Clinical and etiological profile of anemia in a clinical hematology department of North Africa : A cross-sectional study.

Wiem Boufrikha: Conceptualization, Data curation, Validation, Visualization, Writing – original draft. Sirine Ben Salem: Conceptualization, Data curation, Investigation, Methodology, Writing – original draft. Nourhene Mazhoud: Investigation, Methodology, Validation. Arwa Guedich: Validation, Writing – review & editing. Nader Slama: Validation, Writing – review & editing. Sarra Boukhris: Supervision, Validation, Writing – review & editing. Mohamed Adnene Lattiri: Supervision, Validation.

This descriptive study was conducted in 2022 in the Clinical Hematology Department of Fattouma Bourguiba University Hospital, Monastir. All patients presenting with anemia, isolated or associated with other abnormalities on the initial complete blood count (CBC), were included. Patients with incomplete records or lost to follow-up after the first consultation were excluded. Anemia was defined as (Hb) <13 g/dL in men and <12 g/dL in women [ 5 ], and severe anemia as hemoglobin <8 g/dL. Anemia was classified according to mean corpuscular volume (MCV) into microcytic (100 fL), and considered regenerative when the reticulocyte count exceeded 120,000/mm³ [ 5 , 6 ]. Peripheral blood smear (PBS) examination (May–Grünwald–Giemsa staining) was systematically performed to assess cell morphology and orient etiological diagnosis. In microcytic anemia, serum ferritin was measured and hemoglobin electrophoresis was performed when thalassemia was suspected. Normocytic anemia was evaluated by reticulocyte count, with hemolysis defined by elevated unconjugated bilirubin, increased lactate dehydrogenase, and decreased haptoglobin. Macrocytic anemia prompted assessment of vitamin B12 and folate levels, as well as evaluation for hepatic, endocrine, toxic, or drug-related causes. Bone marrow aspiration (BMA) and, when indicated, biopsy (BMB) were performed in cases of unexplained non-regenerative anemia. Additional investigations included inflammatory markers, immunological tests, thyroid function, direct Coombs test, and esophagogastroduodenoscopy (EGD) when appropriate. Data were analyzed descriptively using SPSS 26.0.

