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Review Article | DOI: https://doi.org/10.31579/2692-9392/187
Department of Pediatrics, College of Medicine and Health Sciences - UAE University, Alain City, United Arab Emirates
*Corresponding Author: Abdul-Kader Souid, Department of Pediatrics, College of Medicine and Health Sciences - UAE University, Alain City, United Arab Emirates.
Citation: Shamma AlZaabi, Abdul-Kader Souid, (2023), A Brief Guide on Pediatric Hematology, Archives of Medical Case Reports and Case Study, 7(5); DOI:10.31579/2692-9392/187
Copyright: © 2023, Abdul-Kader Souid. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 27 October 2023 | Accepted: 01 November 2023 | Published: 06 November 2023
Keywords: diabetes case reports; drug design and development; emergency medicine; ethical issues
Reference (‘normal’) values of the complete blood count (CBC) vary with age and gender. Hematocrit, mean cell hemoglobin (MCH) and mean cell hemoglobin concentration (MCHC) are calculated quantities and have limited clinical use. Moreover, the white blood cell (WBC) count, the sum of the more important differential counts, has also limited clinical use.
Reference (‘normal’) values of the complete blood count (CBC) vary with age and gender. Hematocrit, mean cell hemoglobin (MCH) and mean cell hemoglobin concentration (MCHC) are calculated quantities and have limited clinical use. Moreover, the white blood cell (WBC) count, the sum of the more important differential counts, has also limited clinical use. Percentage counts are not needed [1].
Proper clinical interpretation of the neutrophil, lymphocyte, monocyte, eosinophil, and basophil counts is essential. For example, a consistent neutrophil or lymphocyte count of <1>400 x109/L are thrombocytosis (most commonly reactive).
Hemoglobin concentration. Normal hemoglobin concentration varies with age. Higher values occur in the newborn and in the adolescent male (Table 1). The low fetal arterial oxygen tension (PO2) of ~30 mm Hg stimulates erythropoietin secretion, leading to secondary polycythemia. After birth, the rise in arterial PO2 to ~90 mm Hg suppresses erythropoietin secretion, leading to a gradual decline in the red cell production that nadirs at ~2 months (physiologic anemia). This effect is steeper and occurs earlier in preterm neonates (with a typical hemoglobin concentration of 80 to 90 g/L by 1 to 2 months). Subsequently, a steady rise in hemoglobin concentration reaches maximum in post-pubertal males due to the effects of testosterone. The blood volume of a neonate increases by allowing emptying of placental vessels before cord clamping; a maximum delay in cord clamping of 60 seconds is recommended. Hemoglobin concentration is also influenced by the blood sampling technique; heel stick samples are less reliable than venous samples.
Red blood cells (RBC). The normal RBC count ranges from 3.5 to 6.5 x1012/L. About 1% to 2% of the circulating red cells are reticulocytes (immature non-nucleated red cells containing ribonucleic acid). Thus, the normal reticulocyte count ranges from 35 to 130 x109/L; values <35>130 x109/L reticulocytosis (Table 2). The nadir of reticulocyte count occurs between one week and 2 months, which results in physiologic anemia; a high reticulocyte count during this period signifies hemolysis. Nucleated red cells are seen in the first week of life; their presence after one week signifies prenatal/ perinatal hypoxia, hemorrhage or hemolysis. After the newborn period, circulating nucleated red cells indicate increased demand for production (e.g., hemorrhage or hemolysis) or bone marrow destruction (infiltration).
Mean cell volume (MCV). Red cell volume is expressed in femtoliter (fL = 10-15 L). Its value is determined using a calibrated electrical impedance (mean height of the voltage pulses generated during red cell counting). The red cells are macrocytic at birth, with MCV of 98 fL to 116 fL. MCV <94>98 fL indicates macrocytosis (e.g., B12 deficiency, which could be masked by a coexisting thalassemia trait, especially in a population with high prevalence of a-thalassemia trait). At one month of age, the lowest normal MCV is 70 fL. Thereafter, the lowest normal is “70 fL + y of age until 10 y”. Thus, MCV <70>
Relative distribution width (RDW = ‘standard deviation ÷ MCV’ [unitless, expressed as percentage) is a measure of the variation of red cell volume (relative standard deviation, coefficient of variation, degree of spread/ dispersion around the mean, anisocytosis). Normal RDW is <15>
II. Microcytic, Macrocytosis and Normocytic Anemias
Microcytosis (small red cells) signifies a decreased hemoglobin synthesis, usually due to iron deficiency (e.g., nutritional, milk-induced colitis, or hemorrhage), thalassemia trait (decreased a or b chain synthesis), chronic inflammation (blocks iron delivery to erythroid precursors), or [rarely] ineffective protoporphyrin
synthesis (e.g., hereditary sideroblastic anemia). Macrocytosis (large red cells), on the other hand, signifies impaired red cell production (e.g., adverse effect of a medication, B12 deficiency, or bone marrow failure syndrome). Normocytic (normal red cell size) hemolytic anemia is associated with jaundice, indirect hyperbilirubinemia, reticulocytosis, and splenomegaly. Examples include hemoglobinopathy (e.g., sickle cell disease), enzymopathy (e.g., glucose-6-phosphate dehydrogenase [G6PD] deficiency), cytoskeletal (membrane) abnormality (e.g., hereditary spherocytosis), and autoimmune hemolytic anemia.
