Screening and Diagnosis of Hb Quong Sze [HBA2: c.377T > C (or HBA1)] in a Prenatal Control Program for Thalassemia

Hb Quong Sze [Hb QS, HBA2: c.377T?>?C (or HBA1)] is a common nondeletional thalassemia in southern China. It is one of the major alleles causing nondeletional Hb H (β4) disease in the Chinese population. There is no strategy currently in place that aims to screen using hematological index cutoffs for this variant. This study was carried out to evaluate whether it is effective to use mean corpuscular hemoglobin (MCH) <27.0?pg as a screening test in the first step of screening for Hb QS carriers in southern China. The data of hematological testing in the Hb QS carriers obtained from couples who underwent prenatal thalassemia screening, regardless of the red blood cell (RBC) indices, were retrospectively reviewed. A total of 51 Hb QS carriers were identified, giving a prevalence rate of 0.2%; among these, 45 were Hb QS heterozygotes. The values of hemoglobin (Hb), MCV and mean corpuscular Hb (MCH) in the 45 Hb QS heterozygotes were 13.2?±?1.8?g/dL, 75.2?±?3.3?fL and 24.5?±?0.5?pg, respectively. Eight heterozygotes (17.8%) had an MCV value of >80.0?fL, ranging from 80.9 to 84.1?fL, and would not be detected using the cutoff value of MCV <80.0?fL as a criterion for thalassemia screening. However, if screening had been based on the MCH <27.0?pg value, all 45 Hb QS heterozygotes would have been detected. Using a cutoff value of MCH <27.0?pg in nondeletional thalassemia screening would greatly decrease the DNA diagnosis burden.     

Hb H Disease Results from Compound Heterozygosity of – –SEA and –αMAL3.5 in a Chinese Family

The α⁺-thal deletion of 3.557?kb (NG_000006.1: g.32745_36301del, –α^MAL3.5), involving the entire α2-globin gene, was identified in a Chinese family by multiplex ligation-dependent probe amplification (MLPA) followed by gap-polymerase chain reaction (gap-PCR) and sequencing. The proband, a compound heterozygote for this mutant gene and the Southeast Asian (–?–^SEA; NG_000006.1: g.26264_45564del19301) deletion, had a phenotype of Hb H disease [hemoglobin (Hb) 7.6?g/dL, mean corpuscular volume (MCV) 60.0 fL, Hb H (β4) 0.7%, Hb Bart’s (γ4) 2.4% and Hb A₂ 1.1%]; one of her sisters with same genotype showed a similar phenotype. Another two family members, who were carriers of this mutant gene, had a hematological phenotype of a silent α-thal. The 5' and 3' breakpoints of this deletion are located at the Y2 and Y1 boxes, respectively, therefore, it probably originated from an unequal crossover between these two homologous boxes. This mutation constitutes an additional heterogeneous defect causing α-thal in the Chinese population and would be valuable for elucidating the arrangement in the human α-globin gene cluster.     

Coexistence of Two β-Globin Gene Deletions in a Chinese Girl with β-Thalassemia Minor

This study reports a rare case of β^41/42,Cap/β^A genotype in a girl with β-thalassemia (β-thal) minor. The 13-month-old Chinese proband suffered anemia, diarrhea, stunted growth and emaciation. The routine polymerase chain reaction-reverse dot-blot (PCR-RDB) test result for β-thal mutations indicated that she was a compound heterozygote for β^41/42 and β^Cap. However, the complete blood cell (CBC) test gave the following results: mean corpuscular volume (MCV) 79.8 fL, mean corpuscular hemoglobin (MCH) 19.9?pg, with a Hb A₂ value of 5.66%, suggesting that the proband also was β-thal minor. The proband’s father showed typical microcytic hypochromic anemia characteristics with a decreased MCV and MCH (63.1 fL and 20.9?pg, respectively) and an increased level of Hb A₂ (5.60%), while the proband’s mother had normal levels of MCV, MCH and Hb A₂. The PCR-RDB test result showed her father was also a compound heterozygote for the β^41/42 (HBB: c.126_129delCTTT) and β^Cap (HBB: c.-11_-8delAAAC) mutations and her mother was normal. Finally, DNA sequencing identified that the β^41/42 and β^Cap mutations of the proband were inherited from her father and located on one β-globin gene, suggesting that the proband’s genotype is β^41/42,Cap/β^A.     