We included 296 patients in our study. The mean age of the study population was 47± 21 years, ranging from 3 to 102 years. A total of 62.5 % of patients were aged ≥40 years with a predominance in the 40–60-year age group. There was a female predominance (sex ratio= 0.38). Anemic syndrome was the most common circumstances of discovery (CD) (68 %). Asthenia (79/296; 26.7 %) and dizziness (55/296; 18.6 %) were the most frequently reported functional signs. Pallor was the most common clinical sign found in our study (90/296; 30.4 %). Biologically, the mean Hb level was 7.9 ± 1.9 g/dl (2.7 g/dl to 11.8 g/dl). Severe anemia was observed in 49.7 % of cases. Hypochromic microcytic anemia accounted for 55.7 % of cases. Regenerative anemia was observed in only 3 patients ( Table 1 ). BMA was performed in 68 patients while BMB was performed in only 9 patients. At the end of the etiological assessment, iron deficiency anemia (IDA) was the most frequent etiology, accounting for 165 cases (55.7 %), followed by other etiologies in decreasing order of frequency: megaloblastic anemia (39 cases, 13 %), MDS (32 cases, 11 %), MM (17 cases, 5.7 %), and AL (11 cases, 3.7 %) ( Fig. 1 ). Table 1 Detailed characteristics by parameter across anemia etiologies. Table 1: dummy alt text Parameter Total N = 296 ( %) IDA N = 165 ( %) Megaloblastic anemia N = 39 ( %) MDS N = 32 ( %) Multiple Myeloma N = 17 ( %) Acute Leukemia N = 11 ( %) Mean age (years) 47 (3–102) 38.8 (12–102) 62.7 (29–90) 67.7 (15–93) 64.8 (51 – 84) 36.7 (3–69) Female n ( %) 214 (72.3) 142 (86) 23 (59.0) 14 (43.8) 8 (47.1) 9 (81.8) Sex ratio (M/F) 0.38 0.16 0.7 1.28 0.88 0.22 Main circumstance of discovery Anemic syndrome (68 %) Anemic syndrome Anemic syndrome (100 %) Anemic syndrome (50 %) Bone pain (58.8 %) Tumoral syndrome Main clinical signs Pallor (30.4 %) Asthenia (32 %) Pallor (28 %) Digestive signs (38.4 %) Pallor (25 %) Pallor (41.2 %) Tumoral syndrome (36.3) Mean Hb level 7.9 d/dl (2.7–11.8) 7.8 g /dl (2.7 – 11.4) 7.6 g/dl (3.7 −11.8) 7.8 g /dl (3.8 – 10.8) 8.8 g /dl (3.6 – 11.8) 8.2 g /dl (5.9 – 10.8) Anemia type • Microcytic 165 (55.7) 149 (90.3) 3 (7.7) 2 (6.3) 1 (6) 2 (18.2) • Normocytic 98 (33.3) 16 (9.7) 11 (28.3) 27 (84.4) 15 (88) 9 (81.8) • Macrocytic 33 (11)) - 25 (64) 3 (9.4) 1 (6) - Isolated anemia 200 (67.6) 143 (86.7) 14 (36) 14 (43.8) 12 (70.6) 2 (18.2) Severe anemia 147 (49.7) 85 (51.5) 23 (59) 18 (56.2) 3 (17.6) 5 (45.4) Associated cytopenias All Rare Pancytopenia (38.4 %)/Bicytopenia (25.6 %) Bi- (40.6 %) / Pancytopenia (15.6 %) Thrombocytopenia (17.7 %) Frequent Key diagnostic features - Low ferritin level Vit B12 ↓ / Folate ↓ Bone marrow dysplasia Plasma cell disorder Blasts >20 % *IDA: Iron deficiency anemia; Hb: Hemoglobin; MDS: Myelodysplastic syndrome. Fig. 1 Different Etiologies of Anemia *Others : hypothyroidism, renal failure, parvovirus B19 infection, hypersplenism, and drug toxicity. Fig 1: dummy alt text Detailed characteristics by parameter across anemia etiologies. Microcytic Normocytic Macrocytic *IDA: Iron deficiency anemia; Hb: Hemoglobin; MDS: Myelodysplastic syndrome. Different Etiologies of Anemia *Others : hypothyroidism, renal failure, parvovirus B19 infection, hypersplenism, and drug toxicity. We will now present a detailed analysis of the most frequently identified etiologies in our study, focusing on IDA, megaloblastic anemia, and the most prevalent malignant hematological disorders observed. IDA was diagnosed in 165 patients (55.7 % of all cases). The mean age in this group was 38.8 ± 17.2 years, ranging from 12 to 102 years. Women were the most affected (86 %) with a sex ratio of 0.16. Fig. 2 shows a female predominance across all age groups, except in the elderly, where a male predominance was observed. Ferritin levels were measured in 82 patients, of whom 72 (87.8 %) had low levels, representing 49.6 % of the total sample ( Table 1 ). The remaining 10 patients had normal ferritin levels due to prior iron supplementation at first consultation, while those without ferritin testing had been previously diagnosed with IDA and referred for further management. After completion of the biological workup and the indicated investigations, gastrointestinal and