III. Disorders Related to Iron
Iron bioavailability requires: (1) Ferritin, (2) Transferrin, (3) Transferrin receptor, and (4) Iron-responsive element (IRE) binding protein (IRE-BP, an mRNA-binding protein that senses cellular iron). Ferritin sequesters cellular iron for prompt mobilization when needed. Transferrin carries iron in the plasma. Transferrin receptors bind and internalize the transferrin-iron complex. IRE-BP coordinates the production of ferritin and transferrin receptors. If cellular iron is low, IRE-BP binds to IRE in the 5’ untranslated regions of mRNA, stimulating the translation of transferrin receptor and inhibiting the translation of ferritin; thus, promoting iron uptake and decreasing iron storage. The opposite occur in iron overload.
The “divalent metal transport protein-1” (DMT-1) is found on the apical membrane of enterocytes (mainly in the duodenum and upper jejunum); it mediates cellular Fe2+ uptake. Iron then exists the cell via the transmembrane exporter ferroportin. Ferroportin is inhibited by hepcidin [2]. Of note, celiac disease should be considered in the diagnostic evaluation of children with iron deficiency [3-4]. Their oral iron is unlikely to be absorbed until the intestines recover (with the elimination of gluten). For these children, parenteral iron is recommended [5-6].
The gastric acid, ascorbic acid, citric acid (juices), lactose (sugars) reduce Fe+3 to Fe+2, thus, increasing the bioavailability of dietary non-heme iron. Ascorbic acid also prevents binding of Fe+3 to plant phytates found in grains, such as oat, and rye, and polyphenols (e.g., tannins found in green tea, which binds iron and lowers its absorption).
Hepcidin, a critical regulator of iron bioavailability, is a hepatic hormone stimulated by iron and inflammation, and suppressed by iron deficiency, erythropoietin, hypoxia, and ineffective erythropoiesis [2]. Hepcidin inhibits iron absorption by binding to ferroportin and causing its internalization and degradation. Hepcidin also reduces iron efflux from macrophages and hepatocytes. Moreover, cytokines (e.g., lipopolysaccharide and interleukin-6) induce the release of hepatic hepcidin, resulting in iron sequestration in macrophages and ‘anemia of inflammation’. Low hepcidin, on the other hand, leads to increased iron absorption and export.
Absorbed Fe+2 is either stored as ferritin or exists the enterocyte through the basolateral membrane into the blood capillary; this transport is mediated by ferroportin (depicted in the shown schema). Ferroportin is present on the basolateral membrane and the membranes of macrophages, hepatocytes, and placenta. In the blood, transferrin binds exported iron and delivers it to the bone marrow and liver via the cell surface transferrin receptors.
Physiologic responses to iron deficiency include: (1) Low serum ferritin (levels <12 xss=removed xss=removed>
Inflammation and damages to ferritin-rich tissues (e.g., liver) elevate serum ferritin independent of iron stores. Serum ferritin is increased in inflammation; sTfR is not affected by inflammation; thus, sTfR is used to differentiate anemia of inflammation from iron deficiency.
MRI-based Ferriscan is a reliable indicator of liver iron. Children with thalassemia major require iron chelation when serum ferritin is >1,000 ng/mL. MRI-based Ferriscan scan for liver iron quantitation is then requested at annual intervals to guide iron chelation. If the estimated liver iron is >15 to 25 mg Fe/g dry weight liver, MRI-based Ferriscan quantitation of cardiac iron should also be done. Chelation with one or two drugs should be utilized to maintain liver iron between 3 and 7 mg Fe/g dry weight liver and normal cardiac iron. Of note, liver iron (measured in a biopsy sample) is limited by the variable iron content throughout the liver (e.g., missing foci of hepatic fibrosis).
