Apixaban, a direct oral anticoagulant is administered for stroke prevention in atrial fibrillation patients. Dosing adjustment is guided by renal function, age, and body weight. However, no data exist on its pharmacokinetics in patients with a body mass index (BMI) ≥ 35 kg/m2. The aim was to investigate the effects of BMI ≥ 35 kg/m2 on trough plasma concentrations of apixaban in patients with atrial fibrillation. This prospective study compared steady-state trough concentrations of apixaban in patients with a BMI ≥ 35 kg/m2 and patients with a BMI < 35 kg/m2. Sixty patients were included. In patients receiving 5 mg apixaban twice daily, the median trough plasma concentration was 29

The blood counts of α thalassemia carriers (α-thal) are similar to those of β thalassemia carriers, except for Hemoglobin A2 (Hb A2), which is not elevated. The objective of this study was to determine whether mathematical formulas are effective for detecting suspected α-thal. The data were obtained from the database of the prevention program for detecting couples at risk for having a child with hemoglobinopathy. Red Blood Cells (RBC) indices were analyzed using mathematical formulas, and the sensitivity and negative predictive value (NPV) were calculated. Among 1334 blood counts suspected of α-thal analyzed, only the Shine and Lal and the Support Vector Machine formulas revealed high sensitivity and NPV. Sensitivity was 85.54 and 99.33%, and NPV was 98.93 and 99.93%, respectively. Molecular defects were found in 291, and 81 had normal α genes. Molecular analysis was not performed in 962 of the samples. Based on these results, mathematical formulas incorporating one of these reliable formulas for detecting suspected α or β thalassemia carriers in the program of the automatic analyzers can flag these results, increase the awareness of the primary physicians about the carrier risk, and send an alert with a recommendation for further testing.

Immediate vs on-demand maternal oral full feeding

The membrane-bound hemoglobin (Hb) fraction impacts red blood cell (RBC) rheology and metabolism. Therefore, Hb-RBC membrane interactions are precisely controlled. For instance, the signaling function of membrane-bound deoxy-Hb and the structure of the docking sites in the cytosolic domain of the anion exchanger 1 (AE-1) protein are well documented; however, much less is known about the interaction of Hb variants with the erythrocyte's membrane. Here, we identified factors other than O2 availability that control Hb abundance in the membrane-bound fraction and the possible variant-specific binding selectivity of Hb to the membrane. We show that depletion of extracellular Ca2+ by chelators, or its omission from the extracellular medium, leads to membrane-bound Hb release into the cytosol. The removal of extracellular Ca2+ further triggers the redistribution of HbA0 and HbA2 variants between the membrane and the cytosol in favor of membrane-bound HbA2. Both effects are reversible and are no longer observed upon reintroduction of Ca2+ into the extracellular medium. Fluctuations of cytosolic Ca2+ also impact the pre-membrane Hb pool, resulting in the massive transfer of Hb to the cellular cytosol. We hypothesize that AE-1 is the specific membrane target and discuss the physiological outcomes and possible clinical implications of the Ca2+ regulation of the intracellular Hb distribution.

