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Masked Iron Deficiency in Macrocytic presentation of Dimorphic Anemia with Diabetes: a case report

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  • Dr Varsha's Health Solutions

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Anemia is a health condition contributing significantly to morbidity and decreased productivity worldwide. Though iron deficiency in women is the leading cause, anemia in men is also an important health burden and is often underdiagnosed. Sometimes anemia can present in a dimorphic form with both macrocytic and hypochromic microcytic components due to multiple nutrient deficiencies or co-existing health conditions. It is important to therefore keep this in mind during clinical diagnosis and laboratory evaluation. Anemia is more common in diabetes and can also be associated with higher cardiovascular and renal risk. Treatment with both appropriate nutritional supplements and diet-lifestyle modification would be the right approach to manage anemia in such patients.
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International Journal of Medical Science and Innovative Research (IJMSIR)
IJMSIR : A Medical Publication Hub
Available Online at: www.ijmsir.com
Volume 5, Issue –3, May - 2020, Page No. : 332 - 336
Corresponding Author: Dr Varsha Narayanan, ijmsir, Volume – 5 Issue - 3, Page No. 332 - 336
Page 332
ISSN- O: 2458 - 868X, ISSNP: 2458 – 8687
Index Copernicus Value: 68 . 16
PubMed - National Library of Medicine - ID: 101731606
Masked Iron Deficiency in Macrocytic presentation of Dimorphic Anemia with Diabetes: a case report.
Dr Varsha Narayanan, Consultant Family Medicine and Holistic Health: Dr Varsha’s Health Solutions, Andheri west,
Mumbai.
Corresponding Author: Dr Varsha Narayanan, Consultant Family Medicine and Holistic Health: Dr Varsha’s Health
Solutions, Andheri west, Mumbai.
Citation this Article: Dr Varsha Narayanan , “Masked Iron Deficiency in Macrocytic presentation of Dimorphic Anemia
with Diabetes: a case report”, IJMSIR- May - 2020, Vol 5, Issue -3, P. No. 332 – 336.
Type of Publication: Case Report
Conflicts of Interest: Nil
Abstract
Anemia is a health condition contributing significantly
to morbidity and decreased productivity worldwide.
Though iron deficiency in women is the leading cause,
anemia in men is also an important health burden and is
often underdiagnosed. Sometimes anemia can present
in a dimorphic form with both macrocytic and
hypochromic microcytic components due to multiple
nutrient deficiencies or co-existing health conditions. It
is important to therefore keep this in mind during
clinical diagnosis and laboratory evaluation. Anemia is
more common in diabetes and can also be associated
with higher cardiovascular and renal risk. Treatment
with both appropriate nutritional supplements and diet-
lifestyle modification would be the right approach to
manage anemia in such patients.
Keywords: Anemia, Lifestyle, Macrocytic, Nutrition
Introduction
Anemia affects 1.62 billion people globally, almost
1/4th of the population at some time or the other.1 In
India, the overall prevalence is almost 40%, being
much higher in children and women. Therefore, anemia
screening focuses on women and children, where it is
seen more due to malnutrition and infections, while
anemia in men may often be underdiagnosed. The
global incidence of anemia in men is around 12.7%.1 In
men, a Hemoglobin below 13g/dL. (Mild 11-12.9g/dL;
moderate 8-10.9g/dL and Severe <8g/dL)2 Anemia
among men in India is an important public health
problem, with the prevalence being around 23·2% with
an estimated 21·7% of anemic men having moderate or
severe anemia.3 Iron deficiency is the commonest cause
of anemia in India but around 17.5% of anemia cases
are of Dimorphic anemia which presents with either a
microcytic hypochromic (initially normocytic
normochromic), or a macrocytic clinical predominance
in 37% and 63% respectively. Therefore, it is important
to rule out masked iron deficiency and dimorphic
anemia in patients who present a characteristic
macrocytic blood picture on laboratory diagnosis as is
also seen in the case study presented.5
Patient History
A 49-year-old male patient who was a corporate
manager reported with symptoms of fatigue and
weakness. On taking a detailed history, the patient
elaborated that he feels tired frequently, is low on
energy levels and feels week as compared to his usual
working capacity and ability. He also revealed that he
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experiences palpitation, and a feeling of slight
breathlessness and early tiring on exercising. He often
has headaches which are more towards the latter part of
the day. He also expressed that he feels anxious and
difficulty in sleeping on 2-3 nights every week. No
history of cough, chest pain, breathlessness at rest,
weight loss, dizziness or any other
localized/generalized pain. Patient said he often
experienced gas and constipation for which he would
take herbal supplements.
