case study anaemia

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Critical iron deficiency anemia with record low hemoglobin: a case report

• Audrey L. Chai   ORCID: orcid.org/0000-0002-5009-0468 1 ,
• Owen Y. Huang 1 ,
• Rastko Rakočević 2 &
• Peter Chung 2  

Journal of Medical Case Reports volume  15 , Article number:  472 ( 2021 ) Cite this article

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Anemia is a serious global health problem that affects individuals of all ages but particularly women of reproductive age. Iron deficiency anemia is one of the most common causes of anemia seen in women, with menstruation being one of the leading causes. Excessive, prolonged, and irregular uterine bleeding, also known as menometrorrhagia, can lead to severe anemia. In this case report, we present a case of a premenopausal woman with menometrorrhagia leading to severe iron deficiency anemia with record low hemoglobin.

Case presentation

A 42-year-old Hispanic woman with no known past medical history presented with a chief complaint of increasing fatigue and dizziness for 2 weeks. Initial vitals revealed temperature of 36.1 °C, blood pressure 107/47 mmHg, heart rate 87 beats/minute, respiratory rate 17 breaths/minute, and oxygen saturation 100% on room air. She was fully alert and oriented without any neurological deficits. Physical examination was otherwise notable for findings typical of anemia, including: marked pallor with pale mucous membranes and conjunctiva, a systolic flow murmur, and koilonychia of her fingernails. Her initial laboratory results showed a critically low hemoglobin of 1.4 g/dL and severe iron deficiency. After further diagnostic workup, her profound anemia was likely attributed to a long history of menometrorrhagia, and her remarkably stable presentation was due to impressive, years-long compensation. Over the course of her hospital stay, she received blood transfusions and intravenous iron repletion. Her symptoms of fatigue and dizziness resolved by the end of her hospital course, and she returned to her baseline ambulatory and activity level upon discharge.

Conclusions

Critically low hemoglobin levels are typically associated with significant symptoms, physical examination findings, and hemodynamic instability. To our knowledge, this is the lowest recorded hemoglobin in a hemodynamically stable patient not requiring cardiac or supplemental oxygen support.

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Anemia and menometrorrhagia are common and co-occurring conditions in women of premenopausal age [ 1 , 2 ]. Analysis of the global anemia burden from 1990 to 2010 revealed that the prevalence of iron deficiency anemia, although declining every year, remained significantly high, affecting almost one in every five women [ 1 ]. Menstruation is considered largely responsible for the depletion of body iron stores in premenopausal women, and it has been estimated that the proportion of menstruating women in the USA who have minimal-to-absent iron reserves ranges from 20% to 65% [ 3 ]. Studies have quantified that a premenopausal woman’s iron storage levels could be approximately two to three times lower than those in a woman 10 years post-menopause [ 4 ]. Excessive and prolonged uterine bleeding that occurs at irregular and frequent intervals (menometrorrhagia) can be seen in almost a quarter of women who are 40–50 years old [ 2 ]. Women with menometrorrhagia usually bleed more than 80 mL, or 3 ounces, during a menstrual cycle and are therefore at greater risk for developing iron deficiency and iron deficiency anemia. Here, we report an unusual case of a 42-year-old woman with a long history of menometrorrhagia who presented with severe anemia and was found to have a record low hemoglobin level.

A 42-year-old Hispanic woman with no known past medical history presented to our emergency department with the chief complaint of increasing fatigue and dizziness for 2 weeks and mechanical fall at home on day of presentation.

On physical examination, she was afebrile (36.1 °C), blood pressure was 107/47 mmHg with a mean arterial pressure of 69 mmHg, heart rate was 87 beats per minute (bpm), respiratory rate was 17 breaths per minute, and oxygen saturation was 100% on room air. Her height was 143 cm and weight was 45 kg (body mass index 22). She was fully alert and oriented to person, place, time, and situation without any neurological deficits and was speaking in clear, full sentences. She had marked pallor with pale mucous membranes and conjunctiva. She had no palpable lymphadenopathy. She was breathing comfortably on room air and displayed no signs of shortness of breath. Her cardiac examination was notable for a grade 2 systolic flow murmur. Her abdominal examination was unremarkable without palpable masses. On musculoskeletal examination, her extremities were thin, and her fingernails demonstrated koilonychia (Fig. 1 ). She had full strength in lower and upper extremities bilaterally, even though she required assistance with ambulation secondary to weakness and used a wheelchair for mobility for 2 weeks prior to admission. She declined a pelvic examination. No bleeding was noted in any part of her physical examination.

Koilonychia, as seen in our patient above, is a nail disease commonly seen in hypochromic anemia, especially iron deficiency anemia, and refers to abnormally thin nails that have lost their convexity, becoming flat and sometimes concave in shape

She was admitted directly to the intensive care unit after her hemoglobin was found to be critically low at 1.4 g/dL on two consecutive measurements with an unclear etiology of blood loss at the time of presentation. Note that no intravenous fluids were administered prior to obtaining the hemoglobin levels. Upon collecting further history from the patient, she revealed that she has had a lifetime history of extremely heavy menstrual periods: Since menarche at the age of 10 years when her periods started, she has been having irregular menstruation, with periods occurring every 2–3 weeks, sometimes more often. She bled heavily for the entire 5–7 day duration of her periods; she quantified soaking at least seven heavy flow pads each day with bright red blood as well as large-sized blood clots. Since the age of 30 years, her periods had also become increasingly heavier, with intermittent bleeding in between cycles, stating that lately she bled for “half of the month.” She denied any other sources of bleeding.

Initial laboratory data are summarized in Table 1 . Her hemoglobin (Hgb) level was critically low at 1.4 g/dL on arrival, with a low mean corpuscular volume (MCV) of < 50.0 fL. Hematocrit was also critically low at 5.8%. Red blood cell distribution width (RDW) was elevated to 34.5%, and absolute reticulocyte count was elevated to 31 × 10 9 /L. Iron panel results were consistent with iron deficiency anemia, showing a low serum iron level of 9 μg/dL, elevated total iron-binding capacity (TIBC) of 441 μg/dL, low Fe Sat of 2%, and low ferritin of 4 ng/mL. Vitamin B12, folate, hemolysis labs [lactate dehydrogenase (LDH), haptoglobin, bilirubin], and disseminated intravascular coagulation (DIC) labs [prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, d -dimer] were all unremarkable. Platelet count was 232,000/mm 3 . Peripheral smear showed erythrocytes with marked microcytosis, anisocytosis, and hypochromia (Fig. 2 ). Of note, the patient did have a positive indirect antiglobulin test (IAT); however, she denied any history of pregnancy, prior transfusions, intravenous drug use, or intravenous immunoglobulin (IVIG). Her direct antiglobulin test (DAT) was negative.

A peripheral smear from the patient after receiving one packed red blood cell transfusion is shown. Small microcytic red blood cells are seen, many of which are hypochromic and have a large zone of pallor with a thin pink peripheral rim. A few characteristic poikilocytes (small elongated red cells also known as pencil cells) are also seen in addition to normal red blood cells (RBCs) likely from transfusion

A transvaginal ultrasound and endometrial biopsy were offered, but the patient declined. Instead, a computed tomography (CT) abdomen and pelvis with contrast was performed, which showed a 3.5-cm mass protruding into the endometrium, favored to represent an intracavitary submucosal leiomyoma (Fig. 3 ). Aside from her abnormal uterine bleeding (AUB), the patient was without any other significant personal history, family history, or lab abnormalities to explain her severe anemia.

Computed tomography (CT) of the abdomen and pelvis with contrast was obtained revealing an approximately 3.5 × 3.0 cm heterogeneously enhancing mass protruding into the endometrial canal favored to represent an intracavitary submucosal leiomyoma

The patient’s presenting symptoms of fatigue and dizziness are common and nonspecific symptoms with a wide range of etiologies. Based on her physical presentation—overall well-appearing nature with normal vital signs—as well as the duration of her symptoms, we focused our investigation on chronic subacute causes of fatigue and dizziness rather than acute medical causes. We initially considered a range of chronic medical conditions from cardiopulmonary to endocrinologic, metabolic, malignancy, rheumatologic, and neurological conditions, especially given her reported history of fall. However, once the patient’s lab work revealed a significantly abnormal complete blood count and iron panel, the direction of our workup shifted towards evaluating hematologic causes.

