Breathless Shadows of Silent Anemia: Unveiling the Hidden Challenge of Combined Iron and Vitamin B12 Deficiency: A Case Report

*Corresponding author: Debanjan Saha. Copyright © 2025 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution Liscense 4.0. Breathless Shadows of Silent Anemia: Unveiling the Hidden Challenge of Combined Iron and Vitamin B12 Deficiency: A Case Report Debanjan Saha 1, *, Lakshita Yadav 1 and Subhash Baddula 2 1 Department of Medicine, Military Hospital, Drugmulla, India. 2 Department of Surgery, Military Hospital, Drugmulla, India. World Journal of Biology Pharmacy and Health Sciences, 2025, 23(03), 383-391 Publication history: Received on 15 August 2025; revised on 20 September 2025; accepted on 23 September 2025 Article DOI: https://doi.org/10.30574/wjbphs.2025.23.3.0855 Abstract This case report presents a 44-year-old male army personnel and animal trainer who developed gradually progressive exertional breathlessness over three months, without other cardiorespiratory complaints, prompting differential consideration of occupational and respiratory etiologies owing to his professional environment and exposure to animals. Clinical assessment revealed marked pallor, and the patient’s laboratory investigations established a diagnosis of combined iron and vitamin B12 deficiency anemia, attributable to his recent switch to a vegetarian diet for six months. Hematological evaluation showed a microcytic hypochromic blood picture with low mean corpuscular volume and significantly reduced serum iron and vitamin B12 levels. No evidence was found for infectious, cardiopulmonary, or systemic disease, and classical causes of anemia were excluded through comprehensive testing. Management involved intravenous and oral supplementation of both iron and vitamin B12, leading to rapid resolution of breathlessness and normalization of hemoglobin values and other hematological indices within one week. This case highlights the necessity of thorough dietary history and micronutrient evaluation in adults with unexplained dyspnea, particularly in cases with recent dietary change, as dual deficiencies may obscure classical laboratory features of anemia and delay diagnosis. Early recognition and simultaneous correction of both nutrient deficits are critical in ensuring prompt recovery, preventing complications, and reinforcing the need for systematic diagnostic strategies in similar clinical presentations. Keywords: Iron deficiency anemia; Vitamin B12 deficiency; Microcytic hypochromic anemia; Nutritional anemia; Vegetarian diet; Parenteral vitamin B12 1. Introduction Breathlessness is defined by the American Thoracic Society as ‘‘a subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity.’’[1] Breathlessness has a widespread impact on the patient and their family. It is associated with poor quality of life, poor survival, and increased emergency care and hospital admissions with increased hospital length of stay and in-hospital adverse events.[2] Recognition that breathlessness may be persistent and disabling despite optimal treatment of the causative medical condition has led to recent naming and defining of chronic breathlessness syndrome.[3] Symptoms of anemia described in literature are fatigue, reduced cognitive function, breathlessness, lack of energy, weakness, and dizziness [4]. These symptoms can be interpreted as indicative of symptomatic anemia and may thus play a role in diagnostic and therapeutic decisions [5]. World Journal of Biology Pharmacy and Health Sciences, 2025, 23(03), 383-391 384 Iron deficiency anemia remains a major global health issue, contributing to approximately 800,000 deaths annually worldwide.[6] While anemia is historically associated with women of reproductive age and children, recent trends indicate an increasing risk among males, influenced by factors such as ethnicity and age—with age being a more significant risk factor in men compared to women.[7] Absolute iron deficiency arises from increased physiological iron requirements, inadequate dietary intake, impaired absorption, or chronic blood loss.[8] In contrast, functional iron deficiency describes a condition where iron stores are sufficient, but incorporation into erythroid precursors is impaired, often observed in settings of infection, inflammation, or malignancy.