Transfusional iron (expressed in ‘mg iron per kg’) can be estimated as: ‘Total volume of transfused red cells (in mL) x 0.6 (the average hematocrit in red cell bags) x 0.8 to 1.0 mg (the amount of iron per mL of transfused red cells; as 0.8 to 1.0 mg iron is acquired for every mL of red cells transfused) ÷ patient weight (kg)’. Liver iron (expressed in ‘mg iron per g dry liver weight’) is estimated as: ‘Transfusional iron (mg/kg) ÷ 10.6’. Liver iron content of 15 to 20 mg/gram dry weight is associated with liver fibrosis. Chelation is recommended when liver iron is >7 mg/g dry weight liver.
Children with ‘ineffective erythropoiesis’, such as thalassemia intermedia should have their first liver Ferriscan at 10 y of age and
every year thereafter depending on the results. In the absence of any transfusion, their mean annual increase of hepatic iron typically is 0.38 ± 0.49 mg Fe/g dry weight liver, which is mediated by suppressed hepcidin, causing increased iron absorption. At this rate, iron accumulation leads to serious complications in young adults, such as hepatic fibrosis, cardiac dysfunction, renal tubular dysfunction, hypogonadism, diabetes, hypoparathyroidism, and infertility.
Haptoglobin (the primary hemoglobin-binding protein in plasma) and hemopexin (promotes detoxification of heme when haptoglobin is depleted) are responsible for intravascular iron salvages. Haptoglobin and hemopexin are acute phase reactants; their levels are increased in infection/ inflammation. Both haptoglobin and hemopexin prevent free hemoglobin from being filtered through the kidney. Haptoglobin is the major hemoglobin-binding protein during intravascular hemolysis. Free hemoglobin binds to haptoglobin; while free heme binds to hemopexin. The heme-hemopexin complex is metabolized in the liver. The hemoglobin-haptoglobin complex (>150 kD) is internalized by CD163 (the monocyte-macrophage surface receptor) in ‘red pulp’ macrophages of the spleen and in Kupffer cells of the liver. The CD163 gene is induced by glucocorticoids, increasing the clearance of hemoglobin-haptoglobin.
About 70% of the body iron is in heme (hemoglobin and myoglobin), 29% in ferritin or hemosiderin (storage forms of iron), and <1>
An average diet contains two forms of iron: (1) Heme (10%, mainly Fe2+) and (2) Non-heme (90%, mainly Fe+3). Only 1-2 mg (10% of dietary iron) is absorbed daily. About 25% of heme iron (meat, poultry and fish) is absorbed, while only 5% non-heme iron (cereals, beans, and vegetables) is absorbed.
IV. Iron deficiency anemia (IDA)
Iron deficiency anemia (IDA) is common in early childhood. It is characterized by decreased hemoglobin, low MCV (microcytosis due to decreased hemoglobin synthesis), high RDW (heralds the production of smaller red cells), and reticulocytopenia (iron-limiting erythropoiesis). Children between 6 mo and 3 y are especially susceptible due to inadequate dietary iron for their rapid growth. In the first 4-6 mo, most full-term infants have adequate iron transferred through the placenta during the last trimester of pregnancy. Thus, premature infants frequently develop iron deficiency. In infants, cow’s milk induces colitis (gastrointestinal bleeding); thus, whole milk should not be introduced in the first year. The most conclusive evidence of iron deficiency anemia is iron-responsive anemia (iron-rich food [preferred as other micronutrient deficiencies are likely to coexist] with or without iron supplementation [depending on the severity]). Optimal response is obtained with 2 to 6 mg/kg/day of elemental iron; ferrous sulfate is the preferred form. The reticulocyte count increases in one week, followed by a gradual correction over 4 weeks. Treatment should continue for 3 mo [9-10].
Recommendations to prevent iron deficiency include iron supplement (1 to 2 mg/kg/day) to exclusive breast-fed infants after 4 mo; use of iron-fortified formulas (12 mg/L iron as ferrous sulfate) and cereals; iron supplement (2 to 3 mg/kg/day) for preterm infants after first mo; and delay cow’s milk until after first year [9-10].