With such a critically low Hgb on presentation (1.4 g/dL), we evaluated for potential sources of blood loss and wanted to first rule out emergent, dangerous causes: the patient’s physical examination and reported history did not elicit any concern for traumatic hemorrhage or common gastrointestinal bleeding. She denied recent or current pregnancy. Her CT scan of abdomen and pelvis was unremarkable for any pathology other than a uterine fibroid. The microcytic nature of her anemia pointed away from nutritional deficiencies, and she lacked any other medical comorbidities such as alcohol use disorder, liver disease, or history of substance use. There was also no personal or family history of autoimmune disorders, and the patient denied any history of gastrointestinal or extraintestinal signs and/or symptoms concerning for absorptive disorders such as celiac disease. We also eliminated hemolytic causes of anemia as hemolysis labs were all normal. We considered the possibility of inherited or acquired bleeding disorders, but the patient denied any prior signs or symptoms of bleeding diatheses in her or her family. The patient’s reported history of menometrorrhagia led to the likely cause of her significant microcytic anemia as chronic blood loss from menstruation leading to iron deficiency.

Over the course of her 4-day hospital stay, she was transfused 5 units of packed red blood cells and received 2 g of intravenous iron dextran. Hematology and Gynecology were consulted, and the patient was administered a medroxyprogesterone (150 mg) intramuscular injection on hospital day 2. On hospital day 4, she was discharged home with follow-up plans. Her hemoglobin and hematocrit on discharge were 8.1 g/dL and 24.3%, respectively. Her symptoms of fatigue and dizziness had resolved, and she was back to her normal baseline ambulatory and activity level.

Discussion and conclusions

This patient presented with all the classic signs and symptoms of iron deficiency: anemia, fatigue, pallor, koilonychia, and labs revealing marked iron deficiency, microcytosis, elevated RDW, and low hemoglobin. To the best of our knowledge, this is the lowest recorded hemoglobin in an awake and alert patient breathing ambient air. There have been previous reports describing patients with critically low Hgb levels of < 2 g/dL: A case of a 21-year old woman with a history of long-lasting menorrhagia who presented with a Hgb of 1.7 g/dL was reported in 2013 [ 5 ]. This woman, although younger than our patient, was more hemodynamically unstable with a heart rate (HR) of 125 beats per minute. Her menorrhagia was also shorter lasting and presumably of larger volume, leading to this hemoglobin level. It is likely that her physiological regulatory mechanisms did not have a chance to fully compensate. A 29-year-old woman with celiac disease and bulimia nervosa was found to have a Hgb of 1.7 g/dL: she presented more dramatically with severe fatigue, abdominal pain and inability to stand or ambulate. She had a body mass index (BMI) of 15 along with other vitamin and micronutrient deficiencies, leading to a mixed picture of iron deficiency and non-iron deficiency anemia [ 6 ]. Both of these cases were of reproductive-age females; however, our patient was notably older (age difference of > 20 years) and had a longer period for physiologic adjustment and compensation.

Lower hemoglobin, though in the intraoperative setting, has also been reported in two cases—a patient undergoing cadaveric liver transplantation who suffered massive bleeding with associated hemodilution leading to a Hgb of 0.6 g/dL [ 7 ] and a patient with hemorrhagic shock and extreme hemodilution secondary to multiple stab wounds leading to a Hgb of 0.7 g/dL [ 8 ]. Both patients were hemodynamically unstable requiring inotropic and vasopressor support, had higher preoperative hemoglobin, and were resuscitated with large volumes of colloids and crystalloids leading to significant hemodilution. Both were intubated and received 100% supplemental oxygen, increasing both hemoglobin-bound and dissolved oxygen. Furthermore, it should be emphasized that the deep anesthesia and decreased body temperature in both these patients minimized oxygen consumption and increased the available oxygen in arterial blood [ 9 ].

Our case is remarkably unique with the lowest recorded hemoglobin not requiring cardiac or supplemental oxygen support. The patient was hemodynamically stable with a critically low hemoglobin likely due to chronic, decades-long iron deficiency anemia of blood loss. Confirmatory workup in the outpatient setting is ongoing. The degree of compensation our patient had undergone is impressive as she reported living a very active lifestyle prior to the onset of her symptoms (2 weeks prior to presentation), she routinely biked to work every day, and maintained a high level of daily physical activity without issue.

In addition, while the first priority during our patient’s hospital stay was treating her severe anemia, her education became an equally important component of her treatment plan. Our institution is the county hospital for the most populous county in the USA and serves as a safety-net hospital for many vulnerable populations, most of whom have low health literacy and a lack of awareness of when to seek care. This patient had been experiencing irregular menstrual periods for more than three decades and never sought care for her heavy bleeding. She, in fact, had not seen a primary care doctor for many years nor visited a gynecologist before. We emphasized the importance of close follow-up, self-monitoring of her symptoms, and risks with continued heavy bleeding. It is important to note that, despite the compensatory mechanisms, complications of chronic anemia left untreated are not minor and can negatively impact cardiovascular function, cause worsening of chronic conditions, and eventually lead to the development of multiorgan failure and even death [ 10 , 11 ].

Availability of data and materials

All data generated or analyzed during this study are included in this published article.

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Department of Medicine, University of Southern California, Los Angeles, CA, USA

Audrey L. Chai & Owen Y. Huang

Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Southern California, Los Angeles, CA, USA

Rastko Rakočević & Peter Chung

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AC, OH, RR, and PC managed the presented case. AC performed the literature search. AC, OH, and RR collected all data and images. AC and OH drafted the article. RR and PC provided critical revision of the article. All authors read and approved the final manuscript.

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Correspondence to Audrey L. Chai .

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Chai, A.L., Huang, O.Y., Rakočević, R. et al. Critical iron deficiency anemia with record low hemoglobin: a case report. J Med Case Reports 15 , 472 (2021). https://doi.org/10.1186/s13256-021-03024-9

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Patient Case Presentation

Patient  Overview

M.J. is a 25-year-old, African American female presenting to her PCP with complaints of fatigue, weakness, and shortness of breath with minimal activity. Her friends and family have told her she appears pale, and combined with her recent symptoms she has decided to get checked out. She also states that she has noticed her hair and fingernails becoming extremely thin and brittle, causing even more concern. The patient first started noticing these symptoms a few months ago and they have been getting progressively worse. Upon initial assessment, her mucosal membranes and conjunctivae are pale. She denies pain at this time, but describes an intermittent dry, soreness of her tongue.

Vital Signs:

Temperature – 37 C (98.8 F)

HR – 95

BP – 110/70 (83)

Lab Values:

Hgb- 7 g/dL

Serum Iron – 40 mcg/dL

Transferrin Saturation – 15%

Medical History

• Diagnosed with peptic ulcer disease at age 21 – controlled with PPI pharmacotherapy
• IUD placement 3 months ago – reports an increase in menstrual bleeding since placement

Surgical History

• No past surgical history reported

Family History

• Diagnosis of iron deficiency anemia at 24 years old during pregnancy with patient – on daily supplement
• Otherwise healthy
• Diagnosis of hypertension – controlled with diet and exercise
• No siblings

Social History

• Vegetarian – patient states she has been having weird cravings for ice cubes lately
• Living alone in an apartment close to work in a lower-income community
• Works full time at a clothing department store

• History of Present Illness

Review of Systems

• Past Medical History
• Physical Examination
• Differential Diagnosis
• Relevant Next Steps
• Test Results
• Interim Differential Diagnoses
• Relevant Next Steps 2
• Test Results 2
• Treatment Orders
• About the Case