The patient was diagnosed as hypertensive 6 months
ago, and prescribed Olmesartan 20mg once daily. He is
also a known Diabetic (diagnosed 5 years ago),
controlled on Metformin-Vildagliptin combination
500mg/50mg once daily. He monitors his blood sugar
weekly with SMBG (Self-Monitoring of Blood
Glucose) by Glucometer. The patient has also been
prescribed Rosuvastatin-Fenofibrate 10mg/160mg
combination for lipid control since last 5 years. He has
no history of any cardiac disease. He smokes 1-2
cigarettes/day for past 25 years, and takes alcohol
occasionally socially. He is married with 2 children;
and a vegetarian. On week days his diet was more
packaged/processed food dominant and relatively low
on vegetables, due to high travelling. In his family
history, his father has hypertension and diabetes
present, controlled on medication.
The patient had gone to a general physician a month
back with the same complaints of weakness, fatigue,
low energy, and reduced exercise tolerance and work
capacity. He was evaluated with a Complete Blood
Count (CBC) which showed a decreased Hemoglobin
(Hb), Red Blood Cell (RBC) Count, and Hematocrit,
with an increased Mean Corpuscular Volume (MCV)
and Mean Corpuscular Hemoglobin (MCHC),
suggesting a diagnosis of Macrocytic Anemia. The Red
cell Distribution Width (RDW) also showed an
increase. (Table 1 at baseline). The Total and
Differential White Blood Cell (WBC) count and the
Platelet count were normal.
The patient was prescribed Folic acid (1.5 mg/d) orally
and given intramuscular Vitamin B12 injections
1500ug (as a combination injection with 100mg
B6+100mg B3) on alternate days for 2 weeks. (total 7
injections).
The patient had also gone for an Eye test, which
revealed 6/6 distance vision in both eyes, and no
change in number of his +1.5 reading glasses for both
eyes. Eye examination including fundus was normal.
Further Patient Evaluation
Patient’s pulse rate initially was 88 beats/minute in the
beginning and 80 beats/minute at the end of
examination. Blood Pressure was 128/80 mm Hg and
Respiratory Rate 12 breaths/minute. He was well
oriented. Weight was 79kg. General examination
showed pallor of the lower conjunctiva, while no
icterus or pedal edema was seen. Heart sounds and lung
auscultation were normal. Routine abdominal
examination also appeared normal.
The patient was advised to repeat CBC, along with Iron
Studies and Vitamin B12 levels. He was also advised to
check blood sugar (fasting and post prandial), HbA1C,
Vitamin D levels, Renal function test and lipid profile
along with ECG and stool and urine test.
CBC revealed no change in Hemoglobin as compared
to baseline after 1 month of taking Oral folate
supplementation and 2 weeks of alternate day B12
injections. MCV had come down towards upper limit of
normal and MCH had normalized, as compared to
significantly high values of both these parameters one
month back. (Table 1- at 1 month)
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Iron studies revealed significantly decreased total blood
iron as well as transferrin saturation, with the total Iron
binding capacity in the upper range of normal (Table
2). Vitamin B12 (>2000pg) was much above the
normal range.
Blood sugar, HbA1C, and Lipid profile was well
controlled, Vitamin D was in normal range, Renal
function tests as well as Urine examination was normal
(no albuminuria or glycosuria). ECG showed a
borderline Left Axis Deviation (LAD) and sinus
rhythm. Stool test was normal with no presence of
parasites, or occult blood.