Iron deficiency may result in impaired growth, poor school achievement, delayed motor and cognitive development, impaired immune responses, hyperactivity, and socio–emotional problems. Lower scores in the Bayley Scales of Infant Development have been demonstrated at 9 to 12 mo between non-anemic, iron deficient, and iron-sufficient infants. Dietary supplements from early age is a public health solution to this common problem [11-12].
V. Thalassemia
(Greek: thalatta or thalassa = sea’ –aima = blood; originating around the Mediterranean and Black Seas, hence the origin of the name, “Mediterranean Anemia”)
These inherited disorders are characterized by decreased synthesis of the a- or b-chain. Synthesis of the a-chain peaks at 3 mo of fetal age and b-chain peaks at 3 mo after birth. Thus, a-thalassemia manifests at birth and b-thalassemia after 3 mo of life. Single gene copies of the b (hemoglobin-beta locus; HBB, MIM#141900), d (hemoglobin-delta locus; HBD, MIM#142000), g (hemoglobin, gamma A; HBG1, MIM#142200 and hemoglobin, gamma G; HBG2, MIM#142250), and epsilon (e) are mapped to each allele of chromosome 11 (as shown in the schema).
Two copies of the a gene (hemoglobin-alpha locus 1; HBA1, MIM#141800 and hemoglobin-alpha locus 2; HBA2, MIM#141850) are mapped to each allele of chromosome 16. Thus, a normal individual has four a genes. The four chains (a, b, g, and d) form the three normal hemoglobin variants (Table 5): (1) Hb A (93% to 97%, two a plus two b), (2) Hb A2 (two a plus two d), and Hb F (two a plus two g). Since Hb A2 and F do not contain b chain, b-
thalassemia trait is associated with higher percentages of A2 and F. In a-thalassemia, the percentages of Hb A2 and F remain normal. Thus, accurate determination of A2 is crucial, as a slight (≥0.5%) elevation of A2 signifies b-thalassemia trait. Children with b-thalassemia major (homozygous b-thalassemia, two defective b genes) have severe microcytic anemia and depend on blood transfusion. The variant either abolish (b0) or reduce (b+) b-chain synthesis.
There are four a-thalassemia syndromes (see schema), as follows: (1) Silent carrier involves one deleted gene. These individuals have low-normal MCV or mild microcytosis (75 fL to 80 fL). (2) a-Thalassemia trait involves two deleted genes. These individuals have mild-to-moderate microcytosis (MCV <75>cis-form involves two deleted genes, ‘both on one allele’; this serious form is common in the Mediterranean population. The trans-form involves two deleted genes, ‘one on each allele’; this benign form is common in the Arabian Peninsula. (3) Hemoglobin H disease involves three deleted genes (one parent has cis-form a-thalassemia trait [heterozygous a0] and one has silent carrier). The unpaired b-chains form tetramers (b4), termed "hemoglobin H" (not to be confused with hemoglobin H disease). The b4 aggregates are more soluble than the a4 aggregates. Thus, patients with hemoglobin H disease usually have only moderate-to-severe hemolytic anemia. (4) Hydrous fetalis involves four deleted genes (both parents have ‘heterozygous a0’). The unpaired g-chains (g4, ‘Bart’s hemoglobin, a fast migrating variant’) have high affinity to oxygen (bind oxygen tightly and release almost none to the fetal tissue), leading to hypoxia and hydrops (edema due to heart failure).
Bart’s hemoglobin is elevated in all forms of a-thalassemia; it can be used to screen for neonatal a-thalassemia. Bart’s Hemoglobin constitutes 1% to 2% in silent carrier, 2% to 10% in trait, 20% to 30% in hemoglobin H disease, and >80% in hydrops fetalis. As noted above, newborns with a-thalassemia trait have MCV <94>
VI. Chronic transfusion
Complications of chronic transfusions include iron overload, alloimmunization, and viral infections. Accumulation of iron results in diabetes and hypopituitarism (hypogonadotropic hypogonadism, impaired fertility, osteopenia, and osteoporosis). Cardiomyopathy and arrhythmias are the leading causes to death. The same risk for hypogonadism exists with stem cell transplantation and is caused by previous iron overload and the conditioning regimen. One-third of females and two-thirds of males with thalassemia major fail to enter puberty after myeloablative treatment. Patients who are compliant with chelation have 50% chance of being alive at 30 y, whereas for noncompliant patients, this rate is 10%. Transmission of viral infections, especially HIV, hepatitis B, and hepatitis C remains an important complication.