Prophylaxis of hepatic encephalopathy in acute variceal bleed: a randomized controlled trial of lactulose versus no lactulose

Background and Aims: Acute variceal bleed (AVB) is an important precipitating factor for development of hepatic encephalopathy (HE). However, there is paucity of data on the role of lactulose for prevention of HE after AVB. We evaluated the role of lactulose for prophylaxis of HE after AVB. Methods: Consecutive patients of cirrhosis with AVB enrolled. Patients included if >18 years old and had no HE at the time of presentation. Patients were randomized to receive lactulose (Group‐L) or no lactulose (Group‐P) along with standard treatment of AVB as per Baveno 4 guidelines. Primary endpoint was development of overt HE as per West Haven criteria within 120 h of randomization. Results: Seventy patients were randomized into group‐L (Gp‐L, n = 35) and group‐P (Gp‐P, n = 35). There was no significant difference in baseline characteristics between the two groups. Characteristics of variceal bleed were also similar (Gp‐L vs Gp‐P [mean arterial pressure 81.0 ± 10.5 vs 79.5 ± 9.9 mmHg], Hb [8.4 ± 1.5 vs 9.3 ± 2.3 g/dL], blood transfusion requirement [1.6 ± 1.1 vs 1.3 ± 0.9 units], time to endoscopy [6.3 ± 2.8 vs 7.0 ± 3.1 h], and esophageal source of bleed [92% vs 88%]). Nineteen (27%) patients developed HE; five patients (14%) in Gp‐L and 14 patients (40%) in Gp‐P, P = 0.03. The median grade of HE was 2 (range 2–4) and median time interval of development of HE after randomization was 2 days (range 1–4). Nine patients (13%) died; three (8.5%) patients in Gp‐L and six (17%) patients in Gp‐P, P = 0.23. Patients who developed HE had significantly higher baseline Child‐Turcotte‐Pugh score score (10.2 ± 1.2 vs 9.4 ± 1.4 P = 0.04), model for end stage liver disease score (18.2 ± 3.9 vs 15.4 ± 4.5 P = 0.02), arterial ammonia level (112.2 ± 22.7 vs 94.8 ± 17.6 umol/L, P = 0.001), baseline total leukocyte count (10 505.2 ± 8911.9 vs 5784.3 ± 3387.0 P = 0.002), total bilirubin (3.4 ± 1.3 vs 2.1 ± 1.8 mg%, P = 0.008) as compared to patients who did not develop HE. On multivariate analysis only baseline arterial ammonia, blood requirement during hospital stay and lactulose therapy were predictors of development of HE. Conclusions: Lactulose is effective in prevention of HE in patients with cirrhosis and acute variceal bleed.     

Coinfection with hepatitis C virus,oxidative stress and antioxidant status in HIV‐positive drug users in Miami*

Background

The pathogenesis of HIV/hepatitis C virus (HCV) coinfection is poorly understood. We examined markers of oxidative stress, plasma antioxidants and liver disease in HIV/HCV‐coinfected and HIV‐monoinfected adults.

Methods

Demographics, medical history, and proof of infection with HIV, hepatitis A virus (HAV), hepatitis B virus (HBV) and HCV were obtained. HIV viral load, CD4 cell count, complete blood count (CBC), complete metabolic panel, lipid profile, and plasma concentrations of zinc, selenium, and vitamins A and E were determined. Malondialdehyde (MDA) and glutathione peroxidase concentrations were obtained as measures of oxidative stress. Aminotransferase to platelet ratio index (APRI) and fibrosis index (FIB‐4) markers were calculated.

