Factors Related to the Quality of Life in Children with Transfusion-Dependent Thalassemia.

Objective: Increased survival rate of patients with Transfusion-dependent Thalassemia (TDT) should be in line with their good quality of life (QoL). The study aimed to analyze the relationship between sociodemographic factors and clinical characteristics with the QoL of children with TDT. Methods: A cross-sectional study was conducted at Hasan Sadikin General Hospital from December 2022 to February 2023. A total of 158 eligible subjects aged 5-18 years with TDT were included in the analysis. QoL assessment was performed using child self-report and parent-proxy report questionnaires, along with physical examination findings. Bivariate and multivariate analyses were conducted to analyze the data. Results: A total of 158 subjects who met the research criteria were included in the analysis. Of 58.9% of children with TDT had a low adherence rate to iron chelating therapy (ICT). School function had the lowest score in QoL based on child-self report and parent proxy. Gender (p<0,05) and adherence to ICT (p<0,05) were significantly associated with lower quality of life. Conclusion: Female and adherence to ICT were predictors of children with TDT's QoL.

Survival and Treatment Outcomes of Childhood Acute Lymphoblastic Leukemia in a Low-Middle Income Country: A Single-Center Experience in West Java, Indonesia.

Purpose: This study aimed to determine the survival rates and treatment outcomes of patients with childhood Acute Lymphoblastic Leukemia (ALL) in a single-center study at Indonesia. Patients and Methods: Factors contributing to the relapse and survival of ALL in Bandung, Indonesia, were evaluated. Data were collected from the medical record and the Indonesian Pediatric Cancer Registry (IPCAR). Subsequently, univariate and multivariate analyses were evaluated using Cox proportional hazard regression and Kaplan Meier was used for survival analysis. An analytic observational study was conducted on newly diagnosed children aged 1-18 with ALL from January 2019 to December 2022. Results: A total of 137 children were included in the analysis, 30 (21,9%) were dropped out during treatment and 60.5% died during the study period. Most of the deaths occurred after relapse in 32 (38.5%) with a high early relapse (70.5%), occurring mainly during the maintenance phase (42.4%). At the one-year mark, the observed overall survival (OS) rate was at 36%, while event-free survival (EFS) was lower, at 19%. Univariate Cox regression analysis showed that the leucocyte counts at diagnosis (p=0.005) and response to induction phase (p < 0.008) was associated with the death of ALL. Furthermore, a response to induction phase was significant [hazard ratio 4.67 (CI 95%: 1.64-13.29); p = 0.004] in the multivariate analysis. Conclusion: In conclusion, this study underscored the persistent challenges of high treatment discontinuation rates and the occurrence of very early relapses in low- to middle-income countries (LMICs), which significantly impacted the OS of children diagnosed with ALL.

Allergic Reactions to E. coli Asparaginase are Associated with Decreased Asparaginase Activity in an Indonesian Pediatric Population with ALL.

PURPOSE: The asparaginase's (ASP) utility for ALL treatment is limited by neutralizing antibodies, which is problematic in countries whose access limited to alternative preparations. ASP antibody levels and activity was measured during remission induction and associated with allergy manifestations. METHODS: E. coli ASP was dosed at 7500 IU/m2. ASP IgG antibody levels were quantified at the beginning and end of induction. ASP activity was measured 24 hours after 1st and 5th dose (standard-risk) or 7th dose (high-risk patients) administration, and within 24 hours in case of allergic reactions. Allergy was monitored by CTCAE version 3. Parametric and non-parametric was performed for data analysis. RESULTS: ASP antibody and activity levels were available in 41/63 consecutive patients. Allergic manifestations occurred in 13/41, with urticaria being the most frequent. There were no significant differences in subject characteristics based on allergic reactions. The 5th dose was the most frequent time of onset. Antibody levels in allergy group at the end of induction did not differ from those at baseline (p<0.05). Using a 24-hour level of 100 mU/mL as a threshold for adequate ASP activity, 6/13 patients with allergy had adequate levels compared to 26/28 patients without (p<0.05). The ASP activity level at the end of induction phase in both groups did not show a significant decrement. CONCLUSION: The E. coli ASP activity with adequate levels were significantly higher in non-allergy group. Its activity level was not accompanied by increment of IgG in allergic group indicates other factors might affect activity levels in allergy group.

