam and Thailand indicate the presence of the virus in asymptomatic blood donors. The cobas 6800/8800 systems (Roche Molecular Systems, Pleasanton, CA) enable screening blood donations in endemic areas for these viruses together or separately.

Genetic profiles of killer-cell immunoglobulin-like receptors and HLA ligands in Thai blood donors.

Killer-cell immunoglobulin-like receptors (KIRs) play an important role in natural killer (NK) cell regulation. Interaction of KIRs with human leukocyte antigen (HLA) class I molecules can transmit signals to regulate the function of NK cells. In this study, the diversities of KIR genes and their ligands in 500 Thai blood donors were investigated. The coexistence of inhibitory KIRs (iKIR), activating KIRs (aKIR) and their ligands in the same individuals were also analyzed. Overall, 36 KIR genotypes were identified. The most common genotype was genotype AA1 (40.8%). All individuals carried at least one iKIR-HLA pair whereas 18% of the individuals lacked aKIR-HLA pair. The most common compound KIR-HLA profile was the presence of 3 iKIR-HLA pairs with 1 aKIR-HLA pair (21.4%). The most common compound gene profile of KIR-HLA pairs was the combined presence of KIR2DL3-C1, 3DL1-Bw4, 3DL2-A3/A11 and the full length KIR2DS4-its ligands (8%). This study provided a comprehensive analysis of the KIR-HLA profiles in Thai blood donors in regards to KIR genotypes, HLA ligands, KIR-HLA ligand pairs and compound gene profiles of both iKIRs and aKIRs and their ligands. These findings will be useful as baseline information for further studies in the associations of KIR genes and various diseases.

Dengue infection in hematologic-oncologic pediatric patients: aggravation of anemia and bleeding risk.

We studied anemia and bleeding risk among hematologic-oncologic pediatric patients with dengue infection. A total of 907 patients suspected of having dengue infection were included in the study. They were categorized into 2 groups: 1) patients with confirmed dengue infection (n=843) and 2) patients with other febrile illnesses (n = 64). Both groups included patients with underlying hematologic-oncologic diseases (55 vs 14) and without underlying disease (788 vs 50). Patients with underlying diseases were divided into 3 subgroups by risk: Subgroup A, anemia risk, including patients with thalassemia and hemoglobinopathies (n = 39) and G6PD deficiency (n=6); Subgroup B, patients with bleeding risk, including hemophilia (n = 7), von Willebrand disease (n = 1) and thrombocytopenia (n = 4); and Subgroup C, patients with anemia and bleeding risk, including oncologic diseases (n =12). Acute hemolysis in Subgroup A started during the febrile stage and required packed red cell transfusions. Bleeding risk in Subgroup B started during the early febrile stage with vasculopathy and continued to the late febrile stage with thrombocytopenia. These patients required factor concentrate and platelet concentrate transfusions. Anemia and bleeding risk in Subgroup C was greater among patients undergoing chemotherapy than those who had discontinued treatment. The greater the length of time since discontinuation of treatment, the lower risk. The case-fatality rate among dengue infected patients with underlying disease (2/55 = 3.64%) was significantly higher than those without underlying disease 0.63% (5/788).

Occult hepatitis B virus infection in Thai blood donors.

BACKGROUND: An evaluation by the National Blood Center, the Thai Red Cross Society, of two commercial multiplex nucleic acid tests (NATs; the Chiron PROCLEIX ULTRIO test and the Roche Cobas TaqScreen MPX test) for screening Thai blood donors for hepatitis B virus (HBV), hepatitis C virus, and human immunodeficiency virus Type 1 identified 175 HBV NAT-reactive/hepatitis B surface antigen (HBsAg)-negative donors. The classification of the HBV infection of these donors was confirmed by follow-up testing. STUDY DESIGN AND METHODS: Index samples were tested for HBV serologic markers and HBV viral loads were determined. Donors were followed for up to 13 months and samples were tested with both NAT assays and for all HBV serological markers. RESULTS: Of 175 HBV NAT-yield donors, 72 (41%) were followed. Based on the follow-up results, the majority of donors who were followed had an occult HBV infection (66.7%), followed by donors with a primary, acute infection (26.4%). The majority of donors in this latter group (20.8%) were in the window period. Three donors (4.2%), who were anti-HBs positive, had a reinfection or breakthrough infection. CONCLUSION: The majority of donors detected during routine screening, who were HBsAg negative and NAT reactive, had an occult HBV infection, thus validating the decision to introduce NAT for blood donations in Thailand.

Genetic polymorphisms and haplotypes of DNA repair genes in childhood acute lymphoblastic leukemia.

BACKGROUND: Polymorphisms of DNA repair genes can alter protein structure and may impair DNA repair capacity. Defects in repairing damaged DNA lead to genetic instability and carcinogenesis. This study was performed to evaluate the effect of the polymorphisms of DNA repair genes on risk of childhood acute lymphoblastic leukemia (ALL). PROCEDURES: We genotyped polymorphisms of X-ray repair cross-complimenting group 1 (XRCC1) codon 194 (Arg to Trp), 280 (Arg to His) and 399 (Arg to Gln), and xeroderma pigmentosum group D (XPD) codon 312 (Asp to Asn) and 715 (Lys to Gln) in 108 children with ALL and 317 healthy controls using PCR-RFLP method. The allele, genotype, and haplotype frequencies of these polymorphisms were compared between cases and controls using Chi-square or Fisher's exact test. PHASE computer software was used to analyze estimated haplotypes of the XRCC1 and XPD polymorphisms. RESULTS: The frequency of XRCC1 194Trp allele in patients was significantly lower than that in controls (odds ratio (OR) 0.67; 95% confidence interval (CI), 0.47-0.97). Individuals with XRCC1 194 Trp/Trp genotype had a significantly reduced risk of ALL (OR 0.22; 95% CI, 0.05-0.96). The frequency of the XRCC1 haplotype B (194Trp-280Arg-399Arg) was significantly lower in children with ALL when compared to controls. The XRCC1 399Gln allele was associated with a significantly increased risk of ALL (OR 1.67; 95% CI, 1.20-2.33). The frequency of the XRCC1 haplotype C (194Arg-280Arg-399Gln) was significantly higher in patients. There was no difference of allele frequencies of the XRCC1 280 (Arg to His), XPD 312 (Asp to Asn), or XPD 715 (Lys to Gln) between cases and controls. CONCLUSION: The XRCC1 194Trp allele and haplotype B showed a protective effect against development of childhood ALL. In contrast, individuals with the XRCC1 399Gln allele and haplotype C were associated with increased risk for this disease.