Results

Significant differences were found between HIV/HCV‐coinfected and HIV‐monoinfected participants in levels of alanine aminotransferase (ALT) (mean±standard deviation: 51.4±50.6 vs. 31.9±43.1 U/L, respectively; P=0.014), aspartate aminotransferase (AST) (56.2±40.9 vs. 34.4±30.2 U/L; P<0.001), APRI (0.52±0.37 vs. 0.255±0.145; P=0.0001), FIB‐4 (1.64±.0.91 vs. 1.03±0.11; P=0.0015) and plasma albumin (3.74±0.65 vs. 3.94±0.52 g/dL; P=0.038). There were no significant differences in CD4 cell count, HIV viral load or antiretroviral therapy (ART) between groups. Mean MDA was significantly higher (1.897±0.835 vs. 1.344± 0.223 nmol/mL, respectively; P=0.006) and plasma antioxidant concentrations were significantly lower [vitamin A, 39.5 ± 14.1 vs. 52.4±16.2 μg/dL, respectively (P=0.0004); vitamin E, 8.29±2.1 vs. 9.89±4.5 μg/mL (P=0.043); zinc, 0.61±0.14 vs. 0.67±0.15 mg/L (P=0.016)] in the HIV/HCV‐coinfected participants than in the HIV‐monoinfected participants, and these differences remained significant after adjusting for age, gender, CD4 cell count, HIV viral load, injecting drug use and race. There were no significant differences in glutathione peroxidase concentration, selenium concentration, body mass index (BMI), alcohol use or tobacco use between groups. Glutathione peroxidase concentration significantly increased as liver disease advanced, as measured by APRI (β=0.00118; P=0.0082) and FIB‐4 (β=0.0029; P=0.0177). Vitamin A concentration significantly decreased (β=?0.00581; P=0.0417) as APRI increased.

Conclusion

HIV/HCV coinfection is associated with increased oxidative stress and decreased plasma antioxidant concentrations compared with HIV monoinfection. Research is needed to determine whether antioxidant supplementation delays liver disease in HIV/HCV coinfection.

     

Comparison Between Capillary Electrophoresis and High Performance Liquid Chromatography for Detection and Quantification of Hb Constant Spring [Hb CS; α142, Term→Gln (TAA>CAA IN α2)]

Hb Constant Spring [Hb CS; α142, Term→Gln (TAA>CAA in α2)] is often missed by routine laboratory testing since its mRNA as well as gene product are unstable and presented at a low level in peripheral blood. This study aimed to analyze the efficacy of capillary electrophoresis (CE) and high performance liquid chromatography (HPLC) for detecting and quantifying Hb CS in 19 heterozygotes and 14 homozygotes with Hb CS as well as 10 Hb H-CS disease subjects who were detected by molecular analysis. In the CE electrophoregram, Hb CS was seen at zone 2 and was observed in all samples, while the chromatogram of Hb CS peaks was found in 26.32% heterozygotes, 42.86% homozygotes and 90% Hb H-CS disease subjects, respectively. In addition, the Hb CS levels in each group of subjects quantified by CE were significantly higher than those quantified by HPLC. Based on the CE method, the lowest Hb CS level was found in the heterozygotes, whereas the highest level was found in the Hb H-CS disease patients. Therefore, the CE method was superior to the HPLC method for detecting Hb CS. Furthermore, the level of Hb CS quantified by CE proved useful in screening heterozygotes and homozygotes with Hb CS as well as Hb H-CS disease.     

The Hb E (HBB: c.79G>A), Mean Corpuscular Volume,Mean Corpuscular Hemoglobin Cutoff Points in Double Heterozygous Hb E/– –SEA α-Thalassemia-1 Carriers are Dependent on Hemoglobin Levels

