International review of blood donation screening for anti-HBc and occult hepatitis B virus infection.

BACKGROUND: Hepatitis B core antibody (anti-HBc) screening has been implemented in many blood establishments to help prevent transmission of hepatitis B virus (HBV), including from donors with occult HBV infection (OBI). We review HBV screening algorithms across blood establishments globally and their potential effectiveness in reducing transmission risk. MATERIALS AND METHODS: A questionnaire on HBV screening and follow-up strategies was distributed to members of the International Society of Blood Transfusion working party on transfusion-transmitted infectious diseases. Screening data from 2022 were assimilated and analyzed. RESULTS: A total of 30 unique responses were received from 25 countries. Sixteen respondents screened all donations for anti-HBc, with 14 also screening all donations for HBV DNA. Anti-HBc prevalence was 0.42% in all blood donors and 1.19% in new donors in low-endemic countries; however, only 44% of respondents performed additional anti-HBc testing to exclude false reactivity. 0.68% of anti-HBc positive, HBsAg-negative donors had detectable HBV DNA. Ten respondents did universal HBV DNA screening without anti-HBc, whereas four respondents did not screen for either. Deferral strategies for anti-HBc positive donors were highly variable. One transfusion-transmission from an anti-HBc negative donor was reported. DISCUSSION: Anti-HBc screening identifies donors with OBI but also results in the unnecessary deferral of a significant number of donors with resolved HBV infection and donors with false-reactive anti-HBc results. Whilst confirmation of anti-HBc results could be improved to reduce donor deferral, transmission risks associated with anti-HBc negative OBI donors must be considered. In high-endemic areas, highly sensitive HBV DNA testing is required to identify infectious donors.

International review of blood donation nucleic acid amplification testing.

BACKGROUND AND OBJECTIVES: Nucleic acid amplification testing (NAT), in blood services context, is used for the detection of viral and parasite nucleic acids to reduce transfusion-transmitted infections. This project reviewed NAT for screening blood donations globally. MATERIALS AND METHODS: A survey on NAT usage, developed by the International Society of Blood Transfusion Working Party on Transfusion-transmitted Infectious Diseases (ISBT WP-TTID), was distributed through ISBT WP-TTID members. Data were analysed using descriptive statistics. RESULTS: Forty-three responses were received from 32 countries. Increased adoption of blood donation viral screening by NAT was observed over the past decade. NAT-positive donations were detected for all viruses tested in 2019 (proportion of donations positive by NAT were 0.0099% for human immunodeficiency virus [HIV], 0.0063% for hepatitis C virus [HCV], 0.0247% for hepatitis B virus [HBV], 0.0323% for hepatitis E virus [HEV], 0.0014% for West Nile virus [WNV] and 0.00005% for Zika virus [ZIKV]). Globally, over 3100 NAT-positive donations were identified as NAT yield or solely by NAT in 2019 and over 22,000 since the introduction of NAT, with HBV accounting for over half. NAT-positivity rate was higher in first-time donors for all viruses tested except WNV. During 2019, a small number of participants performed NAT for parasites (Trypanosoma cruzi, Babesia spp., Plasmodium spp.). CONCLUSION: This survey captures current use of blood donation NAT globally. There has been increased NAT usage over the last decade. It is clear that NAT contributes to improving blood transfusion safety globally; however, there is a need to overcome economic barriers for regions/countries not performing NAT.

An international review of the characteristics of viral nucleic acid-amplification testing (NAT) reveals a trend towards the use of smaller pool sizes and individual donation NAT.