Type of cancer and complementary and alternative medicine are determinant factors for the patient delay experienced by children with cancer: A study in West Java, Indonesia.

INTRODUCTION: Most pediatric cancer patients in developing countries present at an advanced stage due to delayed diagnosis, being an important barrier to effective care. The objective of this study was to evaluate the associated factor of patient delay and explore significant parental practice-associated risk factor to patient delay. METHODS: This was a sequential mixed methodology, utilizing data from the Indonesian Pediatric Cancer Registry for clinical variables and completed interviews with parents using structured questionnaires to obtain their sociodemographic data. A binary logistic regression analysis model was fitted to identify factors associated with patient delay. Additional semi-structured interviews related to parental practice of using complementary and alternative medicine (CAM) were administered to 30 parents. Thematic framework analysis was performed on qualitative data to explore determinant factors of parental practice of using CAM. RESULTS: We interviewed 356 parents with children with cancer. The median patient delay was 14 days (interquartile range [IQR]: 6-46.5 days). The most extended delay was in patients with malignant bone tumors (median 66, IQR: 14-126). In multivariable logistic regression analysis, solid cancer (odds ratio [OR] = 5.22, 95% confidence interval [CI]: 2.79-9.77, p < .001) and use of CAM (OR = 1.86, 95% CI: 1.13-3.08, p = .015) were associated with patient delay. Qualitative interviews highlighted key issues relative to determinant parental factors using CAM, including vague initial childhood cancer symptoms, parental health-seeking behavior, CAM availability and accessibility, also barriers of healthcare facilities. CONCLUSION: Type of cancer and use of CAM are essential factors that cause patient delay. It should be addressed in the future childhood cancer awareness and childhood cancer diagnosis pathway.

FVIII inhibitor surveillance in children with hemophilia A in Indonesia: a report from the Indonesian Pediatric Hematology-Oncology Working Group.

Background: Factor VIII (FVIII) inhibitor diagnosis and surveillance in Indonesia are challenging owing to geographic conditions and the lack of laboratory facilities nationwide for inhibitor assays. This study aimed to determine the prevalence of FVIII inhibitors in children diagnosed with hemophilia A (HA) in Indonesia. Methods: A cross-sectional study was conducted in 12 hospitals in eight provinces of Indonesia between 2020 and 2021. Factor VIII inhibitor screening was performed in a central hemostasis laboratory for all children with HA (≤18 yr) who had received a minimum of 10 exposure days to clotting factor concentrates. The FVIII inhibitor titer was determined using the Bethesda assay. Results: Children (388) were enrolled in this study, including 219 (56.4%), 131 (33.8%), and 38 (9.4%) with severe, moderate, and mild HA, respectively. The prevalence of children who developed FVIII inhibitors was 37 out of 388 (9.6%). Factor VIII inhibitors were found in 25/219 (11.4%) severe, 11/131 (8.3%) moderate, and 1/38 (2.6%) children with mild HA. Thirteen children had low-titer inhibitors and 24 had high-titer inhibitors, with a median of 9.44 (1.48‒412.0) Bethesda Units. Among 13 children with low-titer inhibitors, eight underwent a confirmation test, of which five tested negative and were classified as transient. A significant difference in annual joint bleeding rate was found between patients with low and high inhibitor titers and those without inhibitors (P＜0.001). Conclusion: Factor VIII inhibitor prevalence in Indonesia was relatively low. However, the risk factors that may contribute to FVIII inhibitor development among Indonesian patients require further study.

Parental Factors Contribute to Childhood Cancer Abandonment Treatment During COVID-19.

Factors influence a person's health seeking behavior related to abandonment rate on pediatric oncology treatment during this pandemic is unknown. The aim is to identify factors influencing abandonment rates in early pandemic. This was a cross-sectional studies during early pandemic and analyze factors in parents whose children had treatment for malignancy contribute to their children's abandonment treatment rate through guided interview using questionnaire. The characteristic related significantly with treatment abandonment is maternal education. It is found that patients whose mother had education less than secondary school was 1.315 (CI 1.013-1.707) having risk experience abandonment treatment. Parental perception related to impact of COVID-19 was significantly related to treatment abandonment rate with RR 0.202 (CI 0.86-0.471). Patients whose parents have positive perception how abandonment treatment affect their child outcome, believe that doctor has taken step to prevent COVID-19 transmission during treatment, and receive information about COVID-19, having less risk being abandonment treatment.