Identifying double heterozygosities in Hb E (HBB: c.79?G>A)/– –^SEA (Southeast Asian) (α-thalassemia-1) (α-thal-1) in patients first diagnosed as carrying Hb E is important in thalassemia control. Low Hb E, mean corpuscular volume (MCV) and mean corpuscular hemoglobin (Hb) (MCH) levels have been observed in this double heterozygosity. However, the cutoff points of these parameters have never been systematically established. Here, we analyzed Hb E and red blood cell (RBC) parameters in 372 Hb E patients grouped by Hb levels, by the status of – –^SEA and –α^3.7 (α-thal-2; rightward) deletions, to establish the cutoff points. Then, the established cutoff points were evaluated in 184 Hb E patients. It was found that the cutoff points of Hb E, MCV, MCH were significantly dependent on the Hb levels. In the group having Hb levels <10.0?g/dL, the cutoff points of Hb E, MCV and MCH were 21.2%, 64.9?fL and 21.0?pg, respectively, and were 25.6%, 72.8?fL and 23.9?pg, respectively, in the group having Hb levels 10.0–11.9?g/dL. Finally, in the group having Hb levels ≥12.0?g/dL, the cutoff points of Hb E, MCV and MCH were 27.1%, 76.7?fL and 25.3?pg, respectively. Thus, to screen for the double heterozygous Hb E/– –^SEA anomaly in patients initially diagnosed as carrying Hb E, the Hb levels must be taken into account in choosing the suitable cutoff points of these three parameters.     

Detection of Coinherited Hb H-Constant Spring/Paksé Disease and Hb E by Capillary Electrophoresis and High Performance Liquid Chromatography

A capillary electrophoresis (CE) method has been proven to be superior to a high performance liquid chromatography (HPLC) method in the detection of Hb H-Constant Spring/Paksé [Hb H (β4) Hb CS or α142, Term→Gln, TAA>CAA (α2)]/Paksé [α142, Term→Tyr, TAA>TAT (α2)]. It also has the ability to quantify Hb Bart’s (γ4). The aim of this study is to analyze the efficacy of the CE and HPLC in the detection of Hb H (β4)-CS/Paksé-E [β26(B8)Glu→Lys, GAG>AAG] disease. The laboratory results from July 2009 to July 2012 were reviewed at the Thalassemia Laboratory of the Associated Medical Sciences Clinical Service Center, Chiang-Mai University, Chiang-Mai, Thailand. The HPLC or CE method was used for the diagnosis of β-thalassemia (β-thal) and hemoglobinopathies, and molecular analysis was used for the diagnosis of α-thalassemia-1 (α-thal-1) Southeast Asian (SEA) and Thai type deletions, Hb CS and Hb Paksé. Hb H-CS-E was found in six samples and Hb H-Paksé-E was found in one sample, respectively. On the capillary electrophoregram, peaks of Hb Bart’s and Hb CS/Paksé were observed in all samples with the mean levels at 2.4 and 1.0%, respectively. These peaks were also presented on the HPLC chromatogram. However, the Hb CS/Paksé level could be quantified in only three of these seven (43.0%) samples. Therefore, CE was proven to be superior to HPLC in the detection of Hb H-CS/Paksé-E disease, which will assist in diagnostic, counseling and prevention programs for these diseases.     

Further Studies on Hemoglobin Hirosaki: Demonstration of its Presence at Low Concentration

Hb Brie Comte Robert, named for the place were the carrier resides, was found in a French Caucasian male, 36-year-old, presenting with polycythemia. The hematological data of the proband were as follows: RBC 5.74 × 10¹²/L (normal range 5.0 ± 0.5 × 10¹²/L), Hb (hemoglobin) 18.6 g/dL (normal range 15.0 ± 0.5 g/dL), PCV 0.543 L/L, MCV 94.6 fL, MCH 32.4 pg. The red cell mass was increased by approximately 20%. In contrast, the leukocyte and platelet counts were normal at 6.3 × 10⁹/L and 220 × 10⁹/L, respectively. Study of other members of the proband's family was not possible.     

Treatment failure may lead to accelerated fibrosis progression in patients with chronic hepatitis C