BACKGROUND AND OBJECTIVES: Nucleic acid-amplification testing (NAT) is used for screening blood donations/donors for blood-borne viruses. We reviewed global viral NAT characteristics and NAT-yield confirmatory testing used by blood operators. MATERIALS AND METHODS: NAT characteristics and NAT-yield confirmatory testing used during 2019 was surveyed internationally by the International Society of Blood Transfusion Working Party Transfusion-Transmitted Infectious Diseases. Reported characteristics are presented herein. RESULTS: NAT was mainly performed under government mandate. Human immunodeficiency virus (HIV), hepatitis C virus (HCV) and hepatitis B virus (HBV) NAT was performed on all donors and donation types, while selective testing was reported for West Nile virus, hepatitis E virus (HEV), and Zika virus. Individual donation NAT was used for HIV, HCV and HBV by ~50% of responders, while HEV was screened in mini-pools by 83% of responders performing HEV NAT. Confirmatory testing for NAT-yield samples was generally performed by NAT on a sample from the same donation or by NAT and serology on samples from the same donation and a follow-up sample. CONCLUSION: In the last decade, there has been a trend towards use of smaller pool sizes or individual donation NAT. We captured characteristics of NAT internationally in 2019 and provide insights into confirmatory testing approaches used for NAT-yields, potentially benefitting blood operators seeking to implement NAT.

Anti-HBc-nonreactive occult hepatitis B infections with HBV genotypes B and C in vaccinated immunocompetent adults.

Absence of anti-HBc reactivity with detectable anti-HBs was observed in blood donors with occult hepatitis B virus (HBV) infection (OBI). The prevalence and mechanisms underlying this uncommon condition were investigated over time in Chinese blood donors with OBI. Isolated anti-HBs OBI status was identified from 466,911 donors from Dalian, China, and monitored in follow-up (range: 2.6-84.3 months). HBV vaccination status was documented, and infecting viral strains were characterized. Of 451 confirmed OBIs (1:1035), 43 (9.5%; 1:10,858) had isolated anti-HBs as only serological marker. Isolated anti-HBs OBIs differed from anti-HBc-reactive OBIs by significantly younger age (median 24 years), higher HBV DNA (median: 20 IU/ml) and anti-HBs (median 60.5 IU/L) levels, paucity of mutations in HBV Core and S proteins, and high vaccination rate (72%). Vaccinated isolated anti-HBs OBIs (n = 31) differed from unvaccinated (n = 11) by significantly younger age (22 vs 38 years), higher anti-HBs level at index (48% vs 9% with anti-HBs >100 IU/L) and higher frequency of anti-HBs immune response (44% vs 20%). Of 15 vaccinated and 5 unvaccinated OBIs follow-up, 65% (8 vaccinated and 5 unvaccinated) became HBV DNA negative suggesting aborted recent infection, while 35% (7 vaccinated) had low persistent viraemia 2 to 65 months post index. In conclusion, isolated anti-HBs OBI in Chinese blood donors appears associated with young, vaccinated, adults exposed to HBV who predominantly develop low level aborted infection revealed by transient HBV DNA and immune anti-HBs response. However, a subset of individuals still experienced low but persistent viral replication whose clinical outcome remains uncertain.

Follow-up program for blood donors with unconfirmed screening results reveals a high false-positive rate in Dalian, China.

BACKGROUND: Chinese blood donors with unconfirmed serological and/or molecular screening results are deferred permanently. This study investigated the implementation and performance of a follow-up program aiming to improve the notification and management of deferred donors in Dalian, China. STUDY DESIGN AND METHODS: From January 2013 to February 2018, 411,216 donations were tested for HBsAg, anti-HCV, anti-HIV/HIV antigen, and antibodies to Treponema pallidum. HBV, HCV, and HIV nucleic acid testing (NAT) was performed in mini-pools of six or in individual donations (IDs). Reactive donations were evaluated further with alternative serological assays and ID-NAT re-testing. A follow-up procedure was developed to evaluate a subset of deferred donors that were either potential NAT yield cases, serology non-reactive and NAT non-repeated reactive (NRR), or serology NRR irrespective of NAT result. RESULTS: Serological and molecular routine, plus supplemental testing, identified HBV, HCV, HIV, and TP in 503 (0.12%), 392 (0.09%), 156 (0.04%), and 2041 (0.49%) donations, respectively. Overall, 683 of 4156 (16.4%) eligible donors and 205 donors deferred prior 2013 participated in the program. They included 664 serology NRR and 224 NAT yield cases, and 58.8% repeat donors. All markers combined, follow-up documented false reactivity, primary acute infections, and OBI in 61.9% (550/888), 3.3% (29/888), and 12.8% (114/888) of these donors, respectively. Isolated anti-HBc or anti-HBs reactivity was observed in 22% of cases. CONCLUSION: Follow-up testing refined infection status in 78.0% (693/888) of deferred donors with unconfirmed screening results. This high false-positive rate encouraged to reevaluate the current screening strategies and to consider donor reentry.