BACKGROUND: During the postpartum period, enoxaparin is given to high-risk women to prevent venous thromboembolism, a leading cause of maternal mortality. Enoxaparin activity is measured by peak plasma anti-Xa levels. The prophylactic range of anti-Xa is 0.2 to 0.6 IU/mL. Values above and below this range represent subprophylactic and supraprophy-lactic levels, respectively. Weight-based enoxaparin administration was superior to fixed-dose enoxaparin administration in achieving an anti-Xa prophylactic range. However, it is unknown which weight-based enoxa-parin administration is superior (once daily weight categories vs 1 mg/kg body weight).OBJECTIVE: This study aimed to compare the efficacy in reaching pro-phylactic anti-Xa levels and adverse effects profile of the 2 weight-based enoxaparin dosing protocols.STUDY DESIGN: A randomized open-label controlled trial was con-ducted. Women after delivery, who were intended to receive enoxaparin, were randomized to receive either enoxaparin treatment according to 1 mg/kg (up to 100 mg) or weight categories (& LE;90 kg, 40 mg; 91 -130 kg, 60 mg; 131-170 kg, 80 mg; >170 kg, 100 mg). Plasma anti-Xa levels were obtained 4 hours after the second enoxaparin administration (day 2 of enoxaparin treatment). If the woman was still hospitalized, anti-Xa levels were also obtained on day 4. The primary endpoint was the proportion of women with anti-Xa levels within the prophylactic range at day 2. In addi-tion, data regarding anti-Xa levels in different weight groups and rates of venous thromboembolism and adverse effects were evaluated.RESULTS: Of note, 60 and 64 women received enoxaparin according to 1 mg/kg and weight categories, respectively; moreover, 55 (92%) and 27 (42%) women reached the prophylactic range of anti-Xa at day 2, respec-tively (P<.0001). The mean anti-Xa levels on day 2 were 0.34+0.09 and 0.19+0.06 IU/mL, respectively (P<.0001). The anti-Xa levels were higher in the 1 mg/kg group than in the weight categories group in the subanaly-sis of different weight categories (51-70, 71-90, and 91-130 kg). There was no difference in anti-Xa levels on day 4 compared with day 2 in both cohorts (n=25). There was no case of supraprophylactic anti-Xa levels, venous thromboembolism events, or serious hemorrhage.CONCLUSION: Postpartum enoxaparin administration at 1 mg/kg was superior to weight categories in reaching anti-Xa prophylactic levels with-out leading to serious adverse effects. Given the high efficacy and safety profile, enoxaparin at 1 mg/kg once daily should be considered the pre-ferred protocol for postpartum venous thromboembolism prophylaxis.

Background Chronic kidney disease patients are at increased risk of mortality with cardiovascular diseases and infections as the two leading causes of death for end-stage kidney disease treated with hemodialysis (HD). Mortality from bacterial infections in HD patients is estimated to be 100-1000 times higher than in the healthy population. Methods We comprehensively characterized highly pure circulating neutrophils from HD and healthy donors. Results Protein levels and transcriptome of HD patients' neutrophils indicated massive neutrophil degranulation with a dramatic reduction in reactive oxygen species (ROS) production during an oxidative burst and defective oxidative cellular signaling. Moreover, HD neutrophils exhibit severely impaired ability to generate extracellular NET formation (NETosis) in NADPH oxidase-dependent or independent pathways, reflecting their loss of capacity to kill extracellular bacteria. Ectopic hydrogen peroxidase (H2O2) or recombinant human SOD-1 (rSOD-1) partly restores and improves the extent of HD dysfunctional neutrophil NET formation. Conclusions Our report is one of the first singular examples of severe and chronic impairment of NET formation leading to substantial clinical susceptibility to bacteremia that most likely results from the metabolic and environmental milieu typical to HD patients and not by common human genetic deficiencies. In this manner, aberrant gene expression and differential exocytosis of distinct granule populations could reflect the chronic defect in neutrophil functionality and their diminished ability to induce NETosis. Therefore, our findings suggest that targeting NETosis in HD patients may reduce infections, minimize their severity, and decrease the mortality rate from infections in this patient population.

Introduction: The commonly used method for hematocrit detection, by visual examination of microcapillary tube, known as "micro-HCT", is subjective but still remains one of the key sources for false hematocrit evaluation. Analytical automation techniques have increased standardization of RBC indexes detection; however, indirect hematocrit measurements by blood analyzer, the automated HCT, does not correlate well with "micro-HCT" results in patients with hematological pathologies. We aimed to overcome those disadvantages in "micro-HCT" analysis by using "ImageJ", processing software. Methods: 223 blood samples from the "general population" and 19 from sickle cell disease patients were examined in parallel for hematocrit values using the automated HCT, standard "micro-HCT" and "ImageJ" micro-HCT methods. Results: For the "general population" samples, the "ImageJ" values were significantly higher than the corresponding values evaluated by standard "micro-HCT" and automated HCT, except for the 0 to 2 months old newborns, in which the automated HCT results were similar to the "ImageJ" evaluated HCT. Similar to the "general population" cohort, we found significantly higher values measured by "ImageJ" compared to either "micro-HCT" or the automated HCT in SCD patients. Correspondent differences for the MCV and MCHC were also found. Conclusions: This study introduces "micro-HCT" assessment technique using the image-analysis module of "ImageJ" software. This procedure allows overcoming most of the data errors associated with the standard "micro-HCT" evaluation and can replace the use of complicated and expensive automated equipment. The presented results may be also used to develop new standards for calculations of hematocrit and associated parameters for routine clinical practice.