[9] This mechanism underlies the iron deficiency seen in various chronic diseases. Laboratory diagnosis is essential for confirming iron deficiency anemia. Initially, clinical suspicion is raised by features suggestive of anemia, including a low mean corpuscular volume (≤80 μm³) and a reduced mean hemoglobin concentration (≤13.7 g/dL). The next step involves assessing serum ferritin levels, where values ≤30 ng/mL confirm iron deficiency anemia. If serum ferritin results are inconclusive, further investigations such as total iron-binding capacity, serum iron, and transferrin saturation are performed. In iron deficiency anemia, total iron-binding capacity is elevated, whereas serum iron and transferrin saturation levels are decreased.[10] The mainstay of treatment for iron deficiency anemia is to replenish iron stores. This can be done through the administration of oral or parenteral iron supplements. There are tablets with varying dosages available for consumption in oral form as opposed to parenteral iron which is an individualized infusion. This discrepancy in dosing between the two routes requires an in-depth review of how the dosages of iron supplements can be standardized. Vitamin B12 (B12) is classified as a water-soluble vitamin, and is distinctive among all vitamins due to its large size, complexity, and that it contains the metal ion cobalt. It is necessary for appropriate nervous system function and for the metabolism of carbohydrate, protein, and fat. Deficiencies in B12 can lead to inefficient erythropoiesis and megaloblastic anemia [11] Populations at the highest risk for B12 deficiency include the elderly and those that follow a vegetarian or vegan diet. Deficiency within the elderly population is often the result of age-related gastric atrophy. This causes a decrease in acid and intrinsic factor production leading to B12 malabsorption. It should be noted, however, that causes such as pernicious anemia and food-bound malabsorption account for less than half of poor B12 status among the elderly. A high rate of deficiency among vegetarians or vegans exists because B12 is only naturally present in animal products, so those who do not consume diets high in fortified products are at risk [12] Here, we present a case of a young male, who presented with breathlessness and was detected to have anemia due to combined deficiency of Iron and Vit B12. 2. Case Report A 44-year-old man, an army personnel, an animal trainer by profession, presented with breathlessness on exertion. Insidious in onset around 03 months back, gradually progressive. There was no associated cough/ chest pain/ palpitations/ orthopnoea/ Paroxysmal Nocturnal Dyspnoea. No hemoptysis or bleeding from any other orifice noted. The differential diagnoses to be considered at this point are tabulated in Table 1. Table 1 Differential Diagnoses based on presenting complaints Serial No Broad Classification Differentials 1 Respiratory Causes Interstitial lung disease (including hypersensitivity pneumonitis, especially relevant for animal exposure) Occupational/environmental lung disease (e.g., chronic exposure-related lung disease due to animal dander, hay, mold) Chronic obstructive pulmonary disease (less likely if non-smoker, but possible with prior exposures) Pulmonary hypertension Subclinical or early chronic infections (e.g., tuberculosis) Asthma (adult onset, occupational, or allergic) Restrictive lung disease from other causes (e.g., sarcoidosis) World Journal of Biology Pharmacy and Health Sciences, 2025, 23(03), 383-391 385 2 Cardiac Causes Early heart failure (diastolic dysfunction, may occur without classic symptoms) Ischemic heart disease (occasionally presents without chest pain) Cardiomyopathy or other structural heart disease Pulmonary embolism (chronic or subacute forms) 3 Hematologic/Other Medical Causes Anemia (though bleeding not mentioned, may still consider) Methemoglobinemia or other hemoglobinopathies (can cause exertional dyspnea) Early systemic illness (e.g., thyroid disorders) 4 Neuromuscular and Miscellaneous Deconditioning (less likely in army personnel, but possible) Neuromuscular weakness (myasthenia gravis, motor neuron disease) Dysfunctional breathing or anxiety-related dyspnea In this case, animal trainer occupation raises the suspicion for hypersensitivity pneumonitis and other occupational lung diseases as especially relevant differentials, in addition to common cardiopulmonary and hematological causes. Individual belonged to the state of Tamil Nadu, presently posted and working at Jammu and Kashmir for the last one year. He is not addicted to alcohol/ tobacco in any form/ any known abusive substance. He consumed mixed die, though for around 06months prior to presentation, he had switched to a vegetarian diet. There is no significant illness in the past. No hospital admissions for the patient in his life thus far. There is no similar illness among family members. 