Blood cell parameters for screening and diagnosis of hereditary spherocytosis.

BACKGROUND: There is currently no single index for the diagnostic screening of hereditary spherocytosis (HS). However, hematology analyzers are widely used in hospital laboratories because of their highly automated performance and quality control procedure, and detection of some blood cell parameters may be useful for the early screening of HS. METHODS: We investigated the values of blood cell parameters for the screening and differential diagnosis of HS. We performed a descriptive study of 482 samples (67 cases of HS, 59 cases of G6PD deficiency, 57 cases of AIHA, 199 cases of thalassemia, and 100 cases of healthy controls) that were run on Beckman Coulter LH780 Hematology Analyzer. RESULTS: HS was characterized by increased MCHC, decreased MRV, MSCV-MCV < 0, and increased Ret with no concomitant increase in IRF. The areas under the ROC curves were MSCV-MCV (0.97; 95% CI 0.95-1.0) > MRV (0.94; 95% CI 0.91-0.97) > MCHC (0.92; 95% CI 0.88-0.97) > Ret/IRF (0.77; 95% CI 0.7-0.84). MSCV-MCV ≤ 0.6 fl was valuable parameter for the diagnostic screening of HS, with a sensitivity of 95.5% and specificity of 94.9%. CONCLUSION: These indices have high reference values for differentiating HS from thalassemia, AIHA, and G6PD deficiency.

Abnormal fibrinogen with an Aα 16Arg → Cys substitution is associated with multiple cerebral infarctions.

We found a heterozygous dysfibrinogenemia caused by a substitution of AαArg16Cys. The proband suffered multiple cerebral infarctions. Routine coagulation tests revealed a prolonged thrombin time. The fibrinogen levels in the functional assays were considerably lower than the levels in the immunological assays. The polymerization of the purified fibrinogen was strongly impaired in the presence of calcium. As previously observed in other heterozygous Aα R16C variants, the release rate and amount of fibrinopeptide A (FPA) were lower in the proband than those in normal controls. Additionally, the release of fibrinopeptide B (FpB) was delayed. The immunoblotting analysis using antibodies against human serum albumin indicated that albumin is bound to Aα R16C. The mass spectrometry analysis showed that the Aα R16C fibrinogen chains appeared in the patient's circulation. The clot structure analysis using scanning electron microscopy (SEM) revealed that the fibrin network was dense and consisted of thin and highly branched fibres. Using overlaid fibrinolytic enzymes in a clot lysis experiment, clot degradation was observed to be delayed. These results indicated that the thrombotic tendency may be ascribed to a fibrinolytic resistance caused by an abnormal clot structure with thin fibres and fibrinogen-albumin complexes.

Combined use of Clauss and prothrombin time-derived methods for determining fibrinogen concentrations: Screening for congenital dysfibrinogenemia.

BACKGROUND: In this study, the significance of fibrinogen concentration assessed by a combination of Clauss and prothrombin time (PT)-derived methods for screening for congenital dysfibrinogenemia were investigated, and the screening efficiency of fibrinogen PT-derived/Clauss ratio on congenital dysfibrinogenemia was analyzed. METHODS: We compared fibrinogen concentrations determined by the Clauss, PT-derived, and enzyme-linked immunosorbent assay (ELISA) methods in 73 patients with congenital dysfibrinogenemia and 81 normal controls. Receiver operating characteristic (ROC) curves were utilized to evaluate the efficacy of fibrinogen PT-derived/Clauss ratio in screening for congenital dysfibrinogenemia. RESULTS: Fibrinogen concentrations determined by the Clauss method were dramatically lower than by the PT-derived method and ELISA, and correlated poorly with the latter two methods in patients with congenital dysfibrinogenemia. Fibrinogen concentrations in normal controls were slightly lower according to the Clauss method than to the PT-derived method and ELISA; however, each method yielded results within the normal range and the correlation was good. The area under the ROC curve of fibrinogen PT-derived/Clauss ratio for diagnosis of congenital dysfibrinogenemia was 1 with a standard error of 0, 95% confidence interval of 0.976-1.00, and optimal critical diagnosis point of 1.43. When fibrinogen PT-derived/Clauss ratio was >1.43, the sensitivity and specificity for diagnosis of congenital dysfibrinogenemia were both 100%. CONCLUSIONS: The combined use of Clauss and PT-derived methods for determining fibrinogen concentrations improves the efficiency of screening for congenital dysfibrinogenemia, as the fibrinogen PT-derived/Clauss ratio has high sensitivity and specificity in diagnosis of congenital dysfibrinogenemia. This ratio could serve an important screening tool for this disease.

