Advances in Hematology

-thalassemia encompasses a group of monogenic diseases that have in common defective synthesis of -globin. The defects involved are extremely heterogeneous and give rise to a large phenotypic spectrum, with patients that are almost asymptomatic to cases in which regular blood transfusions are required to sustain life. As a result of the inefficient synthesis of -globin, the patients suffer from chronic anemia due to a process called ineffective erythropoiesis (IE). The sequelae of IE lead to extramedullary hematopoiesis (EMH) with massive splenomegaly and dramatic iron overload, which in turn is responsible for many of the secondary pathologies observed in thalassemic patients. The processes are intimately linked such that an ideal therapeutic approach should address all of the complications. Although -thalassemia is one of the first monogenic diseases to be described and represents a global health problem, only recently has the scientific community started to focus on the real molecular mechanisms that underlie this disease, opening new and exciting therapeutic perspectives for thalassemic patients worldwide.

Luca Melchiori

Sara Gardenghi

Stefano Rivella

-Thalassemia: HiJAKing Ineffective Erythropoiesis and Iron Overload

地中海贫血：劫持无效红细胞生成与铁超负荷

Universal in the United States (US) since 2006, newborn screening (NBS) programs for sickle cell disease (SCD) allow for early identification of the disease and, as an unintentional byproduct, identification of sickle cell trait (SCT). Unlike other carrier states, SCT is highly prevalent and is found in nearly 3 million Americans, which results in important reproductive implications. Currently, all NBS programs in the US are responsible for their own policies regarding SCT notification, and little is known about how SCT notification practices are performed and how these practices vary across NBS programs. We surveyed NBS programs personnel in all 50 states, the District of Columbia, and the US’ territories of Puerto Rico and Guam ( n = 53) using an electronic survey. There was a 100% response rate. All NBS programs (100%) provide notification of SCT status to either a pediatrician or parent: 49% notify the pediatrician only, 45% notify both the pediatrician and parent, and 6% notify the parent only. A total of 98% of NBS programs retain electronic records of SCT status, but only 38% can be directly accessed by pediatricians/primary care doctors. No state operates a publicly available database that allows individuals to access their own records. Only one state provides renotification at reproductive age. In conclusion, there is wide variability in NBS practices for SCT notification. This study demonstrates a need for national guidelines to standardize SCT notification across the US to ensure effective notification and counseling for SCT.

Jayla Lynn Scott

Jana Christian

Manuela Plazas Montana

Yvette M. Miller

Rakhi P. Naik

Variability in Notification of Positive Newborn Screening Results for Sickle Cell Trait Across the United States

美国各地镰状细胞性状新生儿筛查阳性结果通知的差异性

Objective: The present study aimed to evaluate for the first time, the early molecular response (EMR) to imatinib at 3 months for patients with chronic myeloid leukemia and to determine the predictive factors that influence poor outcome and response. Methods: 60 newly diagnosed CML patients were enrolled from May 2018 to June 2023. They received imatinib and prospectively underwent a molecular evaluation. Their EMR was assessed using a RT‐qPCR method and expressed as the BCR::ABL1 IS transcript level at 3 months. Potential factors impacting the EMR were identified using the Cox proportional hazard regression models. The effects of an EMR on the cumulative incidence of a deep molecular response (DMR) were also evaluated. Results: Out of the 60 CML patients recruited, 29 (48%) achieved an optimal response with TKI therapy after 3 months. The cumulative rate of molecular response was 16 (36%) for a major molecular response (MMR), 10 (23%) for MR4, 8 (18%) for MR4.5, and 6 (14%) for MR5, while 4 (9%) showed indetectable transcript. In addition, as 26 (90%) of patients with optimal response at 3 months showed a DMR, we determined that an optimal response to TKI at 3 months was significantly correlated with a DMR. We also identified through multivariate analysis that seven independent risk factors significantly influenced an EMR to TKI. These factors included male, late diagnosis, advanced performance status, the presence of splenomegaly, high‐ELTS risk groups, a BCR::ABL1 domain mutation, and complete hematologic response after more than 30 days. Conclusion: Our study demonstrates that an EMR at 3 months has a predictive value for a DMR. In addition, a MMR and a DMR can be predicted using a combination of parameters that either have a significant impact on the optimal response, or that can serve as prognostic indicators for molecular response, especially in low‐income countries, where molecular assessment and monitoring are not available or possible.