Chronic hepatitis C (CHC) patients with treatment failure (TF) remain at risk of continuing fibrosis progression. However, it has not been investigated whether there is an increased risk of accelerated fibrosis progression after failed interferon‐based therapy. We aimed to investigate long‐term influence of TF on fibrosis progression compared with untreated patients with CHC. We studied 125 patients with CHC who underwent paired liver biopsies from 1994 to 2012. Patients with advanced fibrosis were excluded from the analysis. Sixty‐three patients had TF, and 62 patients were treatment‐naïve (TN). Annual fibrosis progression rate (FPR) was calculated, and significant fibrosis progression (SFP) was defined as ≥2 stage increase in fibrosis during follow‐up. Multiple regression analyses were performed to find out independent predictors of FPR and SFP. Demographic characteristics and duration between paired liver biopsies were similar in TF and TN groups. Baseline alanine aminotransferase and gamma‐glutamyl transferase (GGT) levels (71 ± 31 vs 47 ± 22, P < 0.001 and 49 ± 39 vs 36 ± 28, P = 0.027, respectively), baseline mean fibrosis stage (2.2 ± 0.7 vs 1.9 ± 0.7, P = 0.018) and histologic activity index (6.3 ± 1.9 vs 4.3 ± 1.6, P < 0.001) were higher in the TF group compared with the TN group. In regression analyses, the strongest independent predictor of fibrosis progression was the GGT level (OR: 1.03, 95%CI 1.01–1.5, P < 0.001). Treatment experience (OR: 5.97, 95%CI 1.81–19.7, P = 0.003) also appeared as an independent predictor of both FPR and SFP. Failed interferon‐based CHC treatment may lead to accelerated FPR in the long‐term compared with the natural course.     

Insulin-like growth factor-1 deficiency determines increased intima-media thickness at common carotid arteries in adult patients with growth hormone deficiency

objective To investigate the role of IGF‐1 on intima–media thickness (IMT) at common carotid arteries by Doppler ultrasonography. subjects Thirty‐nine patients (17 women, 22 men, aged 25–70 years) with severe GH deficiency (GHD), 19 with normal and 20 with low IGF‐1 levels, and 39 sex‐, age‐ and body mass index (BMI)‐matched healthy controls. results Patients with GHD showed abnormalities in lipid profile, and increased fibrinogen levels, mean IMT (0·88 ± 0·26 vs. 0·69 ± 0·14 mm, P < 0·001), and systolic and diastolic peak velocity (P < 0·001) compared to controls. Eight patients (18%) and one control (2·1%, P = 0·04) had well‐defined plaques. In controls, but not in patients with GHD, mean carotid IMT was correlated with age (r = 0·78, P < 0·001). In both controls (r = ?0·82; P < 0·0001) and patients with GHD (r = ?0·84, P < 0·0001), serum IGF‐1 levels were inversely correlated with mean IMT at common carotid arteries. At the stepwise multiple regression, the variables most significantly related to IMT in GH‐deficient patients were total cholesterol levels (t = 5·2, P < 0·001), followed by disease duration (t = 2·4, P = 0·02), while in controls the variables most significantly related to IMT were IGF‐1 levels (t = ?9·9, P < 0·001), followed by low density lipoprotein (LDL)‐cholesterol levels (t = ?2·3, P = 0·02). Compared to patients with normal IGF‐1 levels, those with low IGF‐1 levels had lower high density lipoprotein (HDL)‐cholesterol levels (1·0 ± 0·2 vs. 1·3 ± 0·2 mmol/l, P = 0·0002), and higher glucose (54·3 ± 6·1 vs. 48·9 ± 5·9 mmol/l, P = 0·008), insulin (25·2 ± 6·8 vs. 18·8 ± 6·0 mUl/l, P = 0·004), total cholesterol (7·1 ± 1·1 vs. 4·9 ± 0·6 mmol/l, P < 0·0001), total/HDL‐cholesterol ratio (7·2 ± 1·8 vs. 3·9 ± 0·7, P < 0·0001), fibrinogen levels (319·8 ± 56·9 vs. 241·8 ± 53·0 mg/dl, P < 0·0001) and mean IMT at common carotid arteries (1·05 ± 0·25 vs. 0·69 ± 0·07 mm, P < 0·0001). Atherosclerotic plaques were found only in GH‐deficient patients with low IGF‐1 levels. conclusions GH‐deficient patients have alterations in lipid profile with an increase in the total/HDL‐cholesterol ratio, which is an index of increased cardiovascular risk, but only patients with IGF‐1 deficiency have increased IMT.     