Evaluation of a Flow-Cytometric Osmotic Fragility Test for Hereditary Spherocytosis in Chinese Patients.

BACKGROUND: Osmotic fragility testing based on flow cytometry was recently introduced for the screening of hereditary spherocytosis (HS). This study was undertaken to evaluate the clinical diagnostic value of a flow-cytometric osmotic fragility test for HS. METHODS: Peripheral blood was collected from 237 subjects at the First Affiliated Hospital of Guangxi Medical University, including 56 HS patients, 86 thalassemia patients and 95 healthy controls. The samples were examined by flow-cytometric osmotic fragility test and the percentage of residual red blood cells was used to determine HS. Peripheral blood smears were performed to examine the red blood cell morphology. RESULTS: With clinical diagnosis of HS as the gold standard and the percentage of residual red blood cells <23.6% as the diagnostic threshold in the flow-cytometric osmotic fragility test, the sensitivity of the flow-cytometric osmotic fragility test for HS was 85.71% and the specificity was 97.24%. CONCLUSION: The flow-cytometric osmotic fragility test combined with a red blood cell morphology test by peripheral blood smear could be a simple, practical and accurate laboratory screening method for HS.

[Analysis of a family with congenital dysfibrinogenemia caused by an Arg275His mutation in the gamma chain of fibrinogen].

OBJECTIVE: To explore the clinical phenotype of a family affected with congenital dysfibrinogenemia and potential mutations underlying the disease. METHODS: Coagulation testing and hepatorenal function testing were conducted on 18 individuals from three generations. Plasma fibrinogen was extracted and analyzed with SDS-PAGE electrophoresis. All of the exons and flanking sequences of fibrinogen FGA, FGB, FGG genes were analyzed by PCR, and the products were subjected to Sanger sequencing. RESULTS: Hepatorenal function, prothrombin time and activated partial thromboplastin time of the proband were all normal. However, his thrombin time was significantly prolonged. Fibrinogen activity was decreased, while the concentration of antigen was in the normal range. The results of his mother, brother, and nephew were similar. DNA sequencing has confirmed that the proband, his mother, brother, and nephew have all carried a g.5877G>A mutation in the exon 8 of the FGG gene, which resulted in replacement of arginine (Arg) by histidine (His) at position 275. CONCLUSION: The Arg275His mutation of the fibrinogen gamma chain probably underlies the pathogenesis of congenital dysfibrinogenemia in this family.

No Hepatitis Delta Virus Seropositivity among Blood Donors with Overt and Occult Hepatitis B Infection in Dalian, Liaoning Province, China.

Hepatitis delta virus (HDV) is an obligate satellite of hepatitis B virus (HBV). Dual HDV/HBV infection is associated with down-regulated HBV replication and fast progression to severe liver disease. Although HDV is transmissible through exposure to infected blood, data about HDV infection in blood donors remain scarce. Between 2011 and 2021, 869,633 donations were collected from prequalified donors in Dalian, China. In total, 1060 (0.12%) were confirmed HBsAg and/or HBV DNA-reactive. Subsequently, anti-HDV IgG was tested in 2175 donations, including 65 that tested HBsAg+ pre donation, 1017 confirmed HBV-positive (507 HBsAg+/HBV DNA+, 33 HBsAg+/DNA-, 477 HBsAg-/DNA+ (451 occult (OBI) and 26 acute infections)), 327 viral DNA non-repeated-reactive, 397 anti-HBc-only, and 369 anti-HBs-only. Two (0.09%) samples tested anti-HDV IgG weakly reactive but were unconfirmed by IgM and IgG repeat testing with alternative assays, suggesting an initial false reactivity. In addition, HDV testing in a subgroup of confirmed OBI donors, comprising 451 donors from Dalian and 126 archived samples of OBI donors from around the world, showed only one non-Chinese donor to be repeatedly anti-HDV-reactive, suggesting that HDV/HBV coinfection does not play a significant role in the genesis of OBI. The overall data suggested an extremely low prevalence of HDV infection among blood donors in Liaoning province, Northeast China.