Based on this, a diagnosis of Dimorphic anemia
(masked Iron deficiency anemia) of moderate severity,
was made.
The patient was started on Heme Iron Polypeptide
12mg, 2 tablets daily in the morning after breakfast
with Vitamin C 500mg after breakfast and dinner. The
patient was also given a multivitamin supplement
which had Omega 3 Fatty acids 150 mg, Folic acid 5
mg, Vitamin B12 (as Methyl cobalamin) 500 mcg,
Mixed carotene 10.33 mg, Copper 1 mg, Manganese 2
mg, Selenium 40 mcg, Chromium 65 mcg, and Zinc
22.5 mg. Appropriate dietary recommendation on
nutritious food (with more vegetables, fruits, whole
grains and proteins), increased water intake, and
lifestyle modification (right exercise, smoking
restriction, along with relaxation techniques for anxiety
and better sleep) were also given.
Follow up
CBC was repeated after 1 month. Hemoglobin had
improved significantly, with RBC count and MCV
entering normal range. MCH and MCHC had reduced
unmasking the Iron deficiency anemia. Hematocrit had
also almost normalized. RDW was still high but
decreased significantly over 1 month (Table 1 at 2
months). Patient said that he felt more energy and less
tiredness than before.
Patient was continued on the same treatment for a
further 2 months after which his CBC and other blood
tests were repeated. His Hb had further improved
significantly and entered normal range with
normalization of MCH and MCHC and reduction in
RDW. (Table 1 at 4 months). BP, Blood Sugar and
HbA1C were normal. Patient said his symptoms had
significantly improved and he felt his working capacity
was optimum. He no longer experienced palpitation or
breathlessness on exercising half hour daily, and also
did not suffer from frequent headaches as before. He
did not complain of any adverse effects after starting
Heme Iron and other supplements. Patient was asked to
continue same supplements for an additional 3 months,
and incorporate dietary and lifestyle advise on a long-
term basis.
Discussion
Dimorphic anemia can be caused by the simultaneous
deficiency of iron, B12 and folate which can be seen
due to diets low on green vegetables and animal
products, as was seen in this case. Other causes include
bone marrow suppression (will show pancytopenia on
CBC) or parasitic infection and occult blood loss (will
be seen in stool test), and malabsorption or
inflammatory diseases of the bowel.6,7 Since
macrocytosis is the more common presentation of
dimorphic anemia, seen by both peripheral blood and
bone marrow examination, it is important to perform
Iron studies to rule out masked iron deficiency.4
Initially in this patient, decreased Hemoglobin, along
with increased MCV, MCH, and RDW was suggestive
of macrocytic anemia, while the underlying Iron
deficiency was gradually revealed as B12 and folate
were supplemented, and Iron studies performed. Such
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patients often do not respond symptomatically or with
satisfactory increments in Hemoglobin to folic acid and
B12 supplements alone. While folate is usually
supplemented orally, B12 injections are recommended
in severe deficiency and malabsorption syndromes,
while oral B12 replacement may be considered for
patients in mild-moderate cases with no absorption or
compliance concerns.8
Patients with type 2 diabetes mellitus are twice more
likely to be prone to anemia than the patients without
diabetes.9 Anemia is often unrecognized in 25% of
diabetic patients and is also an independent risk factor
in diabetic patients for heart disease and renal failure.
LAD especially in hypertensive relatively younger
ambulatory adults without cardiac symptoms or disease
can indicate association with glucose intolerance.10
Therefore, screening for and treating Anemia is of
multidimensional importance in Diabetic patients, and
such patients should also be well monitored for Blood
Sugar and Blood pressure control and presence or onset
of cardiac/renal disease.