Anemia in a 42-year-old woman

• General : Patient says she felt fine until about 2 months ago when she had "the flu," which she describes as a low-grade fever, diffuse joint pain, malaise, and a non-pruritic rash primarily over her extremities. She took acetaminophen and her symptoms resolved after 4 days. Except for her fatigue and dyspnea, she has since felt well with normal appetite and no fever or chills.
• Skin : No rash or lesions noted.
• HEENT : Denies pain or swelling in her neck, no nasal discharge or bleeding.
• Pulmonary : Dyspnea climbing stairs, worsening over the past 3 weeks to the point that she cannot climb a flight of steps without pausing to rest. No cough or wheezing.
• Cardiovascular : No exertional chest pain, palpitations, orthopnea, or paroxysmal nocturnal dyspnea.
• Gastrointestinal : No nausea, vomiting, diarrhea or abdominal pain.
• Genitourinary : Menses normal, last period 2 weeks prior, normal amount of bleeding for her. No other vaginal bleeding. Urination normal, no visible blood.
• Musculoskeletal : No swelling or pain in joints or extremities.
• Neurologic : Unremarkable
• Psychiatric : Unremarkable

• History of Present Illness
• Review of Systems
• Past Medical History
• Physical Examination

Differential Diagnosis

• Relevant Next Steps
• Test Results
• Interim Differential Diagnoses
• Relevant Next Steps 2
• Test Results 2
• Treatment Orders
• About the Case

Anemia in a 42-year-old woman

At this point, what causes of the patient's anemia CANNOT be excluded based on the findings of the history and physical examination and previous laboratory studies? (You may select more than one option.)

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Chapter 6-1:  Approach to the Patient with Anemia - Case 1

Jeremy Smith

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Chief complaint, constructing a differential diagnosis.

• RANKING THE DIFFERENTIAL DIAGNOSIS
• MAKING A DIAGNOSIS
• CASE RESOLUTION
• FOLLOW-UP OF MRS. A
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Mrs. A is a 48-year-old white woman who has had fatigue for 2 months due to anemia.

Figure 6-1.

Diagnostic approach: anemia.

Anemia can occur in isolation, or as a consequence of a process causing pancytopenia, the reduction of all 3 cell lines (white blood cells [WBCs], platelets, and red blood cells [RBCs]). This chapter focuses on the approach to isolated anemia, although a brief list of causes of pancytopenia appears in Figure 6-1 . The first step in determining the cause of anemia is to identify the general mechanism of the anemia and organize the mechanisms using a pathophysiologic framework:

Acute blood loss: this is generally clinically obvious.

Underproduction of RBCs by the bone marrow; chronic blood loss is included in this category because it leads to iron deficiency, which ultimately results in underproduction.

Increased destruction of RBCs, called hemolysis.

Signs of acute blood loss

Hypotension

Tachycardia

Large ecchymoses

Symptoms of acute blood loss

Hematemesis

Rectal bleeding

Vaginal bleeding

After excluding acute blood loss, the next pivotal step is to distinguish underproduction from hemolysis by checking the reticulocyte count:

Low or normal reticulocyte counts are seen in underproduction anemias.

High reticulocyte counts occur when the bone marrow is responding normally to blood loss; hemolysis; or replacement of iron, vitamin B 12 , or folate.

Reticulocyte measures include:

The reticulocyte count: the percentage of circulating RBCs that are reticulocytes (normally 0.5–1.5%).

The absolute reticulocyte count; the number of reticulocytes actually circulating, normally 25,000–75,000/mcL (multiply the percentage of reticulocytes by the total number of RBCs).

The reticulocyte production index (RPI)

Corrects the reticulocyte count for the degree of anemia and for the prolonged peripheral maturation of reticulocytes that occurs in anemia.

Normally, the first 3–3.5 days of reticulocyte maturation occurs in the bone marrow and the last 24 hours in the peripheral blood.

When the bone marrow is stimulated, reticulocytes are released prematurely, leading to longer maturation times in the periphery, and larger numbers of reticulocytes are present at any given time.

For an HCT of 25%, the peripheral blood maturation time is 2 days, and for an HCT of 15%, it is 2.5 days; the value of 2 is generally used in the RPI calculation.

The normal RPI is about 1.0.

However, in patients with anemia, RPI < 2.0 indicates underproduction; RPI > 2.0 indicates hemolysis or an adequate bone marrow response to acute blood loss or replacement of iron or vitamins.

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• Clinical Journal of Oncology Nursing
• Number 6 / December 2021

Autoimmune Hemolytic Anemia: A Case Study Presentation

Jessica Shelly

Michelle Kull

Autoimmune hemolytic anemia (AIHA) is a rare and potentially life-threatening condition. This article presents a case study of AIHA in a patient with a history of acute myelogenous leukemia in remission. Differentiating the cause and type of HA (extrinsic versus intrinsic) will be discussed, along with information on follow-up and refractory AIHA. Advanced practice RNs (APRNs) play an essential role in the early recognition of HA, as well as the diagnosis, referral, and management of the condition.

AT A GLANCE

• Unexplained normocytic or macrocytic anemia can be a sign of more serious conditions, such as AIHA. 
• APRNs are important to the recognition and prompt treatment of the potentially life-threatening complications of HA. 
• AIHA can often be managed with prednisone, but refractory cases may require additional treatment, such as immunotherapy or splenectomy. 

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Prevalence and contributing factors of anemia in patients with gynecological cancer: a retrospective cohort study

• Kexue Ning 1 ,
• Xingyu Sun 2 ,
• Ling Liu 3 &
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Scientific Reports volume  14 , Article number:  10628 ( 2024 ) Cite this article

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This retrospective cohort study aimed to determine the prevalence of anemia among patients with gynecological cancer prior to any treatment and to identify contributing factors associated with anemia in this group. We retrospectively analyzed data from female patients aged 18 and above, diagnosed with various forms of gynecological cancer at The Affiliated Hospital of Southwest Medical University between February 2016 and March 2021. Anemia was assessed based on the most recent CBC results before any cancer treatment. Eligibility was based on a definitive histopathological diagnosis. Key variables included demographic details, clinical characteristics, and blood counts, focusing on hemoglobin levels. Statistical analysis was conducted using logistic regression models, and anemia was defined as hemoglobin levels below 12 g/dL for women, according to WHO criteria. Of the 320 participants, a significant prevalence of anemia was found. Correlations between anemia and factors like age, educational level, and biological markers (iron, folic acid, and vitamin B12 levels) were identified. In our study, we found that the prevalence of anemia among patients with gynecological cancer prior to any treatment was 59.06%, indicating a significant health concern within this population. The study highlights a significant prevalence of anemia in patients with gynecological cancer, emphasizing the need for regular hemoglobin screening and individualized management. These findings suggest the importance of considering various characteristics and clinical variables in anemia management among this patient group. Further studies are needed to explore the long-term effects of these factors on patient outcomes and to develop targeted interventions.

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Introduction.

Anemia, a condition characterized by a deficient number of red blood cells or low hemoglobin levels, is a global health issue affecting both developing and developed countries 1 , 2 . It presents a particularly concerning comorbidity in patients with various cancers, including those diagnosed with gynecological malignancies. Its prevalence in cancer patients, especially those with solid tumors, is notably high, affecting about 30% to 90%. In patients with gynecological malignancies, this prevalence ranges from 26 to 85%. The etiology of anemia in these patients is complex, involving both tumor-specific factors and treatment-related elements, such as chronic inflammation and the suppression of erythropoietin production 3 . The presence of anemia in cancer patients is associated with reduced survival, decreased quality of life, and impaired response to treatment 4 , 5 , 6 .

Gynecological cancers, encompassing ovarian, cervical, and endometrial cancers, represent a significant portion of cancer diagnoses in women worldwide 7 . These malignancies are often accompanied by multiple complications, with anemia being a prevalent concurrent condition, potentially due to factors such as nutritional deficiencies, chronic bleeding, iron malabsorption, or treatment-related effects 8 . Despite its prevalence, the multifactorial etiology of anemia in gynecological cancer patients remains insufficiently explored, necessitating comprehensive studies to unravel the contributing factors and impact on clinical outcomes.

Several studies have underscored the negative implications of anemia on prognosis in cancer patients. Anemic cancer patients often exhibit diminished physical function, lower overall well-being, and reduced tolerance to cancer therapies, which can compromise treatment efficacy 9 . Furthermore, anemia has been associated with poorer prognosis and decreased survival rates in various cancer types 10 . In gynecological cancers, specifically, anemia prevalence has been reported to vary, influencing treatment decisions and outcomes 11 .