gynecological etiologies were identified in 13.3 % and 4.2 % of cases, respectively, while undetermined causes of IDA accounted for 82.5 % of cases ( Table 2 ) Fig. 2 Distribution of Iron-Deficiency anemias according to age groups and sex. Fig 2: dummy alt text Table 2 Etiological profile of iron deficiency anemia. Table 2: dummy alt text Etiology Number n ( %) Gastrointestinal cause 22/165 (13.3) • Gastritis 10(45.5) • Hemorrhoids 4(18.2) • Peptic ulcer disease 3(13.6) • Peptic esophagitis 2(9) • Celiac disease 1(4.5) • Malabsorption (gastrectomy) 1(4.5) • Gastric tumor 1(4.5) Gynecologic causes 7/165 (4.2) • Uterine fibroid 4(57.1) • Functional metrorrhagia 1(14.3) • Ovarian cyst 1(14.3) • Adenomyosis 1(14.3) Undetermined cause 136/165 (82.5) Distribution of Iron-Deficiency anemias according to age groups and sex. Etiological profile of iron deficiency anemia. Gastritis Hemorrhoids Peptic ulcer disease Peptic esophagitis Celiac disease Malabsorption (gastrectomy) Gastric tumor Uterine fibroid Functional metrorrhagia Ovarian cyst Adenomyosis Vitamin deficiency was observed in 39 patients (13.2 %). The mean age in this group was 62.7 ± 17.3 years (29–90 years), with a sex ratio of 0.7. Anemic syndrome was present in all patients. Digestive symptoms were observed in 15 patients (38.5 %). The mean Hb level was 7.6 ± 2.3 g/dL (range: 3.7–11.8 g/dL). Macrocytosis was noted in 64 % of cases, and pancytopenia in 38.4 % ( Table 1 ). PBS showed anisocytosis in 33 % of cases and neutrophil hypersegmentation in 23 %. Vitamin levels were measured in 29 patients, confirming vitamin B12 deficiency in 23 (59 %) and folate deficiency in 6 (15.3 %). Vitamin testing was not performed in 10 patients, mainly elderly individuals with clinical and laboratory features strongly suggestive of megaloblastic anemia. EGD was performed in 3 patients, revealing gastric mucosal atrophy in 2 cases and Helicobacter pylori gastritis in 1 case; the other patients refused endoscopic evaluation. Anti-intrinsic factor and anti-parietal cell antibodies were tested in 20 patients (51.2 %), among whom Biermer’s anemia was diagnosed in 13 (33.3 %). Table 3 summarizes the different etiologies of megaloblastic anemia. Table 3 Etiological profile of megaloblastic anemia. Table 3: dummy alt text Etiology Number n( %) Vitamin B12 deficiency 23/29(79.3) • Pernicious anemia 13(56.5) • Non-Pernicious anemia 10(43.5) *Nutritional deficiency 3(13) *Malabsorption * Undetermined cause 3(13) 4(17.4) Folate deficiency 6/29(20.7) Etiological profile of megaloblastic anemia. Pernicious anemia Non-Pernicious anemia MDS was diagnosed in 32 patients, representing 10.8 % of the study population. The mean age in this group was 67.7 ± 17.5 years (15–93 years). A slight male predominance was noted. Three patients had a history of neoplasia treated with chemotherapy. Anemic syndrome was the most frequent CD (50 %), followed by incidental detection of anemia during an annual check-up for a chronic condition. Anemia was isolated in 43.8 % of cases and was predominantly normocytic (84.4 %). Bicytopenia and pancytopenia were observed in 40.6 % and 15.6 % of cases, respectively ( Table 1 ). MM was diagnosed in 17 patients (5.8 %). The mean age in this group was 64.8 ± 10 years, with a sex ratio of 0.88. The most common CD was bone pain, reported in 10 patients (58.8 %), followed by anemic syndrome in 4 patients (23.5 %). Clinical examination revealed pallor and marked asthenia in 7 patients. Anemia was isolated in 70.5 % of patients and was predominantly normocytic (88.2 %). Thrombocytopenia and pancytopenia were noted in 3 patients (17.7 %) and in 2 patients (11.8 %), respectively ( Table 1 ). AL was diagnosed in 11 patients (3.7 %). There was a female predominance (sex ratio: 0.22). The mean age was 36.7 years (3–69 years). Clinical examination revealed tumor mass in 4 patients, pallor in 3, and asthenia in 3 patients. Biologically, anemia was isolated in 2 patients and was normocytic in both cases. Anemia was associated with hyperleukocytosis and thrombocytopenia in 3 patients, thrombocytopenia in 4 patients, and pancytopenia in 2 patients. BMA was performed in all patients, confirming the diagnosis of AL ( Table 1 ).