Kouassi Gustave Koffi

Sara Akou Bognini

Dohoma Alexis Silué

Ismael Kamara

Ines Kouakou

Emeraude N’dhatz

Boidy Kouakou

Danho Clotaire Nanho

David Tea Okou

Early Molecular Response to Imatinib First‐Line Therapy and Predictive Factors of Poor Outcomes for Chronic Myeloid Leukemia Patients in Côte d’Ivoire

伊马替尼一线治疗早期分子反应及科特迪瓦慢性髓性白血病患者不良预后预测因素

Based on the relationship between the intracellular concentration of sickle hemoglobin S (HbS) and the delay that occurs prior to the onset of sickling following deoxygenation, targeting the intracellular HbS concentration is a recognized therapeutic approach for sickle cell disease (SCD). We and others have shown that restricting iron by dietary or pharmacologic means improves hematologic parameters, inflammation, and organ damage in mouse models of SCD. Clinical evidence corroborating these findings is confined to case reports and small case series studies, none of which account for treatment or α ‐thalassemia. We hypothesize that increased transferrin saturation is associated with increased mean cellular hemoglobin concentration (MCHC) which in turn is associated with decreased red cell counts and worsening anemia. To investigate this hypothesis, we examined the relationships between transferrin saturation and MCHC with each of the parameters that define MCHC in sickle patients (HbSS without α ‐thalassemia) and healthy volunteers (HVs). Results indicate that transferrin saturation and MCHC are positively correlated with each other in sickle patients and HV. In patients with SCD, MCHC and transferrin saturation are negatively correlated with RBC count and are not correlated with hemoglobin, whereas each is positively associated with HV. Transferrin saturation and MCHC are each positively correlated with the hemolysis marker, lactate dehydrogenase. These observations support a model where increased transferrin saturation contributes to higher intracellular HbS concentrations with subsequent increases in sickling and hemolysis in sickle patients, suggesting that pharmacologic approaches to decrease serum iron may provide a therapeutic approach for patients with SCD. Trial Registration: This study was registered with ClinicalTrials.gov identifiers: NCT00011648 , NCT00081523 , and NCT04817670 .

Nermi L. Parrow

Jason M. Doherty

Anna Conrey

Swee Lay Thein

Robert E. Fleming

Relationships Between Markers of Iron Status and Hematological Parameters in Patients With Sickle Cell Disease

镰状细胞病患者铁状态标志物与血液学参数之间的关系

Background: Hydroxyurea (HU) is a disease‐modifying therapy with significant clinical and laboratory efficacy among individuals living with sickle cell anaemia (SCA). This is evident through increased fetal haemoglobin, higher packed cell volume, improved red cell hydration, reduced leukocytes, and platelet function. The effect on the coagulation pathway and pathophysiologic mechanism remains unclear, especially in children living with SCA. This study evaluated the coagulation profile using D‐dimer and thrombin antithrombin complex (TAT) in children with SCA. Methods: The cross‐sectional study was conducted over three months at LUTH among 80 children living with SCA in steady state aged 2–18 years (40 HU exposed and 40 HU naïve, respectively). Blood samples were assayed for D‐dimer, TAT, and complete blood count. Descriptive analysis such as mean and standard deviation for normally distributed variables or median and interquartile range for skewed data were used to summarize continuous variables, while proportion or percentages for categorical variables. Univariate analysis and bivariate analysis were done and statistical significance was set at p &lt; 0.05. Results: The mean age (±SD) of study participants in both groups was 11.35 (±4.6 years). D‐dimer levels (23.27 ng/mL) and TAT (29.79 pg/mL) were significantly lower among HU exposed compared to HU naïve children (62.73 ng/mL and 109.34 pg/mL, respectively) p &lt; 0.001. There was a negative correlation between D‐dimer and TAT with the duration of HU use ( r = −0.499, p = 0.001, and r = −0.401, p = 0.010), respectively. There was a positive correlation between D‐dimer and TAT with total WBC ( r = 0.368, p = 0.019, and r = 0.385, p = 0.014, respectively) among the HU naïve participants and a negative correlation between D‐dimer and TAT with haemoglobin level ( r = −0.303, p = 0.047, and r = −0.311, p = 0.041, respectively) among HU exposed children. Conclusion: HU modulates the D‐dimer and TAT levels of children living with SCA toward the normal reference range, thus reducing the risk of hypercoagulability and associated sequelae. Therefore, continuous advocacy for HU use should entail close monitoring of adverse effects.