Iron chelation is recommended for children >2 y after >10 transfusions, serum ferritin >1,000 µg/L (2,247 pmol/L), or liver iron ≥3 mg/g dry weight liver. The goals of chelation are liver iron 3 to 7 mg/g dry weight liver, ferritin 1,000 ng/mL (2,247 pmol/L), cardiac T2* >20 ms, and avoidance of organ dysfunction caused by iron overload. With aggressive chelation, iron-induced cardiotoxicity can be reversed and some endocrine complications may be improved. It is necessary to monitor for the adverse effects of chelation therapy with monthly liver and kidney function tests as well as annual audiologic and vision screening.
VII. Neonatal hematology
Hemoglobin F does not bind to 2,3-bisphosphoglycerate (2,3-BPG), accounting for its high oxygen affinity compared to hemoglobin A. This physical property allows hemoglobin F to bind more oxygen. Hemoglobin F is also more easily oxidized to methemoglobin (unable to bind oxygen as the iron in the heme is ferric [Fe3+] rather than ferrous [Fe2+]). Cells rich in hemoglobin F are larger and more resistant to osmotic stress than adult red cells. Thus, the diagnosis of hereditary spherocytosis utilizing osmotic fragility test should be delayed until after 6 mo.
Anemia of prematurity occurs in infants ≤32 weeks’ gestation. The hemoglobin reaches nadir at 4 to 8 weeks, as compared to the physiologic anemia of full-term newborns at 8 to 12 weeks. Its etiology includes low erythropoietin secretion and frequent phlebotomy. Prevention includes: (1) delayed cord clamping (30 to 60 sec), (2) reducing phlebotomy, (3) providing iron, and (4) increasing protein intake (3 to 4 g/kg/day).
Alloimmune hemolytic disease of the newborn (erythroblastosis fetalis) is a severe hemolysis caused by maternal anti-D (in Rh D negative mother) against D antigen (in Rh D positive fetus). Maternal anti-Kell is the second most common. Severity of the anti-Kell disease may progress quickly due to antibody-mediated suppression to erythropoiesis. Maternal antibodies against Duffy and the c and E antigens in the Rh group can also cause severe hemolysis. These infants are at risk for hyperbilirubinemia (kernicterus). Infants of these mothers may require an exchange transfusion if the bilirubin level is concerning. If the disorder is identified in utero, intrauterine transfusion may be utilized. IgG is not beneficial. Patients must be followed closely because anemia may be lasting. The primary approach to RhD incompatibility is
prevention; an RhD-negative mothers should receive one dose of anti-RhD at 28 weeks’ gestation and again postnatally. Hemolytic disease of the newborn caused by ABO incompatibility occurs exclusively in association with type ‘O’ mothers and type ‘A’ or ‘B’ mother; it is usually mild.
Hereditary spherocytosis {spherocytosis type 1; SPH1 (MIM#182900, AD); ANK1 (MIM#612641, ankyrin 1); SPH4 (MIM#612653, AD); SLC4A1 (MIM#109270, solute carrier family 4, anion exchanger, member 1)} is a heterogeneous defect in the red cell cytoskeleton, most commonly due to abnormal spectrin. It is sporadic in 10% of the cases. The defect results in membrane (surface) loss, causing sphere-shaped cells, increased fragility and premature trapping in the spleen. The presence of spherocytes on the blood smear establishes the diagnosis. Hemolysis may begin in the first 24 h of life, causing neonatal jaundice. Hypoplastic episodes (severe anemia and reticulocytopenia) due to a viral infection (e.g., B19 parvovirus) are common. Blood transfusion may be necessary during acute hemolytic or hypoplastic episodes. Splenectomy is necessary for persistent hemoglobin <100>10%. In neonates, eosin-5’-maleimide (EMA) is more reliable than peripheral smear (as neonatal erythrocyte morphology has significant variation) or osmotic fragility. Eosin-5’-maleimide binding is influenced by the MCV; thus, neonatal references (with a typical MCV of 105 fL) are needed to interpret the results. In a patient with a classic presentation and typical spherocytes on peripheral smear, particularly with a positive family history, no further diagnostic testing is required. Otherwise, a combination of eosin-5’-maleimide-binding and acidified glycerol reliably identifies hereditary spherocytosis, particularly in mild disease.