Managing anemia in patients with gynecological cancer is paramount, as correction of hemoglobin levels has been shown to improve treatment response, quality of life, and survival rates 12 . However, the heterogeneity in anemia's onset, severity, and etiological factors across different gynecological cancers complicates the formulation of uniform management strategies. This complexity underscores the need for a deeper understanding of anemia's prevalence, risk factors, and impact in the context of gynecological malignancies 13 .

Moreover, while the global burden of anemia has been extensively studied, there are geographical and demographic disparities in the available data 10 . Most existing research focuses on populations in high-income countries, with less known about anemia's characteristics in low- and middle-income regions 14 . These gaps highlight the necessity for localized studies that consider regional medical practices, demographic factors, and access to healthcare services (Fig.  1 ).

Study flowchart.

This study aims to fill these gaps by exploring the prevalence and risk factors of anemia among patients with gynecological cancers in a retrospective cohort. By analyzing demographic, clinical, and laboratory data, this research seeks to identify significant predictors of anemia in this population, contributing to more personalized and effective management strategies for affected patients. The findings are expected to provide healthcare professionals with insights to enhance anemia screening, prevention, and treatment measures in patients facing gynecological cancers, ultimately aiming to improve patient quality of life and survival outcomes.

Materials and Methods

Study design and participants.

This retrospective cohort study involved a carefully selected sample of 320 patients diagnosed with various forms of gynecological cancer, out of a larger pool of cases at The Affiliated Hospital of Southwest Medical University. The study spanned February 2016 to March 2021. Eligibility required female patients aged 18 or older with a confirmed histopathological diagnosis of gynecological cancer, including ovarian, cervical, and endometrial cancers. Comprehensive medical histories and records were essential for inclusion. Patients with severe concurrent diseases affecting hemoglobin levels, prior cancer treatments, or incomplete records were excluded. This selection ensured a focused analysis on the relationship between gynecological cancer and anemia.

Data collection

We reviewed detailed medical records to collect demographic, clinical, and laboratory data. This included age, marital status, economic status, education level, tumor type and stage, treatment history, and more. Laboratory data focused on hemoglobin levels, red blood cell count, and other relevant parameters. All data were anonymized to uphold ethical standards.

Outcome measures

Anemia prevalence, defined by WHO criteria (hemoglobin < 12 g/dL for women), was evaluated. Anemia status was determined from the latest CBC results before any cancer treatment, providing a baseline unaffected by treatment.

Statistical analysis

We employed descriptive statistics, univariate analysis, and multivariate logistic regression to identify anemia predictors, using SPSS software. A p-value < 0.05 was considered statistically significant.

Ethical considerations

The study was ethically approved, with informed consent waived due to its retrospective nature. All procedures complied with ethical standards and the Helsinki Declaration.

Ethical approval and consent to participate

This investigation was undertaken with the sanction of the Ethics Committee of The Affiliated Hospital of Southwest Medical University (Ethics code number: KY2023200) and an exemption for informed consent was obtained from the Ethics Committee of The Affiliated Hospital of Southwest Medical University due to retrospective nature of the study. All methods were conducted in compliance with relevant guidelines, regulations, and the Declaration of Helsinki.

Comparative analysis of demographic and clinical characteristics across overall cohort, non-anemic, and anemic patients with gynecological cancer

Table 1 presents a comprehensive comparative analysis of the demographic and clinical characteristics among the overall cohort, and distinctively between non-anemic and anemic patients diagnosed with gynecological cancer. The study encompassed a total of 320 patients, subdivided into 131 non-anemic and 189 anemic individuals based on predefined hemoglobin criteria. The median age for the entire cohort was 60 years, with a discernible age difference between non-anemic (median age 52 years) and anemic patients (median age 62 years), indicating a statistically significant association of older age with anemia (P < 0.001). Body weight and height measurements across the groups showed median values of 71 kg and 1.66 m, respectively, with no significant differences observed (Weight P = 0.492, Height P = 0.805). Similarly, Body Mass Index (BMI) comparisons revealed a median of 26.139 for the overall cohort, showing no significant difference between the non-anemic and anemic groups (P = 0.634). The distribution of marital status, economic status, and education level across the study population demonstrated a varied demographic profile with no significant differences in these socio-economic factors between non-anemic and anemic patients. This is highlighted by the comparable percentages across marital statuses and the slight variances in economic status and education levels that did not reach statistical significance. Clinically, hemoglobin levels displayed a marked difference, serving as the basis for distinguishing between anemic and non-anemic participants. The mean hemoglobin concentration was significantly lower in anemic patients (11.2 g/dL) compared to non-anemic patients (13.3 g/dL, P < 0.001). The analysis further explored red blood cell count, hematocrit, and mean cell volume, with no significant differences found between the two groups, emphasizing the specific impact of hemoglobin levels on anemia classification in this context. A closer look at biochemical markers revealed statistically significant lower levels of iron, folic acid, and vitamin B12 in anemic patients compared to non-anemic ones, underscoring the nutritional and metabolic factors contributing to anemia in this patient population. The types of tumors also showed a significant association with anemia prevalence, particularly noting a higher occurrence of cervical cancer among anemic patients, while the distribution of tumor stages and treatment history across both groups showed no statistical significance, indicating the inherent nature of anemia as a condition influencing the patient group regardless of cancer stage or treatment modality. In terms of reproductive health history, menstrual regularity and childbirth counts were considered, revealing no significant differences between the anemic and non-anemic groups, thus indicating the multifactorial causes of anemia beyond reproductive factors. The assessment of complications, medication history, nutrition intake, quality of life, and prognosis did not exhibit significant differences between the two groups, further emphasizing the complex interplay of factors contributing to anemia in patients with gynecological cancer.

Univariate and multivariate analyses of factors associated with anemia in patients with gynecological cancer

Table 2 presents a comprehensive analysis of the various factors potentially influencing the prevalence of anemia among the studied population. The multivariate analysis, which adjusts for potentially confounding variables identified in the univariate analysis, highlights several parameters with statistically significant associations with anemia. Age demonstrated a notable influence, with an odds ratio of 1.034, indicating that as the participants' age increased, so did the likelihood of anemia, a relationship that was statistically significant (P < 0.001). This finding underscores the importance of age as a factor in anemia prevalence. Interestingly, educational level emerged as another significant factor. Individuals with primary education levels were significantly more likely to experience anemia, with an odds ratio of 2.479 (P = 0.026), compared to those with secondary education levels. Furthermore, postgraduates showed an increased likelihood of anemia, with an odds ratio of 2.235, which was also statistically significant (P = 0.039). Several biological markers were prominently associated with anemia. Lower iron levels, lower folic acid levels, and lower vitamin B12 levels were all significantly associated with a higher likelihood of anemia, with P values of < 0.001, indicating strong statistical significance. These findings reinforce the known biological pathways of anemia, where deficiencies in these critical components often manifest in anemic symptoms. In terms of gynecological health, the type of tumor also influenced anemia prevalence. Specifically, individuals with cervical tumors were more likely to be anemic, with an odds ratio of 1.933, though this result bordered on statistical significance (P = 0.056). In contrast, several factors, including marital status, economic status, family history, and certain health markers (red blood cell count, hematocrit, mean cell volume), did not exhibit a significant association with anemia, underscoring the complexity of anemia's etiology. Overall, Table 2 elucidates the multifaceted nature of anemia's contributing factors, emphasizing the need for a holistic approach to patient assessment and treatment. By understanding these associations, healthcare professionals can better identify at-risk individuals and implement appropriate preventive and therapeutic measures.

This study illuminated several critical factors associated with anemia among patients with gynecological cancer, drawing attention to the intricate interplay between demographic, clinical, and socioeconomic variables. The findings underscore the necessity for a multifaceted approach to patient care, considering not only clinical symptoms but also the broader social determinants of health.