Blessing E. Kene-Udemezue

Abideen O. Salako

Adeseye M. Akinsete

Oluwatosin O. Odubela

Titilope A. Adeyemo

A Comparative Analysis of Hydroxyurea Treatment on Coagulation Profile Among Sickle Cell Anaemia Children in Lagos, Nigeria

尼日利亚拉各斯镰状细胞贫血儿童羟基脲治疗对凝血谱的比较分析

Chronic kidney disease (CKD) is an important risk factor for cardiovascular disease, thrombosis, and all-cause death. However, few studies have examined the association between CKD and the prognosis of patients with essential thrombocythemia (ET). We collected ET patients who met the WHO classification 2017 and performed a retrospective clinical study to clarify the association between the presence and onset of CKD and prognosis. Of 73 patients who met the diagnostic criteria, 21 (28.8%) had CKD at the time of ET diagnosis. The age of patients with CKD was significantly higher, and a high proportion of these patients had the JAK2V617F gene mutation. The presence of CKD was a risk factor for the prognosis (hazard ratio (HR): 3.750, 95% confidence interval (CI): 1.196–11.760, <math xmlns="http://www.w3.org/1998/Math/MathML" id="M1"><mi>P</mi><mo>=</mo><mn>0.023</mn></math> ), and the survival curve was significantly poorer. Furthermore, we analyzed patients without CKD at the time of ET diagnosis using the onset of CKD as a time-dependent variable and identified the onset of CKD as a risk factor for the prognosis (HR: 9.155, 95% CI: 1.542–54.370, <math xmlns="http://www.w3.org/1998/Math/MathML" id="M2"><mi>P</mi><mo>=</mo><mn>0.005</mn></math> ). In patients with renal hypofunction at the time of ET diagnosis or those with a reduction in the kidney function during follow-up, strict renal function monitoring at regular intervals is necessary.

Yoshinori Hashimoto

Hiromi Omura

Takayuki Tanaka

Presence and Onset of Chronic Kidney Disease as a Factor Involved in the Poor Prognosis of Patients with Essential Thrombocythemia

慢性肾脏疾病的存在和发病作为原发性血小板增多症患者预后不良的因素

ISSN	1687-9104, 1687-9112
h-index	38

Publication Information	Publisher: Hindawi Limited，Publishing cycle: ，Journal Type: journal，Open Access Journals: Yes
Basic data	Year of publication: 2009，Proportion of original research papers: 0.00%，Self Citation Rate:N.A.， Gold OA Rate: 0.00%
Journal Fees	$820Details
Average review cycle	15 weeks

Advances in Hematology

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-Thalassemia: HiJAKing Ineffective Erythropoiesis and Iron Overload

Variability in Notification of Positive Newborn Screening Results for Sickle Cell Trait Across the United States

Early Molecular Response to Imatinib First‐Line Therapy and Predictive Factors of Poor Outcomes for Chronic Myeloid Leukemia Patients in Côte d’Ivoire

Relationships Between Markers of Iron Status and Hematological Parameters in Patients With Sickle Cell Disease

A Comparative Analysis of Hydroxyurea Treatment on Coagulation Profile Among Sickle Cell Anaemia Children in Lagos, Nigeria

Presence and Onset of Chronic Kidney Disease as a Factor Involved in the Poor Prognosis of Patients with Essential Thrombocythemia

Variability in Notification of Positive Newborn Screening Results for Sickle Cell Trait Across the United States

Early Molecular Response to Imatinib First‐Line Therapy and Predictive Factors of Poor Outcomes for Chronic Myeloid Leukemia Patients in Côte d’Ivoire

Relationships Between Markers of Iron Status and Hematological Parameters in Patients With Sickle Cell Disease

A Comparative Analysis of Hydroxyurea Treatment on Coagulation Profile Among Sickle Cell Anaemia Children in Lagos, Nigeria