Intravenous Iron is recommended for patients with
severe anemia, or those with inflammation (due to
kidney disease, heart failure, or rheumatological
diseases), patients who cannot tolerate oral iron, or are
noncompliant with oral iron therapy. 11 Gastro-
intestinal side effects like nausea, indigestion and
constipation along with low and unpredictable
absorption of iron salts limits the implementation and
benefits of oral iron therapy. This patient had moderate
anemia, no inflammatory disease and showed
willingness to comply to oral therapy. Heme iron
polypeptide was chosen as the suitable iron preparation
due to its higher iron content, bioavailability, real world
efficacy-consistency and tolerance.12
Iron absorption, utilization and RBC incorporation with
Heme Iron has seen to be significantly higher than
Ferrous Fumarate, and Ferrous Sulphate even with
meals, and relatively unaffected by body Hepcidin
levels.13,14 A study comparing oral HIP and intravenous
iron saccharate complex in iron deficiency anemia,
showed no significant differences between groups for
change in Hb (average 3g/dL change) and ferritin levels
at 3 months.15 The patient in this case responded well to
treatment with Heme Iron with both satisfactory Hb
incrementation and tolerance. Vitamin C in this case
was given to enhance non-heme iron absorption from
diet as vegetarian food does not contain heme iron and
has very low levels of B1216. Folate and B12
supplements were also continued along with other B
complex vitamins and minerals orally.
Conclusion
Anemia can present in a dimorphic form, with a
predominant picture of macrocytosis, masking the
underlying Iron deficiency. This needs to be considered
and evaluated both clinically and by laboratory tests,
and treatment given accordingly. Diet and Lifestyle
assessment and modification form an important part of
therapy along with appropriate dose and formulations
of nutritional supplements. Iron formulations like Heme
Iron can be suitable options to improve absorption,
utilization and tolerance to oral iron. Anemia is more
common in patients with Diabetes, and can increase
cardiovascular and renal risk in such patients who
should therefore be evaluated, monitored and treated
for the same timely.
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Table 1: RBC profile and parameters in CBC
Baseline
1 month
(1 month of B12-
Folate)
2 months
(1 month of Iron
- HIP)
- HIP)
Lab Reference
Range
Unit
Hemoglobin
9.6
9.5
10.9
13-18
g/dL
RBC Count
2.38
2.92
4.49
4.7-6.0
Million/ μL
Hematocrit
29.5
32.4
41.1
42-52
%
MCV
123.9
111
91.5
78-100
fL
MCH
40.3
32.5
24.3
27-31
pg
MCHC
32.5
29.3
26.5
32-36
g/dL
RDW-CV
17.9
26.9
21.8
11.5-14.0
%
CBC: Complete Blood Count; RBC: Red Blood Cell,
MCV: Mean Corpuscular Volume, MCH: Mean
Corpuscular Hemoglobin, MCHC: Mean Corpuscular
Hemoglobin Concentration, RDW-CV: Red cell
Distribution Width (Coefficient Variation), HIP: Heme
Iron Polypeptide.