Age emerged as a significant predictor of anemia, with older patients exhibiting a higher likelihood of this condition. This trend aligns with existing research that has documented physiological changes related to aging, such as decreased bone marrow response and nutritional deficiencies, contributing to anemia's development 15 , 16 . Furthermore, older individuals often have comorbid conditions, complicating their clinical presentations 17 . Our study reinforces the importance of comprehensive geriatric assessments and tailored care strategies, acknowledging the unique physiological and social challenges this demographic faces.

The association between anemia and specific gynecological cancers, particularly cervical cancer, was a notable discovery. This outcome suggests that the biological characteristics of tumors, possibly related to their metabolic demands or cytokine-mediated systemic effects, play a role in modulating anemia risk 18 , 19 , 20 . These findings underscore the necessity for tumor-specific screening protocols and possibly differential management strategies, catering to the individualized needs of patients based on their cancer type.

Our study's revelation of the strong association between anemia and deficiencies in iron, folic acid, and vitamin B12 amplifies the conversation around holistic patient care. It's a reminder that clinical management should extend beyond treating cancer itself, encompassing aspects like nutritional counseling 21 . These deficiencies could be reflective of broader issues, including dietary habits, socioeconomic status, and even the impact of cancer therapies 22 . Incorporating nutritional assessments and interventions into patient care protocols could mitigate these risk factors, potentially improving treatment outcomes and quality of life.

The socioeconomic and educational disparities highlighted in our findings present a more systemic challenge. Lower educational levels correlated with higher anemia prevalence, potentially indicating gaps in health literacy, accessibility to healthcare resources, and overall health awareness 23 . This observation aligns with existing literature documenting health outcome disparities based on socioeconomic status 24 . It's a call to action for healthcare systems to adopt more inclusive strategies, ensuring that education, economic background, or social circumstances do not disadvantage patients in their healthcare journeys.

The insights gleaned from this study have several implications for clinical practice. They advocate for a more integrated approach to care, encompassing routine anemia screening, nutritional counseling, and targeted interventions for at-risk demographics. Furthermore, healthcare providers should be cognizant of the broader socioeconomic factors at play, advocating where possible for policy changes or support mechanisms to bridge these gaps.

It is crucial to acknowledge the role of our study's exclusion criteria, particularly the decision to omit patients with severe concurrent diseases known to affect hemoglobin levels. This choice was aimed at minimizing confounding factors and isolating the impact of gynecological cancers on anemia. However, this approach also means that the broader influence of comorbidities, such as chronic kidney disease, inflammatory diseases, and nutritional deficiencies, was not directly addressed within our analysis.

In reflecting upon the scope of our study, it is essential to acknowledge certain limitations that bear implications for the interpretation of our findings. The retrospective nature of our analysis, while offering a comprehensive overview, inherently limits our ability to infer causality between the incidence of anemia and gynecological cancers. Moreover, our examination did not extend into depth regarding lifestyle factors and other possible contributors to anemia, potentially overlooking significant determinants of its prevalence. A particularly noteworthy consideration is the variance in anemia prevalence across different stages of cervical cancer, which may be attributed to factors such as bleeding in advanced stages. This aspect was not delineated in our study, suggesting a pivotal area for subsequent research to explore the impact of cancer progression on anemia. Additionally, the homogeneity of our study population restricts the extrapolation of our findings to more diverse demographic groups. This limitation underscores the need for future research endeavors to embrace a broader demographic spectrum, thereby enhancing the generalizability and applicability of the findings. These considerations highlight the necessity for future studies to adopt a prospective design for establishing causality, delve deeper into the multifaceted contributors to anemia, and assess the influence of cancer staging on its prevalence, especially in the context of cervical cancer. By addressing these gaps, the research community can further enrich our understanding and management strategies for anemia in patients with gynecological cancer.

In addressing the crucial aspect of anemia prevalence among patients with gynecological cancers before the commencement of any treatment, our findings reveal a significant rate of 59.06%. This rate is particularly noteworthy in the context of the broader literature on the subject. For example, research conducted by Alghamdi et al. (2021) at King Abdulaziz Medical City, Jeddah, identified a prevalence rate of 90.7% among patients receiving active treatment, highlighting the impact of chemotherapy and radiotherapy on hemoglobin levels 11 . The difference between these rates underscores the importance of recognizing anemia as a pre-existing condition in a considerable proportion of gynecological cancer patients, which may be further exacerbated by the treatment process.

The distinction between pre-treatment and treatment-induced anemia emphasizes the necessity for early detection and management strategies tailored to address this condition from the point of cancer diagnosis. Integrating anemia management into the overall treatment plan for gynecological cancers is crucial, not only to improve patient quality of life but also potentially to enhance the efficacy of cancer treatment protocols.

Our study contributes to the growing body of evidence suggesting that anemia is a multifactorial issue in the context of gynecological cancers, with implications for both pre-treatment condition management and the monitoring of treatment-related side effects. It highlights the need for a proactive approach to anemia screening and intervention, ensuring comprehensive patient care that addresses all facets of this condition.

In conclusion, this study underscores the multifactorial nature of anemia in patients with gynecological cancer, highlighting the influence of demographic, tumor-specific, nutritional, and socioeconomic factors. The findings advocate for an integrated, patient-centered approach to care, sensitive to the various challenges patients may face in their healthcare journeys. As we move forward, a commitment to continual research and an embrace of holistic care strategies will be paramount in enhancing patient outcomes and quality of life.

Dara availability

The datasets analyzed during the current study are not publicly available due to privacy but are available from the corresponding author at a reasonable request.

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Acknowledgements

We would like to express our sincere gratitude to all individuals who contributed to the completion of this study. This study followed the EQUATOR network guidelines.

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Department of Gynecology, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, Sichuan, China

Department of Reproductive Medicine Center, The Affiliated Hospital, Southwest Medical University, 25 Taiping Street, Luzhou, China

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Ling Liu designed the study, analyzed the data, and drafted the manuscript. Xingyu Sun and Kexue Ning participated in the critical discussion and revision of the article. Lijuan He assisted in the article writing and revising. The authors contributed to the article and approved the submitted version.

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Ning, K., Sun, X., Liu, L. et al. Prevalence and contributing factors of anemia in patients with gynecological cancer: a retrospective cohort study. Sci Rep 14 , 10628 (2024). https://doi.org/10.1038/s41598-024-61015-4

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Case Study: 44-Year-Old Man with Fever, Abdominal Pain, and Pancytopenia

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A 44-year-old man presents with fever, abdominal pain, and fatigue. His physical examination shows splenomegaly. His laboratory results are as follows:

The patient is transfused several units of packed red blood cells without significant correction of his anemia, and instead, his pancytopenia worsens. Peripheral smear shows pancytopenia without blasts, tear drop cells, or dysplasia. A bone marrow biopsy demonstrates the following:

• Aplastic anemia
• Acute promyelocytic leukemia
• Myelofibrosis
• Hemophagocytic lymphohistiocytosis
• Myelodysplastic syndrome

Explanation

The most likely diagnosis is hemophagocytic lymphohistiocytosis (HLH). The patient fulfills at least five of the main nine diagnostic criteria of HLH including fever, splenomegaly, cytopenia, elevated ferritin, low fibrinogen, and evidence of hemophagcytosis on bone marrow, as demonstrated in the pictures that a histiocytes engulfing a nucleated red cell (Figure 1) and a neutrophil (Figure 2).

Myelofibrosis can be associated with splenomegaly, but is less likely here since no marrow fibrosis or tear drop cells reported. Myelodysplastic syndrome is a possible cause of pancytopenia, but no dysplasia was noted on peripheral smear or in the bone marrow. Acute promyelocytic leukemia can be associated with DIC and low fibrinogen on presentation, but should have a hypercellular bone marrow with predominance of promyelocytes. Patients with aplastic anemia are found to have profound hypocellular bone marrow, but no hemophagocytes should be found.

Case study submitted by Tzu-Fei Wang, MD, The Ohio State University, Columbus, OH

American Society of Hematology. (1). Case Study: 44-Year-Old Man with Fever, Abdominal Pain, and Pancytopenia. Retrieved from https://www.hematology.org/education/trainees/fellows/case-studies/male-fever-abdominal-pain-pancytopenia .