The study was conducted in accordance with the Declaration of Helsinki. All participants were informed about the objectives of the study, and informed consent was obtained prior to inclusion. Data were collected and analyzed anonymously to ensure patient confidentiality.

This study highlights that microcytic anemia does not always indicate IDA, and that isolated anemia may be the only abnormality associated with neoplasia or malignant hematological disease. Effective management of this common reason for consultation requires a comprehensive evaluation, considering both benign and malignant causes. It is crucial that clinicians continue to train and refine their diagnostic skills to provide optimal care for patients.

We analyzed the clinical and biological characteristics as well as the etiological spectrum of 296 patients with anemia who consulted the hematology department during the year 2022. The mean age was 47 years, which is consistent with the data reported by Zinebi et al., where the mean age was 48.4 years [ 7 ]. However, in the studies by Ben Ahmed et al. and Trenado et al., the population was older, with a mean age of 57.7 and 64.5 years, respectively [ 8 , 9 ]. We noted a female predominance (sex ratio = 0.38) which is consistent with the literature [ 7 – 9 ]. Anemic syndrome, characterized mainly by asthenia, dizziness, and pallor, was the most frequent CD (68 %), consistent with the findings of Zinebi et al., who reported similar presentations in 69 % of cases [ 7 ]. This could be explained by the severity of anemia observed with 50 % of patients. The mean Hb level was 7.9 g/dL with severe anemia (<8 g /dl) in 49.7 % of cases, results comparable to those reported by Zinebi et al., with a mean Hb of 8 g/dL [ 7 ]. This may reflect the high prevalence of iron deficiency and megaloblastic anemia, which often remain undiagnosed and well tolerated for long periods. Other cytopenia associated with anemia may point to the underlying etiology depending on whether the mechanism is central or peripheral. In our series, anemia was isolated in 200 patients (67.6 %), which is probably explained by the predominance of IDA. Bicytopenia or pancytopenia was observed in 31.7 % of cases, compared with 10 % reported by Zineb et al. [ 7 ], likely reflecting our hematology-based setting associating IDA, vitamin deficiencies and malignant hematologic disorders. IDA was the most common etiology, accounting for 55.7 % of cases, in line with global data identifying it as the most prevalent form of anemia worldwide, affecting over 1.2 billion individuals and occurring in both developing and developed countries [ 10 , 11 ]. Epidemiological studies on IDA show that women of childbearing age are more at risk, due to significant menstrual losses and increased iron requirements during pregnancy and breastfeeding [ 3 ]. Our results are consistent with literature, which highlights a female predominance in cases of IDA [ [12] , [13] , [14] , [15] , [16] ]. IDA is typically symptomatic, yet its gradual onset often allows good tolerance [ 17 ]. It can cause symptoms related to both the iron deficiency itself and the resulting anemia [ 18 ]. Signs of iron deficiency were present in only 9.6 % of cases, lower than reported in various studies, exceeding 20 %, with asthenia as the most frequent symptom, as in Nahon et al. [ 19 , 20 ]. The mean Hb level varies between studies, ranging from 6.7 to 8.3 g/dL, values close to those observed in our study, where the mean level was 7.8 g/dL [ [12] , [13] , [14] , 21 ]. The mean MCV was 67.3 fl, comparable to those reported in literature, with ranges between 65.7 and 66.1 fl [ 13 , 14 ]. In IDA, additional hematologic abnormalities may occur, including thrombocytosis and, more rarely, thrombocytopenia. Thrombocytosis, reported in up to 28 % of cases and typically moderate and asymptomatic [ 22 ], was observed in 23 % of our patients, whereas deficiency-related thrombocytopenia was rare, occurring in only 4 cases. This can be explained by the direct role of iron in regulating thrombopoiesis and its major role in megakaryocyte fragmentation and platelet release [ [23] , [24] , [25] , [26] , [27] ]. A digestive cause was identified in 13.3 % of cases (22 patients), while a gynecological cause was found in 4.2 % of cases. These results are consistent with the study by Al Saddik et al., which reported a higher prevalence of digestive causes than gynecological causes [ 12 ]. Megaloblastic anemia results from vitamin B12 and/or folic acid deficiency. The prevalence of megaloblastic anemia is estimated to be between 2 % and 40 % of patients [ 28 ]. Megaloblastic anemia was observed in 39 patients, representing 13.2 % of our study population. The mean age of this group was 62.7 years, which is consistent with the literature, ranging from 50 to 67 years [ 29 , 30 ]. A female predominance was observed, with a sex-ratio of 0.7. These results are consistent with those reported in the literature [ 7 , 30 ]. In our study, anemic syndrome was present in all patients, with digestive manifestations in 38.4 % and neurological symptoms in 25.6 %, findings comparable to those reported by Haissoune et al. and Belgith et al., who similarly described high frequencies of anemic and digestive presentations [ 33 , 34 ]. According to the literature, general signs such as asthenia, weight loss, and deterioration in general health are found in 20 to 50 % of patients with megaloblastic anemia [ 7 ]. On clinical examination, the anemic syndrome typically presents with a gradual onset. However, more severe forms, such as severe hematological involvement, hemolysis, pancytopenia, or pseudo-thrombotic microangiopathy, can occur in approximately 10 % of cases [ 32 ]. Generally, anemia is macrocytic and non-regenerative [ 35 , 36 ]. The mean Hb level reported in the various studies ranged from 5 g/dL to 8.1 g/dL, which is consistent with the mean level observed in our study, noted at 7.5 g/dL [ 31 , 33 , 34 ]. the mean MCV was 107.9 fL. Macrocytosis was noted across studies with mean MCV between 98.9 and 115.8 fL [ 30 , 31 , 33 , 34 ], though normal MCV may occur with coexisting iron deficiency [ 37 ]. Pancytopenia is commonly observed in megaloblastic anemia, often reflecting a delay in consultation [ [38] , [39] , [40] ]. It was reported in 38.4 % of cases in our study which is in line with literature [ 41 , 42 ]. Biermer's disease was found in 13 patients (33.3 %) of megaloblastic anemia. Our results differ from those reported by Zinebi et al., where Biermer's anemia was estimated to account for 62 % of cases of vitamin B12 deficiency anemia [ 7 ]. Biermer's anemia mainly affects people over the age of 60, with a predominance in females [ 43 ]. In our series, Biermer's anemia was diagnosed predominantly in women and elderly cases accounting for 46 %. Vitamin B12 deficiency due to insufficient dietary intake was found in 3 patients (13 %), mainly elderly and edentulous. It was around 3 % in the study by Belghith et al. [ 34 ]. In adults, gastrectomy and terminal ileal resection are rare causes of vitamin B12 malabsorption (<5 %). Belghith et al. reported malabsorption-related vitamin B12 deficiency in 9 % of cases [ 34 ], compared with 13 % of megaloblastic anemia cases in our study. In our series, we identified six cases of folic acid deficiency, mainly related to malnutrition. Drug-induced deficiency is also a common mechanism. This mechanism was found in 6.2 % of patients in the Takahashi et al. series, secondary to hydroxyurea, methotrexate, and other antifolate drugs [ 44 ]. These drugs can interfere with the absorption, transport, and cellular utilization of folates or compete with reducing enzymes [ 35 ]. Anemia is a common symptom in malignant blood disorders at the time of diagnosis or during the disease [ 45 ]. The prevalence of blood disorders varies widely in the literature. For example, it was estimated at 27 % in the series by Breedveld et al., while that reported by Zinebi et al. was lower, at 6 % [ 7 , 46 ]. In our series, the prevalence of malignant hematological disorders was estimated at 23.6 % of cases. The main diagnoses were dominated by MDS (10.8 % of cases), MM (5.7 %), and AL (3.7 %).