[Magnetic activated cell sorting and its application in the studies of male infertility].

Magnetic activated cell sorting (MACS) is considered as a flexible, fast, specific and simple cell sorting system that can separate target cells effectively according to specific markers on the cell surface, for which it has won a wide clinical application. MACS offers a new platform for male infertility research, as well as a novel idea for applying this technology in the optimization of semen quality and the isolation of germ cells. This article briefly introduces the basic principles of MACS, and summaries its present and potential clinical application in male infertility research, as in spermatozoa selection and cryopreservation, and the isolation of spermatogonial stem cells and germ cells.

Re-Entry Evaluation of Chinese Blood Donors with Unconfirmed Hepatitis B Screening Results.

The hepatitis B virus (HBV) remains a high priority for Chinese blood banks due to the high prevalence of infection. HBV blood safety has been significantly improved by the implementation of highly sensitive and specific serological and molecular HBV screening assays. The multiplication of viral markers tested and the ever-increasing analytical sensitivity of the tests can make the interpretation of the results difficult. False-positive or indeterminate results may lead to permanent donor deferrals and conflicts between donors and blood banks. To avoid blood shortages, blood services aim to limit unnecessary donor losses by developing procedures for the re-entry of donors temporarily deferred due to an unconfirmed HBV reactivity. The development of such procedures based on donor follow-up and HBV confirmation remains limited. A review of the scarce data available revealed considerable heterogeneity in testing methods and re-entry algorithms, limited validation studies, and a lack of accurate assessment of the residual infectious risk potentially associated with donor re-entry. In conclusion, systematic and widely validated confirmatory testing and prolonged follow-up are essential for safe re-entry of temporary deferred donors. Standardization of HBV testing methods and the establishment of dedicated expert laboratories are needed because of the complexity of HBV infection in blood donors.

[Genetic Analysis and Prenatal Diagnosis of a Family with Hereditary Spherocytosis Caused by a Novel Compound Heterozygous Mutation of SPTB Gene].

OBJECTIVE: To investigate the clinical and genetic characteristics of a family with hereditary spherocytosis (HS), to clarify the cause of the disease, and to provide the basis for genetic counseling and prenatal diagnosis. METHODS: The clinical data of proband and his parents were collected, and HS-related pathogenic genovariation of the proband was detected by high throughput sequencing. Suspected pathogenic mutation sites were verified by PCR-Sanger sequencing, and the fetus were conceived by a proband mother underwent prenatal diagnosis. RESULTS: Clinical manifestations of the proband showed moderate anemia, mild splenomegaly, and jaundice (an indirect increase of bilirubin). The gene detection showed that the proband showed compound heterozygous mutations of SPTB gene c. 6095T > C (p.Leu2032Pro) and c. 6224A > G (p.Glu2075Gly), which was inherited from the asymptomatic mother and father, respectively. Both mutations were detected rarely in the common population. Prenatal diagnosis revealed that the fetus inherited a mutant gene of the mother. CONCLUSION: The compound heterozygous mutations of SPTB genes c.6095T>C (p.Leu2032Pro) and c.6224A>G (p.Glu2075Gly) were the causes of the family disease, which provides a basis for family genetic counseling and prenatal diagnosis. This report is the first one found in the HGMD,1000G and EXAC database, which provides an addition to the mutation profile of the SPTB gene.

Alternative hepatitis B virus DNA confirmatory algorithm identified occult hepatitis B virus infection in Chinese blood donors with non-discriminatory nucleic acid testing.