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A case of pernicious anemia requiring differential diagnosis of autoimmune hemolytic anemia complication

1 Department of Hematology and Oncology, Kita-Harima Medical Center, Hyogo, Japan

Kohei Okamoto

2 Department of Nephrology, Kita-Harima Medical Center, Hyogo, Japan

Takeshi Sugimoto

Toshimasa takahashi.

3 Department of Diabetes and Endocrinology, Kita-Harima Medical Center, Hyogo, Japan

Yasushi Nakagawa

Takashi arai, katsuhito nishiyama.

4 Department of General and Geriatric Internal Medicine, Kita-Harima Medical Center, Hyogo, Japan

Yoshiro Yasutomo

Koichi yokono.

An 80-year-old female was admitted to our hospital due to malaise. The initial diagnosis on admission was pernicious anemia (PA), Hashimoto thyroiditis and autoimmune atrophic gastritis. Autoimmune hemolytic anemia was suspected because direct antiglobulin test (DAT) was positive. Treatment with vitamin B12 improved anemia, with the disappearance of hemolysis. In some cases, PA patients with positive DAT may have hemolysis without the involvement of the autoimmune mechanism. Therefore, it is important to carefully assess PA patients with hemolysis and positive DAT for the prevention of unnecessary administration of steroid therapy.

INTRODUCTION

Pernicious anemia (PA) is a megaloblastic anemia caused by the deficiency of vitamin B12 (cobalamin). Vitamin B12 (Vit.B12) is a crucial vitamin for DNA synthesis. Vit.B12 is absorbed in the terminal ileum as a complex with intrinsic factor, secreted by parietal cells of the stomach. In PA, intrinsic factor antibodies inhibit the absorption of Vit.B12 in the ileum by obstructing intrinsic factor binding to Vit.B12. Additionally, parietal cell antibodies, linked to atrophic gastritis, are present in PA. Parietal cell antibodies destroy parietal cells, subsequently resulting in the loss of intrinsic factor produced by parietal cells. Autoimmune atrophic gastritis is caused by this autoimmune reaction by parietal cell antibodies. In some cases, PA is associated with other autoimmune diseases such as Hashimoto thyroiditis, primary biliary cirrhosis or autoimmune hepatitis. Moreover, PA may be associated with the production of red blood cell (RBC) antibodies [ 1 ], leading to autoimmune hemolytic anemia (AIHA). Previous studies have reported PA with a positive direct antiglobulin test (DAT). However, a differential diagnosis of AIHA with positive DAT, in which autoimmune hemolysis has not occurred, is difficult in the early phases of disease. In this article, a case of PA requiring differential diagnosis of AIHA complication is presented.

CASE PRESENTATION

An 80-year-old female was admitted to the outpatient clinic in our hospital. The patient’s chief complaint was malaise lasting ~1 month prior to hospital admission. The patient had a medical history of Hashimoto thyroiditis from the age of 62 years, and osteoporosis was detected at the age of 67 years. No appreciable disease was reported in the patient’s familial medical history. The patient did not show an allergic tendency to drugs, nor medical preference about smoking and alcohol drinking. The patient was prescribed with levothyroxine (100 μg/day) and risedronate sodium (2.5 mg/day).

Physical examination revealed normal vital signs, and height of 158 cm and weight of 52.5 kg. The patient presented with generalized pallor including anemic conjunctiva, jaundice on the face and bulbar conjunctiva, slightly swollen thyroid gland, jugular venous distention and leg edema. Blood count test revealed the following: hemoglobin (Hb) 3.7 g/dl; mean corpuscular volume (MCV) 125.5 fL; platelet count 94 × 10 9 /μl; and macrocytic anemia. Serological test revealed the following abnormalities: lactate dehydrogenase (LD) 3612 IU/l (normal range 119–229) with a high percentage of LD1 and LD2 isozyme; indirect bilirubin (I-Bil) 2.48 mg/dl; and haptoglobin (Hpt) < 10 mg/dl, indicating hemolysis. Vit.B12 was below the detection sensitivity level. Immunological test revealed the elevation of thyroglobulin antibodies (Tg Ab) and thyroid peroxidase antibodies (TPO Ab) to >4000 mg/dl and 397 IU/ml, respectively. Gastric parietal cell antibodies and intrinsic factor antibodies were positive. DAT (direct Coombs test) was positive [Table ​ [Table1]. 1 ]. Monospecific DAT test with anti-IgG was positive (1+), and same test with anti-C3d was negative. Indirect antiglobulin test (IAT) was negative. Chest X-ray revealed 60% of cardiothoracic ratio and bilateral pleural effusions. Examination with upper gastrointestinal endoscopy revealed atrophic gastritis. Bone marrow aspiration testing identified hypercellular bone marrow and abnormal erythroblast carrying megaloblastic change and abnormality of nuclear division [Fig. ​ [Fig.1A 1 A and B]. Based on the presence of Vit.B12 deficiency, and positivity of gastric parietal cell antibodies and intrinsic factor antibodies this macrocytic anemia case was diagnosed as PA [ 2 , 3 ]. This case fulfills the domestic (Japanese) diagnostic criteria for hemolytic anemia, i.e. anemia, jaundice, decrease in Hpt level, increase in indirect bilirubin and urinary urobilinogen levels, and increased erythroblast (immature RBC) count in the bone marrow [ 4 ]. In addition, this DAT positive case has the possibility of complicating AIHA by domestic criteria [ 4 ]. The initial diagnosis of this patient included PA, Hashimoto thyroiditis, autoimmune atrophic gastritis and suspected AIHA at the time of admission to the hospital.

Laboratory data on admission

Reti, Reticulocyte; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin; AST, aspartate aminotransferase; ALT, alanine aminotransferase; BUN, blood urea nitrogen; CRP, C-reactive protein; Ab, Antibodies; TPO, thyroid peroxidase; PAIgG, platelet associated immunoglobulin G; ADAMTS-13, a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13; HS-PNH cells, high sensitivity paroxymal nocturnal hemoglobinuria type cells.

Bone marrow aspiration test at admission. ( A ) (×40) Hypercellular marrow. ( B ) (×400) Erythroblast revealed megaloblastic change and abnormality of nuclear division (arrow). ( C ) Bone marrow aspiration test 3 weeks after initiating Vit.B12 administration. Erythroblast decreased and attained its normal size (arrow).

Figure ​ Figure2 2 indicates the clinical course of this case. Shortly after admission (Day 1), the patient received 2 units of RBC. Muscle injection of 1 mg of Vit.B12 (methylcobalamin) was initiated thrice weekly for the first 3 weeks, followed by once weekly up to 2 months from the time of admission. The cause of hemolytic anemia was unclear, and therefore, immunosuppressive therapy using steroids was not administered. Hb levels were monitored and the time of steroid treatment initiation, in case of ineffective Vit.B12 therapy, was recorded. Sodium ferrous citrate (100 mg/day) was orally administered from Days 7 to 28 to prevent iron insufficiency. This intervention resulted in a gradual improvement of Hb levels. Bone marrow reexamination, performed on Day 22, indicated the disappearance of megaloblastic change in erythroblast [Fig. ​ [Fig.1C]. 1 C]. The patient was discharged and followed the outpatient clinic after treatment Day 23. The hemolytic signs including the decrease in Hpt level or the abnormality of MCV had disappeared. DAT was negative on treatment Day 7, and additional DAT test on Days 11 and 25 remained negative. Therefore, it was concluded that this hemolytic anemia was not the result of an autoimmune hemolytic condition, but rather caused by PA. Five months after starting therapy, the Hb level increased to 10.5 mg/dl.

Clinical course.

Autoimmune polyglandular syndrome (APS) is characterized by numerous features of autoimmune diseases. APS is defined as sequential or simultaneous deficiencies in the function of several endocrine organs, and it is classified into three types based on the combination of endocrine deficiency [ 5 , 6 ]. APS Type III is characterized by autoimmune thyroiditis and other types of autoimmune disease without Addison’s disease. This patient was classified as having APS Type IIIb, in which Hashimoto thyroiditis, autoimmune atrophic gastritis, and PA are combined. Complication of AIHA usually observed in APS IIIc was also suspected in the initial stage of the clinical course due to positive DAT.