During the preparation of this work the authors used “Chatgpt” to assist in language editing, structural organization of the manuscript, and synthesis of descriptive tables. The tool was used to rephrase selected sections, and to format summary tables based on data provided by the authors. After using this AI tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the published article.

Anemia is a major public health problem, impacting physical growth, cognitive development, reproduction, and physical work capacity, thereby reducing human performance and potentially leading to cardiovascular and neurological events [ 1 ]. Establishing appropriate thresholds for defining anemia is essential to ensure its correct identification and prevent its negative effects [ 2 ]. Anemia results from a variety of causes and complex pathophysiological mechanisms, making some diagnoses complex and difficult to establish. It is often a sign associated with various diseases, thus requiring multidisciplinary management. It is very often trivialized and the diagnostic process is often ignored, leading to insufficient treatment or a lack of management [ 1 ]. The underlying causes of anemia are sometimes poorly understood; it can result from chronic inflammation or renal failure. Malnutrition, which is particularly common in the elderly, can lead to vitamin B12, folate, or iron deficiencies, which in turn lead to anemia. Furthermore, anemia could be an early sign of an undiagnosed malignant blood disorder, including myelodysplastic syndromes (MDS), multiple myeloma (MM), and even acute leukemia (AL) [ 1 ]. A simple diagnostic algorithm could be applied to the frequently encountered causes of anemia. If the cause is rarer, it would then be necessary to refer the patient to a specialist so as not to miss a diagnostic and therapeutic emergency [ 3 , 4 ]. Our study aims to investigate the epidemiological and clinical-biological profile and establish the etiological profile of anemia in the Clinical Hematology Department of Monastir.

AL : Acute Leukemia BMA : Bone Marrow Aspiration BMB : Bone Marrow Biopsy CBC : Complete Blood Count CD : Circumstance of discovery EGD : Esophagogastroduodenoscopy Hb : Hemoglobin IDA : Iron Deficiency Anemia MCV : Mean Corpuscular Volume MDS : Myelodysplastic Syndrome MM : Multiple Myeloma PBS : Peripheral Blood Smear Financial Disclosure Statement The authors declare that no financial support was received for this study.

The authors declare no conflicts of interest related to this manuscript.