The incidence and mortality of childhood acute lymphoblastic leukemia in Indonesia: A systematic review and meta-analysis.

BACKGROUND: The incidence of childhood ALL in Indonesia is still largely unknown. The widely mentioned statistics from other countries turn out to be only estimated figures. Other data do not specify the types of leukemia and are not specifically focused on children. Therefore, this study aims to pool incidence and mortality statistics from available studies in Indonesia. METHODS: We searched five different academic databases, including Pubmed, MEDLINE, Cochrane Library, Science Direct, and Google Scholar. Three Indonesian databases, such as the Indonesian Scientific Journal Database (ISJD), Neliti, and Indonesia One Search, were also utilized. Incidence was expressed as per 100,000 children. We used the Newcastle-Ottawa scale (NOS) to assess the quality of cohort studies. The inclusion criteria are cohort studies published in the languages of English or Indonesian. For this analysis, we define children as 0-18 years old. FINDINGS: The incidence rate for childhood ALL was found to be 4.32 per 100,000 children (95% CI 2.65-5.99) with a prediction interval of 1.98 to 9.42 per 100,000 children. The incidence rate is higher in males, with 2.45 per 100,000 children (95% CI 1.98-2.91) and a prediction interval of 1.90 to 3.16 per 100,000 children. As for females, the incidence rate is 2.05 per 100,000 children (95% CI 1.52-2.77) with a prediction interval of 1.52 to 2.77 per 100,000 children. The mortality of childhood ALL ranges from 0.44 to 5.3 deaths per 100,000 children, while the CFR is 3.58% with varying true effect sizes of 2.84% to 4.52%. INTERPRETATION: With 79.5 million children living in Indonesia in 2018, this means that there were roughly 3,434 new cases of childhood ALL. An organized effort between multiple sectors is needed to improve the registries of childhood ALL in Indonesia.

Extended family thalassemia screening as a feasible alternative method to be implemented in identifying carriers in West Java, Indonesia.

The thalassemia screening program in Indonesia mostly conducted sporadically. Ideal prospective screening is still limited. This study aimed to compare thalassemia screening methods using the extended family approach with and without a history of severe thalassemia and the feasibility of implementing extended family screening method. A case control study was conducted in Dr. Hasan Sadikin General Hospital Bandung with 3 generations of extended families. Data were collected from 150 subjects of 8 extended families with severe thalassemia as an index case entry and 151 subjects of 12 families with no history of thalassemia. All subjects were examined for Hb, MCV, MCH, and peripheral blood smear (PBS) as initial laboratory examinations. Subjects with MCV < 80 fL, MCH < 27 pg, and suggestive findings on PBS continued hemoglobin analysis. Carrier status was determined by definition. All subjects consented to undergo screening and voluntarily participated. The proportion of thalassemia carriers and the participation rate between the 2 groups were compared. Sixty-four of 150 (42.7%) and 16 of 151 (10.6%) carriers were identified in both the case and control group (p < 0.001). The participation rate was 42-88 vs. 23-100% (p = 0.244). The mean age was 31.9 ± 21.2 vs. 31.1 ± 20.8 years (p = 0.782). The median family size was 28.5 vs. 20 subjects per family (p = 0.245). The types of identified thalassemia carrier in both groups consisted of ß-thalassemia, ß-thalassemia/HbE, suspected α-thalassemia, and ß-thalassemia Hb variant. All carriers continued the counseling process. The extended family method seems feasible to be implemented for thalassemia screening in West Java, Indonesia.

Serum TNF-α Level as a Possible Predictor of Inhibitor Levels in Severe Hemophilia A.