2.1. On Examination General condition – Good. Height – 174cm. Weight – 86kg. BMI – 28.4kg per square metre. Blood Pressure – 136/80mmHg, measured in right arm and 128/82mmHg, measured in left arm, both in supine posture, with no postural drop in blood pressure noted. Pallor present. No cyanosis/ clubbing/ edema/ icterus noted. Jugular venous pressure was not elevated. There was no cervical/ axillary or inguinal lymphadenopathy in the patient. Systemic Examination: Vesicular breath sounds appreciated in both lung fields, with no adventitious sounds. Abdominal examination did not reveal any hepatosplenomegaly. Examination of the cardiovascular and Neurological system was unremarkable. The differentials that would now be considered are tabulated in Table 2. Table 2 Differentials to be considered after clinical examination Serial No Grade of possibility Details 1 Most likely Anemia-Related Causes (Especially Nutritional) Pallor is a key finding, supporting anemia as a probable cause of exertional dyspnea. The switch to a vegetarian diet in the last 6 months increases the risk for iron deficiency or potentially vitamin B12 deficiency anemia. Nutritional anemia is highly likely, especially in this age group and context. Chronic Disease related Anemia (Secondary Anemia) While possible, there is no overt evidence of chronic infection, inflammation, or malignancy (no lymphadenopathy, hepatosplenomegaly, systemic symptoms). 2 Still Possible, But Less Likely Hypersensitivity Pneumonitis or Interstitial Lung Disease Absence of adventitious sounds (crackles, wheeze), normal respiratory examination, and no signs of clubbing make significant interstitial or parenchymal lung disease less likely at present. Other Occupational Lung Disease World Journal of Biology Pharmacy and Health Sciences, 2025, 23(03), 383-391 386 Less likely with a normal respiratory exam and no chronic findings. 3 Unlikely Differentials Cardiac Disease Lack of heart failure signs, normal cardiovascular exam, and no prior symptoms make primary cardiac etiology unlikely. Chronic Infections, Neoplasia, Systemic Diseases No suggestive physical signs: no lymphadenopathy, organomegaly, or systemic symptoms. 2.2. Investigations On arrival: (Initial Blood Picture) Hb – 10.3g/dl; Total Leucocyte count – 8000 per microL; Platelet count – 2.65 lakhs per microL; Neutrophils – 67%; Lymphocytes – 21%; Monocytes – 08%; Eosinophils – 04%. Mean Corpuscular Volume – 63.8fL; Mean Corpuscular Hemoglobin – 18.5pg; Mean Corpuscular Hemoglobin Concentration – 29.0g/dL; Packed Cell Volume – 35.7%. Peripheral Blood Smear: RBC MORPHOLOGY: Predominantly Normocytic Normochromic to microcytic hypochromic RBCs with anisocytosis. (Figure 1) • WBC MORPHOLOGY: 7500/uL Neutrophils 66% Lymphocytes 24% Monocytes 03% Eosinophils 07% • PLATELETS: Adequate on smear • IMPRESSION: Microcytic hypochromic blood picture with relative eosinophilia • Liver Function test, Renal Function Test, Thyroid profile – Normal • ECG – Normal Sinus Rhythm • Chest X Ray PA view – Within Normal Limits Figure 1 Peripheral blood smear stained with Wright's stain under 1000x oil immersion microscope showing hypochromic microcytic red blood cells most likely due to iron deficiency anemia. World Journal of Biology Pharmacy and Health Sciences, 2025, 23(03), 383-391 387 In view of microcytic hypochromic picture, patient was made to undergo Blood examination for Iron Studies and HPLC (Table 3). In view of his vegetarian diet over last 03 months, he underwent evaluation of Blood levels of Vit B12. Relevant investigations are chronologically arranged in Table 4. Table 3 Blood for HPLC: Tabulated report Ser No Disorder Parameter Biological ref interval Result Unit Remarks 1 Sickle Cell Anaemia (Hb SS) S-Band N.D N.D % Negative F-Band <=2 0.50 % A-Band 60 - 98 97.10 % A2-Band 1.3 - 3.5 2.40 % 2 Beta thalassemia A2-Band 1.3 - 3.5 2.40 % Negative A-Band 60 - 98 97.10 % F-Band <=2 0.50 % 3 Sickle Cell Disease S-Band N.D N.D % Negative F-Band <=2 0.50 % D-Band N.D N.D % A-Band 60 - 98 97.10 % A2-Band 1.3 - 3.5 2.40 % 4 Variant hemoglobinopathies (C, D, H, bart band) including Hb E (Var Hb) F-Band <=2 0.50 % Negative C-Band N.D N.D % E-Band N.D N.D % A-Band 60 - 98 97.10 % D-Band N.D N.D % Unknown N.D N.D % Blood