Hemoglobin最新文献

Sickle cell disease (SCD) is an inherited hemoglobinopathy characterized by vaso-occlusion, hemolysis of red blood cells (RBC), and a predisposition for venous thromboembolism (VTE). The sickling and hemolysis of RBC culminate in coagulation system abnormalities, platelet activation, endothelial dysfunction, and impaired blood flow manifesting as a prothrombotic state. In addition, individuals with SCD are often exposed to extrinsic risk factors for VTE including recurrent hospitalizations, central venous catheters, and acute medical illnesses. The diagnosis is often challenging as symptoms may mimic other complications of SCD, and there is little data to guide diagnostic algorithms involving probability scoring in the SCD population. Non-anticoagulant strategies aimed at reducing disease severity may aid in lowering the risk of VTE, but data is limited. Furthermore, high quality evidence regarding anticoagulation in prevention and treatment of SCD is severely lacking, resulting in heterogeneity in clinical practice. In this narrative review we aim to review the prothrombotic pathophysiology of SCD, to describe the risk factors, high risk of mortality, and types of VTE in SCD, to develop an approach to the diagnosis of VTE in SCD, and to understand the limited available evidence for the prevention and treatment of VTE in SCD.

SUMMARYCOVID-19 infection has emerged as a comorbidity that can significantly increase morbidity and mortality in sickle cell patients with ACS (acute thoracic/chest syndrome). The aim of our study was to assess COVID-19-related morbidity and mortality in sickle cell patients with ACS. This was a retrospective, descriptive study of patient records followed over a 36-month period from January 2020 to December 2022. The study was conducted at the national blood transfusion center in Dakar. The sex ratio (M/F) was 0.82. The median age was 26 (17-39) years. The most represented age group was between 21 and 30 years. Factors associated with death were: at baseline, SS genotype, presence of comorbidities (asthma, chronic obstructive pulmonary disease, viral hepatitis B, ischemic heart disease), osteonecrosis of the femoral head, and use of NSAIDs (non-steroidal anti-inflammatory drugs) at diagnosis of COVID-19; at the diagnosis of ACS associated with COVID-19, respiratory distress, hypoxia (Sa02 < 92%), creatininemia >18.5 mg/l, CRP >192 mg/l, lymphopenia; the therapeutic modalities associated with death were: transfusion of RBCs (packed red blood cells) and curative anticoagulation. This study shows that patients with comorbidities and/or chronic complications of sickle cell disease can develop severe forms of ACS associated with COVID 19, leading to death. Other factors linked to death, notably diagnostic and therapeutic, were also identified in the course of this study.

Hb Youngstown [HBB:c.305A > C] is a rare unstable hemoglobin caused by the substitution of glutamic acid with alanine at codon 101 of the Beta globin chain. It causes hemolytic anemia in the heterozygous state. This is a case of a six-year-old Chinese-Javanese girl with heterozygous Hb Youngstown and clinical features of chronic hemolysis and iron overload. Hb Youngstown appears at the S window near to 4.6 minutes on high-performance liquid chromatography (HPLC) and can form a hybrid tetramer on alkaline gel electrophoresis seen as two distinct bands cathodal to A and close to F. For the first time, Hb Youngstown is captured with capillary electrophoresis (CE) and shown to be eluted at zone 8. Clinical presentation and Hb analysis results of this heterozygous Hb Youngstown overlap with heterozygous Hb Rush. They can only be differentiated at molecular level by Beta globin gene sequencing or intact mass spectrometry.

Background: Transfusion-dependent thalassemia (TDT) is an autosomal recessive disorder characterized by defective hemoglobin synthesis, leading to severe complications such as iron overload and multi-organ dysfunction. This study aims to elucidate the distinctive clinical and biochemical profiles of TDT patients compared to healthy controls, with an emphasis on cardiovascular risk assessment using novel markers such as the Plasma Atherogenic Index (PAI) and Triglyceride-Glucose (TyG) index.

Methods: This cross-sectional study included 32 TDT patients and 36 healthy controls, matched for age and gender. Comprehensive demographic, laboratory, and imaging data were collected and analyzed. TDT patients were further stratified based on cardiac involvement and ferritin levels. Key assessments included hemoglobin levels, liver enzymes, lipid profiles, and cardiac imaging. The PAI and TyG index were calculated to evaluate cardiovascular risks. Statistical analyses were performed using SPSS 27.0, employing Student's t-test, Mann-Whitney U test, and Pearson chi-square test as appropriate.

Results: No significant differences in basic demographic parameters were observed between groups; however, TDT patients exhibited significant clinical and laboratory differences. Notably, these patients had lower hemoglobin levels, higher platelet counts, elevated liver enzymes (ALT and AST), and markedly increased ferritin levels. Lipid profiles were significantly altered, with lower levels of total cholesterol, HDL, and LDL but elevated triglycerides. Importantly, the PAI was significantly higher in TDT patients, suggesting an increased atherosclerotic risk. Subgroup analysis revealed that patients with cardiac involvement had worse metabolic profiles, higher TyG indices, and prolonged QT intervals, indicating heightened cardiovascular risk. As the iron burden increases, the TyG index and PAI may lose their sensitivity in distinguishing between varying levels of iron overload, suggesting that their effectiveness plateaus beyond a certain threshold of iron accumulation.