BACKGROUND: The development of factor VIII (FVIII) inhibitor in patients with hemophilia A (PWHA) is a great challenge for hemophilia care. Both genetic and environmental factors led to complications in PWHA. The development of inhibitory antibodies is usually induced by the immune response. Tumor necrosis factor α (TNF-α), one of the cytokines, might contribute to its polymorphism. In this study, we investigated the clinical factors, level of serum TNF-α, and polymorphism of c.-308G > A TNF - α gene in inhibitor development in severe PWHA. METHODS: A cross-sectional study was conducted among all PWHA in West Java province. The clinical parameters, FVIII, FVIII inhibitor, and serum TNF-α level were assessed. The genotyping of -380G > A TNF-α gene polymorphism was performed using polymerase chain reaction and Sanger sequencing. RESULTS: Among the 258 PWHA, 216 (83.7%) were identified as severe PWHA. The FVIII inhibitor was identified in 90/216 (41.6%) of severe PWHA, consisting of 45 high-titer inhibitors (HTI) and 45 low-titer inhibitors (LTI). There was a significant correlation between serum TNF-α level and the development of HTI (p = 0.043). The cutoff point of serum TNF-α level, which can be used to differentiate between HTI and LTI, was 11.45 pg/mL. The frequency of FVIII replacement therapy was significant only in HTI of severe PWHA regarding serum TNF-α level (p = 0.028). There is no correlation between polymorphisms of -380G > A TNF-α gene and inhibitor development (p = 0.645). CONCLUSIONS: The prevalence of FVIII inhibitor in severe PWHA in West Java, Indonesia, was 41.6%. The frequency of replacement therapy is a risk factor for inhibitor development. Serum TNF-α level might be used to differentiate between high and low inhibitor levels in severe hemophilia A, and this might support decision making regarding treatment options for inhibitor in severe hemophilia A.

Monitoring Of High-Dose Methotrexate (Mtx)-Related Toxicity and Mtx Levels in Children with Acute Lymphoblastic Leukemia: A Pilot-Study in Indonesia.

The administration of high-dose methotrexate (HD-MTX) requires an accurate monitoring of blood MTX levels to determine the regimen of leucovorin rescue and urine alkalinization to prevent toxicity. However, it is technically and logistically challenging to screen patients routinely in limited-resource settings. This study aimed to evaluate blood MTX levels at 24- and 48-hours from start of infusion in relation to clinical toxicity in childhood ALL. METHODS: A prospective cohort study was conducted on 32 consecutive children with acute lymphoblastic leukemia (ALL) who had received at least one cycle of 1 g/m2 HD-MTX intravenous infusion as a part of consolidation treatment based on the 2013 Indonesian ALL Protocol. In total, 68 cycles were evaluated. Serum MTX concentrations were measured using enzyme immunoassay. MTX toxicity was categorized using common toxicity criteria (CTCAE) 3.0 version. The association between MTX level and clinical toxicity was assessed by non-parametric analysis. RESULTS: The 24-hours MTX level was median 29.8 ng/mL (0.065 µmol/L) (IQR 8.1-390.6) with a modest decrease in 48-hours MTX serum level in all cycles (median 28.3 ng/mL and 0.062 µmol/L; IQR 0.35-28.7; p <0.05). The two most common toxicities were hepatotoxicity (32.2%) and neutropenia (30.9%). Nephrotoxicity and febrile neutropenia occurred in 8.8% and 5.8% of patients, respectively, with low percentage of mucositis (4.3%) and thrombocytopenia (5.6%) recorded.  No statistically significant association was found between MTX levels and clinical toxicity, except for liver toxicity. CONCLUSION: Serum MTX levels at 24-hours and 48-hours are low, followed by only 4.4% grade III/IV hepatotoxicity and 26,4% grade III/IV neutropenia. There is no significant association between the clinical toxicity and MTX levels at the two points of measurement. An attempt to increase the MTX dose and/or to introduce a loading dose should be considered in subsequent ALL protocol as supported by further pharmacokinetic MTX studies in the Indonesian population.

Iron Status in Newly Diagnosed ß-Thalassemia Major: High Rate of Iron Status due to Erythropoiesis Drive.