Dear Editor On July 29, 2021, the Israeli Ministry of Health approved the third anti-Coronavirus disease 2019(COVID-19) vaccination (3rd-BNT162b2-booster-dose), leading to a sharp daily drop in diagnosed positive COVID-19 cases and mortality rates in Israel [1]. The booster dose increased severe acute respiratory syndrome coronavirus-2(SARS-CoV-2) neutralization efficiency approximately a hundred-fold compared to individuals receiving only the second dose, providing significant protection against infection [2]. Due to their immunocompromised condition, cancer patients may be more susceptible and generally more vulnerable to infections [3]. Indeed, due to the chronic weakening of their immune system, cancer patients are at higher risk of developing severe clinical outcomes from SARS-CoV-2 infection and are associated with an increased risk of morbidity and mortality [3]. Cancer patients treated with anticancer drugs or undergoing major surgery have double the risk of developing a severe illness, hospitalization, and death due to COVID19 [3, 4]. Early studies on cancer patients in Israel who received the second BNT162b-booster-dose indicated a noticeable lag in antibody production compared to controls, despite the comparable seroconversion rate tested four weeks after administration [5]. No adverse effects or interaction between immunoglobulin G (IgG) levels and active anticancer therapies, such as chemotherapy or radiation, were reported [4]. Recently, a study evaluating immune response 4-weeks after administration by cancer patients receiving the 3rd-BNT162b2-boosterdose indicated an efficient anti-COVID-19 immunity when neither gender nor chemotherapy status was associated

Abstract Apixaban, a direct oral anticoagulant (DOAC) is administered in a fixed-dose regimen for atrial fibrillation patients. Dosage adjustment is based on renal function, age, and body weight (less than 60 kg). No data exist on the pharmacokinetics of apixaban in patients with body mass index (BMI) ≥ 35 Kg/m2, nor about treatment efficacy and safety in this population. Aims: To reveal whether BMI ≥ 35 kg/m2 affects trough plasma concentrations of apixaban in patients with atrial fibrillation and whether dose adjustment is required in this population. Methods: This prospective study compared steady state trough concentrations of apixaban in patients with BMI ≥ 35 kg/m2 and patients with BMI < 35 kg/m2. Results: Sixty patients were included in the study. In patients on 5 mg twice daily dose, the median trough plasma concentration was 29% lower in the high BMI group (BMI ≥ 35 kg/m2) compared with the lower BMI group (BMI < 35 kg/m2) (148.9 ng/ml, IQR: 94.5-205.6, compared to 209.1 ng/ml IQR: 167- 266.8 ng/ml respectively). P = 0.044. However, median trough concentrations were within the manufactures predicted steady-state apixaban exposure range. A similar trend was found among patients treated with 2.5 mg apixaban twice daily, but the results did not reach statistical significance. According to multivariate analysis performed, no correlation was found between BMI values (neither BMI ≥ 35 kg/m2 nor BMI < 35 kg/m2) and trough concentrations. Conclusion: Lower apixaban trough concentration was observed in patients with BMI ≥ 35 kg/m2 but remains within the steady-state apixaban exposure range found to be effective according to manufacturer data.