BACKGROUND: Multiplex viral nucleic acid testing (NAT) and a discriminatory testing algorithm have been used to detect viral infections in blood donors. Non-discriminated reactive (NDR) results may arise from low hepatitis B virus (HBV) DNA levels and are challenging for donor management by blood services. The aim of this study was to evaluate the performance and feasibility of alternative viral particle concentration methods to confirm and to characterise HBV infection status in NDR donors from Dalian, China, in order to improve routine donor management according to the potential residual risk estimate. MATERIALS AND METHODS: Individual donations were tested with ULTRIO Plus, and discriminated when reactive. Virions were concentrated from 12 and 6 mL plasma samples by ultracentrifugation (UC) and polyethylene glycol (PEG) precipitation, respectively. HBV DNA was detected with four nested polymerase chain reactions (95% limit of detection: 5-25 IU/mL). Amplified products were sequenced for definitive confirmation. Anti-HBc and anti-HBs were tested. RESULTS: Of 77,556 donors, 79 (0.1%) were NAT NDR. After viral particle concentration by UC and PEG precipitation, HBV DNA was detected in 46 (58.2%) and 34 (43.0%) NDR donors, respectively, including 61.7% of samples that were repeatedly non-reactive with multiple NAT testing. Anti-HBc and anti-HBs (median titre: 37 mIU/mL) were detected in 87.3% and 46.8% of NDR donors, respectively. Sequencing confirmed HBV DNA in 65.8% of NDR donors, of whom 96.2% were occult HBV carriers with rare mutations in S and core proteins. DISCUSSION: A HBV DNA confirmatory procedure with limited technical constraints was implemented successfully. The majority of NDR donors had occult HBV infections with extremely low viral DNA levels, which may constitute a potential residual threat for blood safety. Only a minority of anti-HBc+ NDR donors had anti-HBs levels high enough to consider their reinstatement as donors. The data support the permanent deferral of NDR donors to ensure maximum blood safety in areas of high HBV endemicity.

Potential Role of Hypothalamic and Plasma Ghrelin in the Feeding Behavior of Obese Type 2 Diabetic Rats with Intraventricular Glucagon-Like Peptide-1 Receptor Agonist Intervention.

OBJECTIVE: To investigate the relationship of central and peripheral ghrelin during an exendin-4 (Ex-4) intervention to feeding in obese type 2 diabetic rodents. METHODS: Animal models of diet-induced obesity (DIO) and type 2 diabetes were developed using male Sprague-Dawley rats fed with a high-fat diet and induced into DIO-streptozotocin diabetic rats. Ex-4 or the glucagon-like peptide-1 (GLP-1) receptor agonist exendin fragment-[9-39] (Ex-9) was intracerebroventricularly (ICV) administered. Multivariate linear regression analysis was performed to investigate potential predictors of food intake after Ex-4 administration. RESULTS: ICV administration of Ex-4 significantly inhibited feeding and decreased weight, plasma active ghrelin, hypothalamic ghrelin, and gastric ghrelin levels. The changes in hypothalamic ghrelin and plasma ghrelin could predict the amount of 8-h average food intake. Central preadministration of Ex-9 followed by treatment with Ex-4 could inhibit the decrease in feeding at 0.5, 2, and 8 h. It could also inhibit the decrease in hypothalamic ghrelin at 0.5, 2, and 8 h, as well as in plasma and gastric ghrelin at 2 and 8 h. CONCLUSIONS: In a GLP-1 receptor-dependent manner, central and peripheral ghrelin play a vital role in the inhibition of feeding by Ex-4 administration. Hypothalamic ghrelin, but not plasma ghrelin, may be involved in central Ex-4 inhibition of feeding in the very early feeding period.

Hereditary spherocytosis overlooked for 7 years in a pediatric patient with ß-thalassemia trait and novel compound heterozygous mutations of SPTA1 gene.