BACKGROUND: Iron overload in severe ß-thalassemia is a serious complication that occurs during the course of the disease. Information about the iron status during initial illness with ß-thalassemia major seemed to be limited. This study is aimed at analyzing iron status, serum hepcidin, and growth differentiation factor 15 (GDF15) levels in newly diagnosed ß-thalassemia major. METHODS: A case-control study was performed at Dr. Hasan Sadikin General Hospital, which included 41 children with newly diagnosed ß-thalassemia major. Age- and sex-matched controls were enrolled. The subjects had no blood transfusion, had normal liver function, and had no sign of inflammation. The groups were compared in terms of the levels of hemoglobin (Hb), serum ferritin (SF), transferrin saturation (TS), serum hepcidin, and GDF15 as iron homeostasis parameters. RESULTS: Of the 41 newly diagnosed ß-thalassemia major patients, those who were less than 24 months old had significantly lower median Hb levels than controls (5.0 vs. 11.7 g/dL, P < 0.001). The median SF and TS levels were significantly higher than those in controls (315.0 vs. 29.0 ng/mL, P < 0.001; 70.6 vs. 16.5%, P < 0.001), and median hepcidin was at the normal limit, but the value was higher in patients (251.0 vs. 123.1 ng/mL, P < 0.001). The median GDF15 level was significantly higher in patients (2,095.3 vs. 342.4 pg/mL, P < 0.001). There was a positive correlation between SF-TS, SF-hepcidin, TS-hepcidin, SF-GDF15, TS-GDF15, and hepcidin-GDF15 (P < 0.001). CONCLUSION: In newly diagnosed ß-thalassemia major, an increase in iron status occurred. This may be caused by increased iron absorption due to massive erythropoietic activity, characterized by an increase in GDF15 levels, which does not cause hepcidin suppression. The iron homeostasis response seems to be physiologically indicated by a tendency to increase hepcidin levels.

Temporal association between serious bleeding and immunization: vitamin K deficiency as main causative factor.

BACKGROUND: Bleeding as an adverse event following immunization (AEFI) that is rarely reported in children, although it can be a parental concern. Bleeding episodes ranging in severity from mild to severe and defined as any external and/or internal bleeding can be caused by acquired or hereditary disorders. This study analyzes whether bleeding episodes in children that were recorded as AEFIs are causally associated with immunization and elaborates their etiology. METHODS: A cross-sectional study of 388 AEFI cases in children from West Java Provincial Committee in Indonesia confirmed by case findings from 2000 until 2017. RESULTS: Of the total number of cases studied, 55 (14%) involved children aged 5 days to 12 years who presented with bleeding and were referred to a provincial hospital. Analysis revealed that 32 cases were most likely caused by acquired prothrombin complex deficiency (APCD) and 30 of these APCD cases were strongly suspected to be manifestations of vitamin K deficiency bleeding (VKDB). All VKDB subjects were aged 5 days to 3 months without a history of administration of prophylactic vitamin K. When a World Health Organization classification was used, most bleeding cases in this study became coincidental events with a temporal association with immunization. A causality assessment suggested that these cases were causally unrelated. CONCLUSION: Most cases of bleeding reported as an AEFI were found to be VKDB, which is considered a coincidental event following immunization with a temporal association, and an unrelated category based on the results of a causality assessment. Vitamin K should be administered to all newborns as a prophylactic and AEFI surveillance should be improved based on the low numbers of AEFI reported in Indonesia.

Time to Start Delivering Iron Chelation Therapy in Newly Diagnosed Severe ß-Thalassemia.

BACKGROUND: Iron overload is still a major complication of severe ß-thalassemia. Indication to start iron chelation therapy is based on serum ferritin (SF) or transferrin saturation (TS) level or the amount of transfusion. The goal of this study is to analyse the pattern of iron status, the amount of transfusion regarding the time to start iron chelator, and serum hepcidin levels in newly diagnosed severe ß-thalassemia. METHODS: A prospective cohort study was performed at Hasan Sadikin General Hospital on newly diagnosed severe ß-thalassemia patients. Subjects had not received any blood transfusion with normal liver function test, CRP, and IL-6 levels who consumed normal diet according to age. The SF and TS levels indicate iron status, while hepcidin level indicates iron regulator status. Main indicator to start iron chelation therapy when SF level ≥1.000 ng/mL, TS level ≥70%, or after receiving transfusion at least 10 times. Statistical analysis used Mann-Whitney and Spearman. RESULTS: Forty-two newly severe ß-thalassemia, 30 (71.4%), were diagnosed before 1 year old, mean 9.9 ± 6.4 months, range 2-24 months. Range amount of transfusion until SF level reached ≥1,000 ng/mL were 4-12 times, mean 7 ± 2 times. Mean SF and TS level at diagnosis were 365.6 ± 194.9 ng/mL and 67.3 ± 22.5%, while hepcidin level was normal, mean 242.6 ± 58 ng/mL. 36/42 patients have reached SF >1000 ng/mL with amount of transfusion less than 10 times. There was no significant difference of SF, TS, and hepcidin levels when SF >1000 ng/mL in the group with amount of transfusion 7-12 and less than 7 (p = 0.454, p = 0.084, p = 0.765), respectively. A significant positive correlation between SF and amount of transfusion was observed (p < 0.001; r = 0.781). CONCLUSION: Iron overload in severe ß-thalassemia patients might occur earlier even before they received 10 times transfusion. Hepcidin serum level tends to increase when iron overload just started.