Conclusion: TDT patients show significant hematological and metabolic deviations, including elevated cardiovascular risk markers like PAI and TyG index. As iron burden increases, these markers lose discriminative power, and cardiac involvement escalates rapidly once a critical iron threshold is surpassed, as supported by studies showing a non-linear relationship between iron load and cardiac complications. Comprehensive cardiovascular risk assessment and tailored management are essential for these patients. Future studies should focus on tracking cardiovascular risk progression and the effects of targeted interventions.

In order to document the prevalence, clinical features, hematology and outcome of the aplastic crisis in homozygous sickle cell disease (HbSS), a cohort study has been conducted from birth. Newborn screening of 100 000 deliveries at the main government maternity hospital, Kingston, Jamaica between 1973 and 1981 detected 311 cases of HbSS who have been followed at the Medical Research Council Laboratories at the University of the West Indies, Kingston, Jamaica. Clinically defined aplastic crises occurred in 118 (38%) patients at a median age of 7.5 years (range 0.5-23.0 years). All but one event seroconverted to parvovirus B19, the exception being a 9.3 year male with classic aplasia but subsequent IgG did not exceed 3 IU. Defined by zero reticulocyte counts, 94 patients presented with a median hemoglobin of 3.7 g/dL (range 18-87 g/L) representing a median fall from steady state levels of 3.8 g/dL. Clear epidemic peaks occurred at 1979-1980, 1984-1986, and 1990-1993 and the admission rate and use of blood cultures fell with each epidemic, reflecting increased familiarity with the complication. Symptoms were usually nonspecific and all but 7 were transfused. No patient had a recurrence and two died from aplasia (one with remote rural residence and the other following an incorrect diagnosis). Of those seroconverting to parvovirus B19, 68% manifested aplasia and 24% had no hematologic change. Correctly diagnosed and managed, the aplastic crisis is essentially benign. (230 words).

α-thalassemia major (α-TM) often causes Hb Bart's (c4) hydrops fetalis and severe obstetric complications in the mother. Step-wise screening for couples at risk of having offspring(s) affected by α-TM is the efficient prevention method but some rare genotypes of thalassemia cannot be detected. A 32-year-old male with low HbA2 (2.4%) and mild anemia was performed real-time PCR-based multicolor melting curve analysis (MMCA) because his wife was -^SEA deletion carrier. The result of multiplex ligation-dependent probe amplification (MLPA) suggested the existence of -^SEA deletion in the proband. A novel deletion of the α-globin gene cluster was found using self-designed MLPA probes combined with longer PCR, which was further accurately described to be 16.8Kb (hg38, Chr16:1,65,236-1,82,113) deletion by the third-generation sequencing. A fragment ranging from 1,53,226 to 1,54,538(GRch38/hg38) was identified which suggested the existence of the homologous recombination event. The third-generation sequencing is accurate and efficient in obtaining accurate information for complex structural variations.

We report a new low-affinity hemoglobinopathy (Hemoglobin Oviedo) in a family with isolated low oxygen saturation (89-92%) caused by a previously undescribed variant (NM_000518.5: c.115A > G;p.Thr39Ala) in the hemoglobin subunit β encoding gene (HBB gene) located on chromosome 11.

Hemoglobin Strasbourg is a rare high oxygen affinity hemoglobin variant which leads to secondary erythrocytosis. This variant is caused by a HBB gene mutation c.71T > A resulting in an amino acid exchange on position 23 of the β globin chain (p.Val23Asp.). The influence of Hb Strasbourg on HbA1c measurement has not been studied to date. For patients with hemoglobin variants it is important to know whether possible interferences exist with the measurement of HbA1c. We therefore investigated the influence of Hb Strasbourg on HbA1c measurement with two different HPLC (high-performance liquid chromatography) systems and one turbidimetric immunoassay in two non-diabetic brothers who are heterozygous carriers of Hb Strasbourg. The examined tests are all used in routine diagnostics. In the case of Hb Strasbourg, the HbA1c measured by HPLC showed lower results than those obtained by the immunoassay. We conclude that HbA1c is underestimated when measured with these methods as glycated Hb Strasbourg is most likely not co-eluting with HbA1c in HPLC.

Copy number variations (CNVs) involving the α-globin gene cluster can lead to an imbalance in the proportion of α- and β-globin chains and consequently cause clinical symptoms of β-thalassemia. In our case, a 6-year-old boy, clinically diagnosed with β thalassemia intermedia, was admitted for further genetic diagnosis with his family. Targeted sequencing and third generation sequencing (TGS) were used to detect the possible variants of the thalassemia genes. Low-pass whole genome sequencing (lpWGS) was conducted to specify the exact location of relevant CNVs across the genome, which was then validated by multiplex ligation-dependent probe amplification.The results revealed that the patient had a heterozygous β⁰ mutation of Codon17 (A > T) and a full duplication of the α-globin gene cluster, inherited from his mother and father, respectively. Besides, a novel point mutation within the 5' untranslated region of β-Globin (HBB: c. -175 (G > A) was only detected in the patient. This study suggests that lpWGS seems a powerful alternative to detect large CNVs related to thalassemia with second intention for more information of the breakpoints and a simultaneous genome-scale detection of other pathogenic CNVs.