Objectives: We aimed to determine the clinical and genetic characteristics of a boy diagnosed with the ß-thalassemia trait. He also had hereditary spherocytosis (HS) that had been overlooked for 7 years. Methods: Blood samples collected from the proband and his family were assessed by laboratory tests, and next-generation sequencing (NGS) and Sanger sequencing. Results: The ß-thalassemia trait was complicated with HS in the proband. Compound heterozygous mutations of the Spectrin Alpha, Erythrocytic 1 (SPTA1) gene, c.83G > A and c.190G > A in the proband were inherited from his mother and father, respectively, and he also had the heterozygous c.126_129delCTTT mutation in the Hemoglobin Subunit Beta (HBB) gene. The c.190G > A mutation has not yet been added to the Human Gene Mutation Database (HGMD®). The heterozygous HBB c.126_129delCTTT mutation was inherited from his mother, and his older brother also had this mutation. Conclusion: Compared with other patients with either HS or ß-thalassemia, this proband with both HS and the ß-thalassemia trait had very complicated laboratory findings, which resulted in HS being overlooked for 7 years. Genetic testing is invaluable for the differential diagnosis of hereditary anemias with overlapping clinical features.

Correlation between hypocalcemia and acute exacerbation of chronic obstructive pulmonary disease in the elderly.

Introduction: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is an important disease of hospitalized elderly patients, who often have electrolyte imbalances. This study was performed to analyze total serum calcium levels in elderly patients with AECOPD and identify the correlation between hypocalcemia and AECOPD. Methods: 153 elderly patients with AECOPD served as the observation group, and 115 healthy elderly people undergoing physical examinations served as the control group. Differences in the corrected serum calcium, albumin (ALB), and neutrophil/lymphocyte ratio (NLR) were analyzed between the observation and control groups before and after treatment. The incidence of hypocalcemia was compared among patients at different ages and with different pulmonary function classifications before treatment. The relationship between hypocalcemia and respiratory infection was analyzed. Differences in the pretreatment NLR, ALB, logarithm of the serum C-reactive protein level (LogCRP), and hospital stay were compared between patients with and without hypocalcemia. Results: The corrected serum calcium level (P < 0.001), NLR (P = 0.001) and albumin level (P < 0.001) were significantly different among the pretreatment group, post-treatment group, and control group. The serum calcium level, LogCRP, and NLR were significantly lower after than before treatment (P < 0.05). Significant differences in the incidence of hypocalcemia were found among patients of different ages (P = 0.002). The respiratory infection rate (P < 0.001), hospital stay (P < 0.001), NLR (P = 0.007), and LogCRP (P < 0.001) was higher in patients with than without hypocalcemia. However, the albumin level was lower in patients with than without hypocalcemia (P < 0.001). Conclusions: In elderly patients with AECOPD, hypocalcemia may be related to the disease progression, respiratory infection rate, and hospital stay of patients with AECOPD.

α-thalassaemia combined with hereditary spherocytosis in the same patient.

A family of four from the Guangxi Zhuang Autonomous Region of China, including a child with α-thalassaemia and hereditary spherocytosis (HS), underwent laboratory identification, and genetic analysis. After harvesting peripheral blood samples from the child patient and his family members, GAP-polymerase chain reaction (PCR) and reverse dot-blot tests were used to identify thalassaemia genotypes. After amplifying exons and the adjacent introns of solute carrier family 4 member 1 (Diego blood group) (SLC4A1), ankyrin 1, spectrin α erythrocytic 1, spectrin ß erythrocytic and erythrocyte membrane protein band 4.2 by PCR, DNA sequencing was utilised to detect gene mutations of HS. The thalassaemia gene of the child patient was -α3.7/αα and identical to the genotype of his mother. DNA testing of HS identified two mutation sites on the SLC4A1 gene: Exon 3 c.113A>C (Asp 38 Ala) and intron 7 c.609+86G>A. The father and older sister of the patient also had the same mutations. Due to the mutual interference with disorders of haemoglobin synthesis and erythrocyte membrane defects of laboratory results, it is difficult to diagnose HS when it coexists with thalassaemia. When clinical manifestations and laboratory results cannot be explained by a single haemolytic anaemia, the possibility of combining with another haemolytic anaemia should be considered. Thus, it is necessary to perform pedigree investigation and genetic analyses for a final diagnosis.