The effect of the chitosan-collagen membrane on wound healing process in rat mandibular defect.

BACKGROUND: Collagen and chitosan are potential biomaterials for medical applications; chitosan-collagen membranes are used as a barrier membrane in guided tissue regeneration and guided bone regeneration. AIMS: The purpose of this study was to analyze the effect of the chitosan-collagen membrane on wound healing in rat mandibular defect by counting the number of fibroblasts and new blood vessels. MATERIALS AND METHODS: As much as 24 male Wistar rats were divided into two groups, the treatment and control group. Bone defects were made In the rat mandible with diamond bur with a diameter of 2 mm, then the defect was covered with a chitosan-collagen membrane, and the control group was covered without application of chitosan-collagen membrane. After the 3rd, 7th, 14th, and the 21st day, the defect site was analyzed histologically. The number of fibroblasts and blood vessels was counted under a light microscope, at five fields with ×1000 and ×400 microscope magnification. STATISTICAL ANALYSIS USED: This study was done by using analysis of variance and unpaired t-test. RESULTS: The average number of fibroblasts and blood vessels in the treatment group was higher than the control group. There was a significant difference in the number of fibroblasts on the 3rd and 7th day (P = 0.001; P = 0.001) and the number of blood vessels on the 3rd day (P = 0.04). CONCLUSION: The chitosan-collagen membrane was able to increase the number of fibroblasts and new blood vessels in the wound healing process.

Mutation spectrum of ß-globin gene in thalassemia patients at Hasan Sadikin Hospital - West Java Indonesia.

Thalassemia is the most common hereditary haemolytic anemia in Southeast Asia, in which Indonesia is among countries that are at a high risk for thalassemia. It has been reported that mutation in the beta-globin gene is responsible in severe Thalassemia. However, the spectrum of beta-globin gene mutations in Indonesian population varies in different regions . Thus, this study aimed to identify the most prevalent mutation of Thalassemia patients from the Hasan Sadikin Hospital, Bandung, using this as a reference hospital for Thalassemia in West Java. The three most prevalent mutations of beta globin (IVS1nt5, Cd26 (HbE), and IVS1nt1), were conducted in the beginning of this study. Mutations of 291 samples were detected by PCR-RFLP in the Molecular Genetic Laboratory, Faculty of Medicine Universitas Padjadjaran, Bandung. The prevalence of the beta globin gene mutation types were 47.4% IVS1nt5 homozygote, 9.9% compound heterozygote IVS1nt5/HbE, 5.4% compound heterozygote IVS1nt5/IVS1nt1, 1.4% compound heterozygote HbE/IVS1nt1, 1% HbE homozygote, 14.4% Compound heterzygote IVS1nt5/… (no paired mutation), 2.06% compound heterozygote HbE/… (no paired mutation), 1.3% compound heterozygote IVS1nt1/… (no paired mutation), and 7 samples were unidentified. The thalassemia mutation IVS1nt5 homozygote is the most common mutation found in Thalassemia patients at Hasan Sadikin Hospital, Bandung. The samples with unidentified results might carry mutations other than the three that are observed in the present study.

Severe α-thalassemia intermedia due to a compound heterozygosity for the highly unstable Hb Adana (HBA2: c.179G>A) and a novel codon 24 (HBA2: c.75T>A) mutation.

We report a novel mutation at codon 24 of the α2-globin gene (HBA2: c.75T > A) found in a Sundanese family. This novel mutation was detected during prenatal diagnosis. The couple already had a 7-year-old boy who exhibited clinically severe α-thalassemia intermedia (α-TI), and he was found to be a compound heterozygote for the novel mutation at codon 24 and the previously described Hb Adana (HBA2: c.179G > A) at codon 59 of the α2-globin gene. The father was a carrier of the novel point mutation and showed normal hemoglobin (Hb) and a low mean corpuscular volume (MCV) and mean corpuscular Hb (MCH) value.