Autoimmune myelofibrosis (AIMF) is an uncommon cause of myelofibrosis associated with favorable outcome. Primary AIMF, AIMF without a known systemic autoimmune disorder, has been described in adults, but never in children. Here, we present, for the first time, an apparent case of primary AIMF in a 15-year-old boy admitted with profound hypoproliferative anemia.

Abstract Background: β-thalassemia (BT) is a hereditary hemolytic anemia. The imbalance between α- and β-globin chain synthesis results in ineffective erythropoiesis, severe microcytic hypochromic anemia and iron overload. Although regular transfusions and iron-chelation therapy markedly improve the survival and quality of life of BT patients, they have also led to the emergence of previously unrecognized complications. Patients with thalassemia major often present with endocrine abnormalities due to dysfunction of the hypothalamic-pituitary axis (Poggi, 2016), and are frequently underweight with abnormally low body-fat percentage (Fung, 2010). Adipose tissue stores lipids, but it also has an endocrine function through the production of leptin, an adipocyte-derived hormone that regulates food intake, metabolic and endocrine functions by activating its receptor in the central nervous system. Leptin plays a regulatory role in immunity and inflammation, and also seems to act synergistically with erythropoietin on mammalian hematopoiesis (Bennett, 1996). For example, a stimulatory effect of leptin on erythropoiesis among patients with end-stage renal disease was observed (Axelsson 2005). Previous studies on leptin in BT patients have shown lower levels than in healthy controls, and a negative correlation with the level of soluble transferrin receptor in transfused patients (Dedoussis, 2002). The reduced leptin levels were explained by a possible toxic effect of iron on adipocytes (Chaliasos, 2010). Study aims: In this study, we investigated the correlation between leptin level and anthropometric parameters in BT patients compared to heathy controls. We also explored the relationship between leptin and hematological and erythropoietic parameters, as well as iron-overload status in BT patients. Patients and methods: Transfusion-dependent BT patients (n = 33; 16 females, 17 males, mean age 23.5 ± 8.6 [range 8-41] years), treated at the Pediatric Hematology Unit of Emek Medical Center, and 11 healthy controls (6 females, 5 males, mean age 26.4 ± 10.4 [range 8-39] years) were studied. Patients were treated by regular blood transfusions and iron-chelation therapy. Anthropometric assessments included height, weight, fat percentage and BMI calculation. Blood samples were obtained at fasting and before blood transfusion. Serum leptin, complete blood count, hemoglobin and reticulocyte counts and serum erythropoietin were analyzed. These studies were performed twice, 3 months apart, and the mean values were utilized for the statistical analysis. Serum leptin levels were analyzed by radioimmunoassay, and leptin-normalized values were calculated (ng/dL leptin per % body fat). Results: BT patients were found to have lower leptin levels than healthy controls (5.4 ± 5.9 vs. 13 ± 10.1 ng/dL; p= 0.0006). Leptin levels were higher in females than in males (mean leptin 7.2 ± 6.5 vs. 3.7 ± 4.7 ng/dL; p= 0.01), and increased with age (r= 0.4635, p= 0.0066). A negative correlation was found between leptin and erythropoietin (r= -0.43473, p= 0.0115), and a positive correlation between leptin and hemoglobin, as well as the mean pre-transfusion hemoglobin levels in the previous 5 years (r= 0.66884, p < 0.001; r= 0.40261, p= 0.0202, respectively). No correlation was observed between leptin levels and anthropometric parameters (weight, height, BMI), iron-overload parameters or reticulocyte count. Fasting and normalized leptin showed similar patterns. Conclusions: This study confirms that BT patients are unable to maintain adequate leptin production, suggesting that adipose tissue dysfunction may be related to the chronic anemia. Our results correlate well with previous studies of lower leptin levels in BT patients. The positive correlation of leptin level with hemoglobin, together with the inverse correlation with erythropoietin provide further evidence of the effect of leptin on erythropoiesis. Additional studies are needed to examine the intricate interplay between adipose tissue, leptin and erythropoiesis in the environment of chronic anemia and iron overload present in BT patients. Disclosures No relevant conflicts of interest to declare.