Colonoscopy in elderly Asians: a prospective evaluation in routine clinical practice

OBJECTIVE: Colonoscopy is believed to be more complicated in elderly patients in Western countries. It is uncertain if the situation holds true among Asians. This study is to determine differences in colonoscopy performance and sedation complications between patients aged <65 years and those ≥65 years of age in an Asian population. METHODS: A prospective, cross‐sectional study of adults attending outpatient colonoscopy at a tertiary institution. Clinical and endoscopic data were obtained from all consenting adults. RESULTS: Two hundred and one patients (70 elderly and 131 aged <65 years) were enrolled. Compared to the patients aged <65 years, the elderly patients had similar levels of good (42.9%vs 45.8%), satisfactory (42.9%vs 33.6%) and poor (14.3%vs 20.6%) bowel preparations (P = NS). Cecal intubation was achieved in 60 (85.7%) of the elderly patients and 116 (88.5%) of the younger adults (P = NS). The differences in mean total colonoscopy duration was not significant (30 ± 13 vs 27 ± 11 min). Although the elderly patients received lower mean sedation doses of midazolam (4.7 vs 5.1 mg) and pethidine (37.8 vs 46.4 mg) compared to the younger adults, the hypotension rates were significantly higher in the elderly patients (7.1%vs 0.8%, P = 0.01). The elderly patients had in additional one or more co‐morbid illnesses (P = 0.001), with significantly higher rates of diabetes (P = 0.004), ischemic heart disease (P = 0.03), hypertension (P = 0.001) and stroke disease (P = 0.004). CONCLUSION: Colonoscopy performance in elderly Asians is similar to that in younger adults. However, the conscious sedation of these patients results in a higher rate of cardio‐vascular complications.     

An added value for the hemoglobin content in reticulocytes (CHr) and the mean corpuscular volume (MCV) in the diagnosis of iron deficiency in postpartum anemic women

Introduction: To evaluate the use of reticulocyte hemoglobin content (CHr) and mean corpuscular volume (MCV) to identify truly iron‐deficient women with postpartum anemia (PPA), in order to reduce unnecessary iron supplementation. Methods: Three hundred women with more than 500 mL of blood loss or clinical signs of anemia were divided in a control (Hb ≥ 10.5 g/dL, N = 150) and postpartum anemia group (PPA, Hb < 10.5 g/dL; N = 150). PPA women were given ferrous fumarate for a period of 4 weeks. Efficacy of the treatment was evaluated by comparing Hb, CHr, and MCV at baseline (T₀) and after 4 weeks (T₄). Using standard iron deficiency cut off values for MCV (80 fL) and CHr (28 pg) at T₀, we divided the PPA group of both parameters into two subgroups, one suggestive for iron deficiency and one suggestive for noniron deficiency. Results: Irrespective of the parameter or the subdivision, delta Hb concentrations (T₄–T₀) showed a similar increase in all PPA subgroups investigated. Both parameters in the PPA subgroups below their respective cut off value showed a significant improvement toward normalization, while the MCV and CHr in the PPA subgroups above their respective cut off value did not show any significant increase. Conclusion: Our data suggest that the etiology of the anemia in postpartum anemic women is not always iron deficiency. Using a combination of Hb, MCV and CHr, we increased the stringency to identify truly iron‐deficient postpartum anemic women, thereby reducing unnecessary iron supplementation in those women with sufficient iron stores.     

Risk factors for avascular necrosis among Filipino patients with systemic lupus erythematosus