PA with positive DAT status is associated with the appearance of hemolysis [ 1 , 7 – 9 ]. The autoantibody produced in PA patients may usually have non-specific reaction with erythrocyte. However, in some cases, autoantibody affects hemolytic reaction to erythrocyte [ 7 , 8 ]; in which anemia will be persist with Vit.B12 treatment itself. PA has the status of ineffective erythropoiesis, where most of erythroblasts are dying in the intramedullary area by apoptosis, and release LDH [ 10 ]. The ‘hemolysis’ in PA is not the same status as that of AIHA; where hemolysis occurs on intra-vascular or extra-vascular area. Because the feature or laboratory data is similar between PA and AIHA, we express the hemolytic feature of PA as ‘hemolysis’ in this article. In this connection, serum LD level is known to be elevated generally [ 11 ], and one study showed LD was elevated in 80.4% of PA cases [ 12 ]. In this condition, it is clinically important to determine the involvement of AIHA in the occurrence of hemolysis. Previous reports were divided into the following three groups: (a) positive DAT status changed to negative after Vit.B12 therapy with improving anemia, (b) positive DAT status changed to negative after Vit.B12 and steroid therapy with improving anemia, (c) positive DAT status was maintained after Vit.B12 and steroid therapy with improving anemia. PA cases with positive DAT status did not receive stereotyped therapy and DAT status after treatment remains positive in some cases, regardless of anemia improvement. Our presenting case is suited to group (a), and similar two cases [ 1 ] and another single case [ 9 ] are included in this group. Yeruva et al. reviewed 14 middle-aged or elderly female PA patients with AIHA complication, involving other autoimmune diseases such as systemic lupus erythematosus (SLE) [ 13 ]. According to the 2012, Systemic Lupus International Collaborating Clinics (SLICC) classification criteria, positive DAT status is an independent factor in the judgment of immunological status irrespective of the existence of hemolytic anemia [ 14 ]. In above criteria, SLE patients with positive DAT status do not develop autoimmune hemolytic condition. Because most PA patients have hemolysis owing to ineffective erythropoiesis, PA patients complicated with SLE may have non-autoimmune-mediated hemolysis. Hence, it may be difficult to determine the cause of hemolysis (autoimmune or non-autoimmune mechanism) in PA patients complicated with SLE.

Rabinowitz et al. classified these PA patients with positive DAT status into 2 groups: (a) hemolysis by autoimmune-mediated reaction and (b) hemolysis with non-autoimmune-mediated reaction [ 15 ]. The former group shows continuous positive DAT status, whereas the latter group shows inverted negative DAT status after PA treatment. It is speculated that the case discussed in this article can be classified in the latter group due to the change of DAT status from positive to negative with the improvement of anemia by Vit.B12 treatment only. In this case, anemia is mainly caused by the malabsorption of Vit.B12 as a result of the presence of intrinsic and parietal cell antibodies without the complication of AIHA. The deficiency of Vit.B12 levels leads to the inhibition of DNA synthesis, which consequently results in immature and ineffective erythropoiesis. The positive DAT status in this case may be derived from non-specific autoantibody, because it turned negative after Vit.B12 treatment. The mechanism of producing non-specific autoantibody is not clear. It is known that autoantibody classified as IgG is more bound on older erythrocyte than younger erythrocyte [ 16 ]. A hypothesis is that the decrease of producing newly erythrocyte by ineffective erythropoiesis on PA patients leads to the increase of older erythrocyte; the erythrocyte will increase the number of binding IgG antibody as a consequence. To conclude, PA patients with positive DAT status may have hemolysis without the involvement of the autoimmune mechanism. Therefore, it is important to carefully assess PA patients with hemolysis and positive DAT status for the prevention of unnecessary administration of steroid therapy.

ACKNOWLEDGEMENTS

The authors would like to thank Enago ( www.enago.jp ), and Dr Man-I M (Kita-Harima Medical Center) for the English language review.

CONFLICT OF INTEREST STATEMENT

None declared.

There was no funding for this report.

ETHICAL APPROVAL

No ethical approval required.

Informed consent has been taken from the patient herself.

Dr Takeshi Sugimoto.

Aplastic Anemia: How it impacts a patient’s life

A plastic anemia, or bone marrow failure, is a rare and severe condition in which the human body stops producing enough new blood cells. Although the exact incidence of this condition is unknown, a study reported that there are close to 1.6 cases per million people annually worldwide.

Moreover, there is no significant reason for developing this disease, but it occurs when one’s immune system starts attacking the bone marrow, disrupting the production of cells. Aplastic anemia occurs when stem cells are damaged, resulting in either an empty bone marrow (aplastic) or a few blood cells in the bone marrow (hypoplastic). In this article, we will discuss in depth the causes, symptoms, diagnosis, and treatment of this rare blood disease.

What are the causes and symptoms of aplastic anemia?

Some of the estimated causes of aplastic anemia include autoimmune diseases, viral infections, paroxysmal nocturnal hemoglobinuria, pregnancy, and inherited bone marrow failure syndromes. That is not all - this disease has also been linked to some inherited conditions, including Fanconi Anemia, Dyskeratosis congenita, Shwachman-Diamond syndrome, Diamond-Blackfan Anaemia, and Pearson syndrome. Since these conditions primarily affect one’s bone marrow and other body parts, aplastic anemia may also occur in these patients.

While this kind of anemia has no distinctive symptoms, sure signs may include frequent viral infections, fatigue, bruising, shortness of breath, paler skin color, dizziness, headache, and fever. These signs may mimic other less severe illnesses, so consultation becomes necessary if one has been sick for several weeks and feels fatigued.

What are the diagnosis and treatments for aplastic anemia?

According to Dr. Rahul Bhargava, Principal Director of Hematology and Bone Marrow Transplant, Fortis Memorial Research Institute, Gurugram, “Aplastic anemia is diagnosed through physical examinations, blood tests, and genetic tests. These may include a complete blood count (CBC), peripheral blood smear, reticulocyte count, and bone marrow aspiration and biopsy. Further, the treatment plan may vary depending on the patient's situation because some people may sometimes develop this disease due to the treatment they’re receiving for cancer or other autoimmune diseases. In such cases, a change of therapy can be beneficial.”

On the other hand, moderate cases of aplastic anemia may be diagnosed if blood cell levels are lower than average and without visible symptoms. In this case, monitoring overall health and blood counts can address the concern, as it is vital to ensure that the case does not worsen.

In severe cases of aplastic anemia, treatments may include using immunosuppressants to keep the immune system from attacking stem cells. Additionally, blood transfusions may help ease symptoms by replacing red blood cells and platelets, while antibiotics may help treat and combat infections. Lastly, allogeneic stem cell transplantation may also help, wherein the damaged stem cells are replaced with healthy ones from donated blood or bone marrow.

How does aplastic anemia impact a patient’s life?

Aplastic anemia significantly impacts a patient's life in various ways. Since weakness and fatigue are common among such patients, they cannot carry out daily activities. The increased risk of infections and bleeding necessitates frequent medical interventions, including hospitalizations and blood transfusions, disrupting regular routines. They also face a lot of emotional challenges, including anxiety and depression, due to the chronic nature of the disease and its impact on quality of life.

Additionally, managing aplastic anemia often requires ongoing medical care, including regular monitoring and potentially intensive treatments such as immunosuppressive therapy or bone marrow transplantation. In other words, aplastic anemia imposes significant physical, emotional, and practical burdens on patients, necessitating comprehensive support and management strategies.

READ ALSO: How techies helped stop 45 births with blood disorders

What are the lifestyle changes and precautions for patients with aplastic anemia?

Aplastic anemia can be managed by following a treatment plan and monitoring symptoms. To prevent excessive bleeding, one must avoid high-contact activities and sports like football, hockey, or wrestling. Incorporating proper hygiene practices and getting vaccinations can help one protect themselves from contracting the disease through viruses and germs. Further, getting sufficient rest is also essential for patients with aplastic anemia because they are more likely to feel weakness, breathlessness, and tiredness. Finally, consulting a nutritionist to guide meal planning and eating a healthy diet can also help boost energy.