for Iron Studies: Serum iron – 34.21 µg/dL (65-175); TIBC – 428.25 µg/dL (250-450); Transferrin Saturation – 7.99% (20-50); Serum Ferritin – 28.3 ng/ml (Male: 30-400); Vit B12 (Cyanocobalamin) <50.00 pg/ml (180-914) 3. Treatment Post admission, patient’s blood samples were sent for Vit B12 levels, HPLC and Iron studies. Reports of Vit B 12 levels were received at the earliest which showed a deficiency. Supplementation in the form of inj and oral Vit B12. Two days later, on arrival of reports of HPLC and Iron studies, patient was confirmed to have iron deficiency as well. Deficiency of iron was calculated according to Ganzoni’s equation and injectable iron in the form of Inj Ferric Carboxymaltose was administered. Table 5 gives the timeline of events for the patient. Table 4 Relevant investigations chronologically arranged Day 03 days Prior to admission On Day of Admission 02 days later 04 days later 08 days later Events Nil Inj Vit B12 started – 1000microg iv daily Inj FCM given (Blood sampling done just prior) 07 doses of daily Vit B12 inj completed Hb (g/dl) 9.7 10.3 10.9 11.1 12.8 World Journal of Biology Pharmacy and Health Sciences, 2025, 23(03), 383-391 388 TLC (per microL) 9100 8000 9300 7200 8700 Platelet (lakhs per microL) 2.51 2.65 2.31 2.10 2.22 MCV (fL) 58 63.8 64.6 64.6 66.2 MCH (pg) 19 18.5 18.7 19.3 20.4 MCHC (gm/dl)S 33 29 29 29.9 30.8 Table 5 Timeline of events Occurrence of event Action Taken 03 days prior to admission Patient detected to have anemia elsewhere Patient referred to our hospital On Day of admission Anemia confirmed in patient PBS shows microcytic hypochromic anemia Samples for Vit B12, Iron studies and HPLC sent On Day 1 of admission Vit B12 deficiency confirmed Inj Vit B12 1000µg iv q24h x 07 days started On Day 2 of admission Deficiency of Iron confirmed No hemoglobinopathies detected Inj FCM 1000mg iv on Day 2 On Day 3 of admission Inj FCM 500mg iv on Day 3 On Day 8 of admission Patient asymptomatic Discharged from hospital Ganzoni equation: Iron Deficiency = [2.4 x (Target Hb – Actual Hb) x Body Weight + Iron Stores] mg = [2.4 x (15 – 10.3) x 86 + 500] mg = 1470.08mg 4. Follow up and Outcomes Patient responded well to treatment. Symptomatic improvement was noted. Breathlessness resolved gradually overs 01 week. Lab parameters improved in the form of increase in Hemoglobin levels (Figure 2), Serum Ferritin levels (>1000ng/ml) and MCV. Patient was given inj Iron preparation x 02 days, followed by Oral Iron supplementation. Inj Vit B12 was supplemented on daily basis for 01 week followed by weekly doses for 04 weeks followed by plan for monthly injections. World Journal of Biology Pharmacy and Health Sciences, 2025, 23(03), 383-391 389 Figure 2 Graphical representation of improvement in Hemoglobin levels after starting injectable vitamin B12 and intravenous iron treatment 5. Discussion This case highlights the importance of considering nutritional deficiencies as a cause of exertional dyspnea in otherwise healthy individuals, particularly when dietary habits have recently changed. Although the initial suspicion favored cardiopulmonary or occupational lung diseases due to the patient’s profession and environment, the clinical finding of pallor and subsequent investigations established a dual deficiency of Vitamin B12 and iron as the underlying etiology. The coexistence of these deficiencies explained the mixed red cell morphology and symptom severity, while timely correction with parenteral supplementation resulted in rapid clinical and hematological improvement. This case underlines the need for a comprehensive yet stepwise diagnostic approach, where broad differentials are methodically narrowed, ensuring prompt identification and management of reversible causes of anemia. Anemia is a condition characterized by a reduction in the number of red blood cells (RBCs) or the concentration of hemoglobin within them, leading to decreased oxygen-carrying capacity of the blood. It may manifest clinically with symptoms such as fatigue, palpitations, headache, and shortness of breath. Physical signs like conjunctival and palmar pallor, although having limited sensitivity and moderate specificity for diagnosing anemia, remain useful particularly when laboratory resources are unavailable. In both clinical practice and public health settings, hemoglobin concentration measurement is the most widely used and reliable indicator for diagnosing anemia. Anemia can be categorized based on its underlying etiology, such as increased red blood cell loss or decreased production. It may present as microcytic anemia—commonly caused by iron deficiency or thalassemia; normocytic anemia—which is often associated with inflammatory conditions; or macrocytic anemia—typically resulting from vitamin B12 or folate deficiencies, liver disease, myelodysplasia, or hypothyroidism.