Hereditary elliptocytosis (HE) describes peculiar red cells with micropoikilocytes, elliptocytes, budding, and fragmentation. It is caused by pathogenic variants in the red cell membrane cytoskeletal proteins (e.g., α-spectrin, β-spectrin, protein 4.1R, glycophorin C). Its four types are: (1) Common HE; (2) Hemolytic HE; (3) Hereditary poikilocytosis/pyknocytosis (HPP); and (4) Spherocytic elliptocytosis (SE). Common HE (autosomal dominant) shows elliptocytes on blood smear in asymptomatic child (a mild hemolysis may occur with illnesses). Affected neonates may have severe hemolysis. Splenectomy may be required in HPP to improve the anemia; the MCV is typically very low (30 to 50 fL). SE is characterized by elliptocytes and microspherocytes (without poikilocytosis or fragments).
Neonatal alloimmune thrombocytopenia results from maternal antibodies against human platelet antigen (HPA, most commonly HPA-1a followed by HPA-5b and HPA-15b) that is present in the fetus and not in the mother. It can occur in the first pregnancy. The thrombocytopenia is often severe and may result in intracranial bleeding. Maternal platelet apheresis is effective. Other causes include maternal immune thrombocytopenia (ITP), asphyxia, pregnancy-induced hypertension, intrauterine growth retardation, viral infection (cytomegalovirus), sepsis, and trisomy 21.
About 10% of infants of mothers with ITP develop thrombocytopenia, which may occur after the mother’s platelet count is normalized. The clinical presentation is less severe than in ‘neonatal alloimmune thrombocytopenia’. The risk of intracranial hemorrhage is low and is not influenced by the mode of delivery. Platelet counts need to be checked from a cord blood sample and repeated every 2-3 days for the first week. Platelet counts usually reach a nadir in 2 to 5 days and recover by day 7; some infants remain thrombocytopenic for 3 mo. Cranial ultrasonography should be performed to assess intracranial hemorrhage. Infants with a platelet count of <50>
Newborns whose mothers have systemic lupus erythematosus (SLE) frequently develop skin lesions (erythematous, annular) and complete atrioventricular block. Mothers with Ro/SSA and La/SSB autoantibodies are more likely to have a newborn with lupus syndrome. The resulting anemia and thrombocytopenia respond to transfusion, corticosteroids and intravenous immunoglobulin. The neutropenia resolves by 6 mo [?].
Trisomy 21 is frequently associated with lymphopenia, abnormal thymus development and function, frequent respiratory infections, autoimmunity, and hematologic malignancy. The newborn screening for severe combined immune deficiency (SCID) is through identification of T-cell receptor excision circles (TREC).
Severe congenital neutropenia is a heterogeneous disorder associated with neutrophil counts <0>ELANE (elastase, neutrophil-expressed, MIM#130130) variants are seen in both severe congenital neutropenia (MIM#202700, autosomal dominant) and cyclic neutropenia (MIM#162800, autosomal dominant). Shwachman syndrome (gene: ribosome maturation factor, SBDS, MIM#607444; phenotype: MIM#260400, autosomal recessive) is associated with pancreatic malabsorption, bell-shaped chest, metaphyseal dysplasia, and waxing and waning neutropenia.
Neonatal alloimmune neutropenia occurs with maternal sensitization to fetal neutrophils bearing paternal antigens; more common in multiparous mothers. It may last up to 6 mo. The bone marrow shows myeloid hyperplasia. The antibody is identified in the serum of the mother and the infant, and is against the HNA-1 neutrophil FCγ receptor IIIb.
Benign (ethnic, familial) neutropenia is mild and associated with African, Yemenite, West Indian, and Arab ancestries. It is linked to variants in ACKR1 (atypical chemokine receptor 1; MIM#613665); previously termed: Duffy antigen receptor for chemokines (DARC).
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I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.
We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.
I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.
I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.
I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.
Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.
“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.
Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.
The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.
Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.
Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.
Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”
Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner
My Testimonial Covering as fellowing: Lin-Show Chin. The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews.
My experience publishing in Psychology and Mental Health Care was exceptional. The peer review process was rigorous and constructive, with reviewers providing valuable insights that helped enhance the quality of our work. The editorial team was highly supportive and responsive, making the submission process smooth and efficient. The journal's commitment to high standards and academic rigor makes it a respected platform for quality research. I am grateful for the opportunity to publish in such a reputable journal.
My experience publishing in International Journal of Clinical Case Reports and Reviews was exceptional. I Come forth to Provide a Testimonial Covering the Peer Review Process and the editorial office for the Professional and Impartial Evaluation of the Manuscript.