Table 2: Iron and B12 studies after 1 month of Folate-B12 treatment
Value
Lab Reference range
Unit
Iron
26.4
Male: 65-175
mcg/mL
Total Iron Binding Capacity
496
Male: 225-535
mcg/mL
Transferrin Saturation
5.32
13-45
%
Vitamin B12
>2000
211-911
pg/ml
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Background: Population-based studies on anaemia in India have mostly focused on women and children, with men with anaemia receiving much less attention despite anaemia's adverse effect on health, wellbeing, and economic productivity. This study aimed to determine the national prevalence of anaemia among men in India; how the prevalence of anaemia in men varies across India among states and districts and by sociodemographic characteristics; and whether the geographical and sociodemographic variation in the prevalence of anaemia among men is similar to that among women to inform whether anaemia reduction efforts for men should be coupled with existing efforts for women. Methods: In this cross-sectional study, we analysed data from a nationally representative household survey carried out from January, 2015, to December, 2016, among men aged 15-54 years and women aged 15-49 years in all 29 states and seven Union Territories of India. Haemoglobin concentration was measured using the portable HemoCue Hb 201+ (HemoCue AB, Ängelholm, Sweden) and a capillary blood sample. In addition to disaggregating anaemia prevalence (separately in men and women) by state and age group, we used mixed-effects Poisson regression to determine individual-level and district-level predictors of anaemia. Findings: 106 298 men and 633 305 women were included in our analysis. In men, the prevalence of any anaemia was 23·2% (95% CI 22·7-23·7), moderate or severe anaemia was 5·1% (4·9-5·4), and severe anaemia was 0·5% (0·5-0·6). An estimated 21·7% (20·9-22·5) of men with any degree of anaemia had moderate or severe anaemia compared with 53·2% (52·9-53·5) of women with any anaemia. Men aged 20-34 years had the lowest probability of having anaemia whereas anaemia prevalence among women was similar across age groups. State-level prevalence of any anaemia in men varied from 9·2% (7·7-10·9) in Manipur to 32·9% (31·0-34·7) in Bihar. The individual-level predictors of less household wealth, lower education, living in a rural area, smoking, consuming smokeless tobacco, and being underweight and the district-level predictors of living in a district with a lower rate of primary school completion, level of urbanisation, and household wealth were all associated with a higher probability of anaemia in men. Although some important exceptions were noted, district-level and state-level prevalence of anaemia among men correlated strongly with that among women. Interpretation: Anaemia among men in India is an important public health problem. Because of the similarities in the patterns of geographical and sociodemographic variation of anaemia between men and women, future efforts to reduce anaemia among men could target similar population groups as those targeted in existing efforts to reduce anaemia among women. Funding: Alexander von Humboldt Foundation.
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Background: Iron deficiency anemia is a common condition affecting the quality of life, as well as maternal and fetal outcomes in non-pregnant and pregnant women respectively. Oral iron supplementation represents the most convenient and cost-effective form of therapy. Conventional non-heme iron oral supplements are known to be associated with poor gastrointestinal tolerability, and therefore reduced compliance and efficacy. Oral Heme iron supplementation represents a better tolerated and more bioavailable option for oral iron therapy. Though evidence of its efficacy and tolerability are available through some randomized clinical trials, real world data from its regular use in pregnant and non-pregnant patients is lacking. Methodology: 378 non-pregnant and pregnant women visiting 56 gynecology clinics across India with an in-clinic diagnosis of iron deficiency anemia based on baseline laboratory evaluation of hemoglobin (Hb), along with ferritin, MCV and hematocrit, were treated with daily tablets of heme iron polypeptide (HIP) for an average duration of 3 months. Laboratory parameters assessed at baseline were repeated at final follow up and the patients' tolerability to therapy was also recorded. Results: In non-pregnant women, the average rise in Hb was 1.17, 2.06 and 3.28 (g/dl), in groups with baseline mild, moderate, and severe anemia, while in pregnant women, the average Hb rise was 2.70 and 3.53 (g/dl) in groups with baseline moderate and severe anemia. The rise in Hb was highly significant in both pregnant and non-pregnant women with baseline moderate and severe anemia. There was also a significant decline in the number of patients with moderate and severe anemia, as well as in percentage patients with low ferritin, MCV and hematocrit values. The tolerability of HIP was satisfactory with a treatment adverse event related discontinuation rate of less than 0.8%. Conclusion: This study suggests that oral HIP therapy can be an effective treatment option in pregnant and non-pregnant women with iron deficiency due to its better gastrointestinal tolerability and efficacy in improving hematological parameters.