[13] The World Health Organization (WHO) identifies several determinants of anemia, including biological factors (such as nutrient deficiencies and malnutrition, growth, physiological state, sex, age, and race); infections and inflammation (including soil-transmitted helminth infections, schistosomiasis, malaria, HIV, tuberculosis, and low-grade inflammation); genetic hemoglobin disorders; blood loss and contraceptive use; as well as social, behavioral, and environmental factors.[13] Iron deficiency is the most prevalent micronutrient deficiency associated with anemia. Absolute iron deficiency occurs when body iron stores are insufficient to meet physiological needs, whereas functional iron deficiency arises when iron stores are adequate but cannot be utilized due to impaired mobilization and absorption, often to limit iron availability to pathogens. Both forms may coexist within individuals or populations. Rare micronutrient deficiencies implicated in anemia include vitamins A, B2, B6, B9, B12, C, D, and E, as well as copper and zinc. These deficiencies may develop when intake fails to meet the body's demands over time, owing to factors such as World Journal of Biology Pharmacy and Health Sciences, 2025, 23(03), 383-391 390 low consumption, poor bioavailability, presence of absorption inhibitors, increased physiological needs during periods like infancy, adolescence, or pregnancy, or enhanced losses. Hemoglobin (Hb) measurement in blood is the most common method to diagnose anemia. However, hematocrit (packed cell volume) is also used. For more detailed (causal) insights, red blood cell parameters—such as mean cell volume (MCV), mean cell hemoglobin concentration (MCHC), and reticulocyte count—can be informative. Additional tests include examination of a peripheral blood smear, hemoglobin electrophoresis (or high-performance liquid chromatography), measuring micronutrient biomarkers, using Hb color scales, or observing clinical signs. Depending on which indicator is used, different individuals may be identified as anemic, since each test reflects different underlying metabolites or physiological processes. Combined iron and vitamin B12 deficiency is an important but often under-recognized cause of anemia, as the two deficiencies may mask or modify each other’s hematological features. While iron deficiency typically produces a microcytic, hypochromic anemia and vitamin B12 deficiency result in a macrocytic, megaloblastic picture, their coexistence can yield a mixed or normocytic morphology, making diagnosis challenging on peripheral smear alone. Macrocytosis, the hallmark of cobalamin/folate deficiency anemia, is frequently absent. Clinicians have to be aware of coexisting conditions that can mask the macrocytosis expression of megaloblastic anemia, especially iron deficiency. The clinical presentation often includes nonspecific symptoms such as exertional breathlessness, fatigue, and pallor, but neurological manifestations of B12 deficiency may be attenuated or overlooked in the presence of iron deficiency. Dietary factors, particularly vegetarianism, chronic blood loss, and malabsorption syndromes, are major contributors. Recognition of this dual deficiency requires comprehensive evaluation with complete blood counts, iron studies, and vitamin B12 levels, as treating only one component may lead to suboptimal recovery or persistent symptoms. Early identification and combined supplementation are crucial for rapid hematological correction and prevention of longterm complications Individuals with chronic anemia frequently exhibit few or no symptoms, and the condition is often detected incidentally during routine laboratory assessments. Although anemia has been linked to reduced quality of life and various adverse health outcomes, these associations are not necessarily causal and may be influenced by confounding factors. In primary and outpatient care settings, clinicians commonly rely on patient history and reported symptoms to guide their diagnostic evaluation. Appropriate treatment results in dramatic clinical and laboratory responses in most patients. 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