Aim: To describe the clinical features and risk factors for avascular necrosis (AVN) in a cohort of Filipino patients with systemic lupus erythematosus (SLE). Methods: We reviewed the medical records of SLE patients with a diagnosis of AVN, seen at the University of Santo Tomas (Manila, Philippines) Section of Rheumatology, from 1995 to 2005. The diagnosis of AVN was based on clinical symptoms and confirmed by plain radiographs or magnetic resonance imaging. Possible risk factors for the development of AVN were identified. The clinical data of SLE patients without AVN were also obtained and served as controls. Results: Of the 540 patient charts reviewed, 43 (8.0%) patients (41 female, 2 male) with AVN were included. Out of a total of 66 joints involved, the hip was the most frequently involved. We included 93 SLE patients without AVN who were matched for age, sex and disease duration as the control group. Mean daily prednisone dose (11.9 ± 7.2 vs 9.3 ± 6.6 mg, P = 0.023), mean cumulative prednisone‐equivalent dose in first month of SLE diagnosis (1.5 ± 0.8 vs 1.3 ± 0.8 g, P = 0.011), and total cumulative prednisone‐equivalent dose (30.0 ± 2.7 vs 20.3 ± 1.9 g, P = 0.023) were higher in the AVN group than in the controls. Clinical variables significantly associated with AVN included the presence of vasculitis (OR = 4.45, 95% CI 1.65–12.18, P = 0.0007), the use of intravenous pulse steroids (OR = 2.92, 95% CI 1.21–7.08, P = 0.008), and the mean total cumulative prednisone‐equivalent dose ≥ 23.4 g (OR = 2.92, 95% CI 1.3–6.6, P = 0.007). Conclusion: Corticosteroid use and vasculitis were consistent risk factors seen among Filipino SLE patients who developed AVN during the course of their disease.     

Gender differences in the association between discharge hemoglobin and 12‐month mortality after acute myocardial infarction

Background

Anemia at discharge in patients with acute myocardial infarction is associated with poor prognosis; whether this differs in women and men or if there is a threshold value at which these relationships change is unknown.

Hypothesis

Women have a lower discharge hemoglobin (Hb) at which outcomes worsen.

Methods

We identified patients with acute myocardial infarction in the TRIUMPH registry between 2005 and 2008. In multivariable models, we evaluated the relationship between discharge Hb and 12‐month mortality and tested whether this relationship varied by gender. We assessed whether the relationship with discharge Hb values was nonlinear using a restricted cubic spline term.

Results

Of 4243 patients with AMI, 32.9% were female. Mean admission Hb was 12.9 ± 1.9 g/dL in women and 14.5 ± 2.0 g/dL in men, with mean discharge Hb 11.4 ± 1.8 g/dL and 12.9 ± 1.9 g/dL, respectively. Lower discharge Hb was independently associated with increased mortality (P < 0.05). In multivariable models, discharge Hb decline was similarly associated with increased 12‐month mortality in women and men (per 1‐g/dL decrease Hb; women HR: 1.24, 95% CI: 1.09‐1.42, P < 0.01; and men HR: 1.25, 95% CI: 1.13‐1.37, P < 0.01; P for gender interaction = 0.99). The relationship between discharge Hb and 12‐month mortality was linear (P for nonlinear spline term = 0.12).

Conclusions

Lower discharge Hb levels were similarly associated with increased 12‐month mortality in women and men. These relationships are linear without a clear threshold, suggesting any decline in discharge Hb is associated with poor outcomes.

     

Clinical manifestations of Behcet's disease in Chinese patients

Aim and method: The data of 1996 patients from 46 medical centres were meta‐analysed for the purpose of determining the type and frequency of clinical features of Behcet's disease in Chinese patients. The age at onset was 33.8 ± 12.2 years with 1144 male and 852 female patients. The duration of follow‐up at study entry was 8.9 ± 5.2 years. Results: The common manifestations observed throughout the disease course were oral aphthae (98.4%), genital aphthae (76.3%), various cutaneous lesions including erythema nodosum and pseudo‐folliculitis (69.0%), inflammatory ocular disease (34.8%) and arthralgia/arthritis (30.0%). Other systems, such as gastrointestines, vessels, nerves, heart, lungs, kidneys and blood, were also involved in Chinese Behcet's disease patients at the prevalence of 8.8%, 7.7%, 6.5%, 4.0%, 2.2%, 1.9% and 0.8%, respectively. Ophthalmologic presentation occurred earlier than the involvement of major vessels, gastrointestines, the nervous system and the haematological system. Vascular involvement as well as ocular, heart and nervous system involvement were more common in men than women (11.8%vs. 2.2%, P < 0.001, OR = 5.947; 39.9%vs. 27.9%, P < 0.001, OR = 1.715; 5.4%vs. 2.1%, P < 0.005, OR = 2.661; 8.0%vs. 4.5%, P < 0.05, OR = 1.845, respectively); while haematological involvement occurred more frequently in women than men (0.4%vs. 1.3%, P < 0.05, OR = 0.305) and gastrointestinal involvement was equally common in both sexes (8.3%vs. 9.4%, P > 0.05). Positive pathergy test was present in 57.9% of all patients and most of these were male (70%vs. 41.7%, P < 0.001). Conclusions: Behcet's disease starts frequently around the beginning of the third decade and has a male predominance. The disease is usually more severe in men than women in Chinese populations.     