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Objectives: Anemia is one of the world’s leading causes of considerable perinatal morbidity and mortality. This study designed to compare the efficacy and safety of Heme iron polypeptide (Proferrin®-ES) versus iron saccharate complex (Ferrosac) in treatment of iron deficiency anemia during pregnancy. Methods: Two hundred and sixty (260) pregnant women with hemoglobin level below 10 gm/dl due to iron deficiency anemia were included in this study and randomized to receive either; intravenous Iron Saccharate (IV group) or oral Proferrin®-ES (PO group) for correction of iron deficiency anemia during pregnancy. Treatment efficacy checked by comparing pre-treatment values of hemoglobin, serum ferritin, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and reticulocytes count by the 3-months` post-treatment values. Results: The 3- months` post-treatment hemoglobin level increased compared to the pre-treatment level without any significant difference between the two studied groups (from 8.5 ± 3.5 to 11.3 ± 1.3 gm/dl in PO group and from 8.7 ± 2.5 to 11.7 ± 0.9 gm/dl in IV group). In addition; the 3-months` post-treatment ferritin level, increased compared to the pre-treatment level without any significant difference between the two studied groups (from 19.4 ± 4.9 to 118.8 ± 7.1 ug/l in PO group and from 15.3 ± 5.6 to 122.3 ± 6.4 ug/l in IV group). 1.6% (2/124) of the studied women developed gastrointestinal intolerance and upset with oral Proferrin®-ES (insignificant difference and excluded from the study) and no other side effects recorded with oral Proferrin®-ES. Conclusion: HIP (Proferrin®-ES) is an effective, safe, well tolerable oral iron preparation as well as intravenous iron saccharate complex for treatment of iron deficiency during pregnancy; it increases the hemoglobin and replaces the depleted iron store.
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Objective. To provide clinicians with evidence-based guidance for iron therapy dosing in patients with iron deficiency anemia (IDA), we conducted a study examining the benefits of a higher cumulative dose of intravenous (IV) iron than what is typically administered. Methods. We first individually analyzed 5 clinical studies, averaging the total iron deficit across all patients utilizing a modified Ganzoni formula; we then similarly analyzed 2 larger clinical studies. For the second of the larger studies (Study 7), we also compared the efficacy and retreatment requirements of a cumulative dose of 1500 mg ferric carboxymaltose (FCM) to 1000 mg iron sucrose (IS). Results. The average iron deficit was calculated to be 1531 mg for patients in Studies 1-5 and 1392 mg for patients in Studies 6-7. The percentage of patients who were retreated with IV iron between Days 56 and 90 was significantly (p < 0.001) lower (5.6%) in the 1500 mg group, compared to the 1000 mg group (11.1%). Conclusions. Our data suggests that a total cumulative dose of 1000 mg of IV iron may be insufficient for iron repletion in a majority of patients with IDA and a dose of 1500 mg is closer to the actual iron deficit in these patients.
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Introduction: We are increasingly noticing isolated left axis deviation (LAD) in electrocardiogram in younger people with diabetes without obvious heart disease and association of LAD with glucose intolerance has not been explicitly raised before. We planned a study of ambulatory adults with borderline (0° to -30°) and moderate-to-marked (<-30° to -90°) LAD looking into their possible association with glucose intolerance with fasting plasma glucose (FPG)≥100 mg/dL. Methods: We consecutively enrolled adults aged 30 or more, with electrocardiogram normal duration QRS axis between 0° to -90°, without cardiac symptoms, not on any medication, attending outdoor-clinics for health checkup. Results: Out of 100 participants enrolled, about 90% were aged between 30 and 60 and 47% had borderline and 53% moderate-to-marked LAD. Moderate-to-marked LAD group had higher frequencies of abnormal blood pressure (BP), FPG, and lipids than borderline LAD group even after conditioning effects of age and sex (p≤0.03) and of FPG after conditioning effects of BP (p=0.02). The frequencies of glucose intolerance were 48.9% even in borderline LAD with 84.9% in moderate-to-marked LAD group. In moderate-to-marked LAD group mean values of BP, FPG, and lipid profiles were higher (p<0.001) and abnormal. In borderline LAD group though mean BP and lipid values were normal, FPG was impaired. Conclusions: Impaired mean FPG values and high frequencies of glucose intolerance in both borderline LAD group with normal BP and moderate-to-marked LAD group with conditioning of effects of BP in relatively younger ambulatory adults without cardiac symptoms indicate possible association between LAD and glucose intolerance.
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