Hematological Characterizations and Molecular Diagnostic Aspects of Hb Wiangpapao [α44(CE2)Pro→Ser (α1), CCG>TCG; HBA1: c.133C>T], a New α-Globin Variant Found in a Pregnant Thai Woman

We report the hematological parameters and provide a rapid molecular analysis method for detection of Hb Wiangpapao [α44(CE2)Pro→Ser, CCG>TCG; HBA1: c.133C>T], a new α-globin variant found in a pregnant Thai woman. Her red cell indices were measured by an automated blood counter. The results were: red blood cell (RBC) count 4.03?×?10¹²/L, Hb 13.1 (g/dL), packed cell volume (PCV) 0.39?L/L, mean corpuscular volume (MCV) 97.0 fL, mean corpuscular hemoglobin (Hb) (MCH) 32.5?pg, mean corpuscular Hb concentration (MCHC) 33.4?g/dL, and RBC distribution width (RDW) 9.4%. The Hb typing by high performance liquid chromatography (HPLC) showed 13.6% abnormal Hb at a retention time of 2.20?min. that was difficult to distinguish from Hb A. On the capillary electrophoresis (CE) electropherogram, this hemoglobinopathy peak did not separate from the Hb A peak. DNA sequencing showed a C>T transition at the first position of codon 44 (CCG>TCG) of the α1-globin gene that led to a substitution of proline for serine. This mutation has not been recorded in the public databases. Therefore, we named it Hb Wiangpapao as it was first discovered in the Wiangpapao District, Chiang Rai, Thailand. The multiplex allele-specific polymerase chain reaction (ASPCR) for detection of Hb Wiangpapao was developed and revealed a 510?bp specifically amplified fragment. The better understanding of hematological characterizations and the newly developed multiplex ASPCR for diagnosis of Hb Wiangpapao are useful for genetic counseling and family education.     

Determinants and characteristics of mean corpuscular volume and hemoglobin concentration in white HFE C282Y homozygotes in the hemochromatosis and iron overload screening study

Elevated mean corpuscular volume (MCV) is common in persons with hemochromatosis associated with HFE C282Y homozygosity. We evaluated data from the subset of non-Hispanic white participants in the Hemochromatosis and Iron Overload Screening Study to determine if elevated MCV in C282Y homozygotes is related to this genotype or to serum iron measures. Regression analysis was used to model MCV and Hb from transferrin saturation (TfSat), serum ferritin (SF), mean corpuscular hemoglobin concentration, red blood cell count, age, HFE genotype, Field Center, and presence of liver-related abnormalities in C282Y homozygotes and control subjects without HFE mutations (wt/wt genotype). Mean MCV was higher in C282Y homozygotes than in HFE wt/wt controls (94.4 vs. 89.7 fL in women; 95.3 vs. 91.2 fL in men; P < 0.0001 for both). These differences were largely associated with increased mean TfSat and SF in C282Y homozygotes. Adjusted mean MCV was 92.0 fL (95% confidence interval, 91.1, 92.9) in female C282Y homozygotes and 90.9 fL (90.3, 91.5) in controls. Among women with SF in the reference range 20-200 microg/L, adjusted mean MCV was 92.9 fL, (91.7, 94.2) in C282Y homozygotes, 1.8 fL higher than in controls (P = 0.013). The adjusted mean MCV of male C282Y homozygotes and controls was similar (P = 0.30). Adjusted mean Hb was 0.2 g/dL higher in women with C282Y/C282Y than in controls. Greater mean MCV in C282Y homozygosity reflects increased mean TfSat and mean SF in men and women; an additional effect of genotype on MCV and Hb was detected in women.