The success rate for treating aplastic anemia stands around 80 percent, with the cost remaining relatively low. While the disease is highly alarming for the victim and the family of the person who develops this condition, if diagnosed on time, one can fight this disease and live a healthy and fulfilling life.

READ ALSO: Siblings overcome thalassemia odds with half-match marrow transplant

What is the outlook for patients with this condition?

Aplastic anemia's survival depends on age, disease severity, and initial therapy response. Patients who recover after drug cessation or treatment of underlying conditions have stable clinical courses. According to data, the five-year survival for such patients is over 75 percent for patients undergoing bone marrow transplants. However, if this condition is untreated, patients do not survive beyond a year as they are at a high risk of dying from related complications like bleeding, infections, or lymphoproliferative disorders.

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Racism simmered in a Texas school district. Culture war made it boil.

Journalist Mike Hixenbaugh’s book “They Came for the Schools” is a propulsive account of the controversies that swept through a North Texas suburb.

The December of my senior year in high school, I sat in a biology class taught by a teacher who had just written me a letter of recommendation for my college applications. We were reviewing for final exams when the subject of genetic diseases came up. A consummate overachiever, I raised my hand to ask a question that hadn’t been covered in the material we’d been given.

“Why are Black people more likely to be born with sickle cell anemia?”

My teacher replied, “Karma.”

It was clearly intended as a joke, and after six years in Texas spent inuring myself to the sting of such comments, I took it as such. He answered my question in earnest, and we moved on to another topic. Later that night, I recorded the interaction on my Tumblr, where I tagged it with “ my life” and “funny as hell.” Sometimes I wonder what might have happened if I hadn’t — if that moment would have faded, sun-bleached like the rest of my recollections of my Black Texan adolescence.

Instead, that moment returned unbidden as I read Mike Hixenbaugh’s “ They Came for the Schools: One Town’s Fight Over Race and Identity, and the New War for America’s Classrooms .” Hixenbaugh, along with his NBC colleague Antonia Hylton , was among the first journalists to take note of the battle fomenting in Southlake, an ostensibly idyllic North Texas suburb. This razor-sharp book is the masterful culmination of years of reportage.

Over the course of 16 propulsive chapters, Hixenbaugh lays bare the journey that took Carroll Independent School District from one of the most highly lauded public school districts in the nation to one now facing eight civil rights complaints. The U.S. Department of Education is negotiating with Carroll ISD over four of those complaints, which, as Hixenbaugh recently reported , “signals that the department has substantiated the students’ allegations of racist and anti-LGBTQ discrimination.”

The controversy began, as most do these days, on social media. In 2018, a video of White high school students from Southlake chanting the n-word went viral. The video was recorded on the night of a homecoming dance at which students reported hearing “all these white kids just jumping up and down screaming slurs.” The video became a source of embarrassment for the town, and residents hoped it would blow over quickly. But when the school board called a special meeting to allow members of the community to express their feelings, it became abundantly clear that wouldn’t be the case.

“One after another that morning, parents of Black students came forward with painful stories of their own — like a dam had broken under the weight of decades worth of unaddressed grievances,” Hixenbaugh writes. “By the end of the meeting, many in attendance were in tears, including some white parents.”

In a move that would come to seem inconceivable just three years later, the district, along with a board of volunteers, came up with what they called the Cultural Competence Action Plan. It was released in the summer of 2020, just a few short months after students organized a protest at Southlake Town Square in the wake of George Floyd’s murder. The CCAP called for “mandatory cultural sensitivity training for all Carroll students and teachers; a top-to-bottom review of district curricula to embed culturally responsive lessons at every grade level; a formal process for reporting and tracking incidents of racist bullying; an audit to ensure student clubs were welcoming and inclusive regardless of race, gender, or sexuality; the creation of a new LGBTQ focus group to foster dialogue at the high school; and changes to the code of conduct to more explicitly spell out consequences for acts of discrimination.”

In the midst of a post-George Floyd racial backlash , the CCAP, Hixenbaugh writes, “landed like a bomb.”

From here, the story takes on a shape now familiar after three years of conservative reaction against “critical race theory” and “gender ideology” in public school classrooms. A murderer’s row of the conservative right’s favorite culture warriors made appearances in the ensuing conflict that Hixenbaugh methodically documents, including Southlake resident Dana Loesch, Tucker Carlson, Chris Rufo and Ron DeSantis .

But Hixenbaugh also spotlights lesser-known figures like Leigh Wambsganss, the wife of a former Southlake mayor and a co-founder of the Southlake Families political action committee, which promised to defeat the CCAP. With a war chest of nearly a quarter-million dollars and a slate of handpicked hard-line conservative school board candidates, Southlake Families developed a strategy that would soon be replicated across the country.

According to Hixenbaugh, nearly a dozen local PACs were formed in the Dallas-Fort Worth suburbs in 2021 alone — “so many that a liberal Fort Worth newspaper coined the phrase ‘the Southlake Playbook’ to describe the surge of conservative organizing around local nonpartisan school boards.”

The public high school I attended is a 15-minute drive from Southlake. My parents still live in the area and occasionally shop at a Trader Joe’s a stone’s throw from the town square where Southlake students chanted: “Say his name! George Floyd!” Hixenbaugh briefly mentions a private school my parents considered when my family first made our move from Chicago to North Texas. My mother recently told me that the school wanted to hold me back a grade. She was confused, or perhaps insulted, given that the elementary school I had previously attended had instead allowed me to skip fifth grade. Hixenbaugh writes that in 1972, that same school’s headmaster told the Associated Press, “We have had some Blacks apply from the area but the pathetic situation is that they cannot make the preliminary testing.”

“They Came for the Schools” is full of private ghosts like these, phantasmic half-images of my Texas education, rendered in spare prose. Describing what he calls “a common example” of a microaggression at Carroll, for example, Hixenbaugh alludes to “a white student telling an academically gifted Black classmate that she’s ‘the whitest Black girl I know.’”

There’s a specificity in the racism that’s as native to Texas as bluebonnets. It’s perfectly captured in that refrain, which is most often, in my experience, deployed as a compliment. That strain of racism makes room for what Lawrence Wright once described as the “cowboy individualism” that the state was founded on. It allows individuals to escape the overt malice of racial terror, as long as they simultaneously subvert the stereotypes — and divest from the communities — they are measured against.

The school where the n-word sat so comfortably in my White classmates’ mouths is the same school that performs a haka, a Tongan ritual from the other side of the world, before every football game . In a way, it’s the bastardized fulfillment of the promise of the American melting pot. We will take what serves us and demand you leave the rest behind. The cognitive dissonance this creates is as jarring as the slurs.

The nature of that racism, of that dissonance, might address one of the only questions that Hixenbaugh leaves unanswered: How did neighbor so quickly turn on neighbor? How did a town go from openly admitting to and promising to rectify its history of racial discrimination to suggesting that anyone who attempted to do so was a traitor to their country? And perhaps, most important, can that process be reversed? Not without outside guidance, if the Education Department’s recent intervention into Southlake Carroll is anything to go by.

All the Southlake students who filed complaints with the Education Department have already graduated. It’s unclear how many other children’s high school years will be shaped by these same traumas, how many of them will be subject to refrains that are far too familiar to older ears.

But perhaps here too Hixenbaugh can be instructive. At its core “They Came for the Schools” is a work of compassion, one that never fails to center the vulnerability or the dignity of students like Mia Mariani. One of the students whose civil rights complaints formed the basis of the recent negotiations between Carroll ISD and the Education Department, Miriani said she was surprised that her concerns had attracted official attention. “She’s worked to move on from her experiences in Southlake,” Hixenbaugh wrote, “but hopes her case leads to changes for current and future students.”

“Any change for them,” Mariani told him, “is healing for me.”

Rachelle Hampton is a culture writer for Slate and host of the internet culture podcast “In Case You Missed It.”

They Came for the Schools

One Town’s Fight Over Race and Identity, and the New War for America’s Classrooms

By Mike Hixenbaugh

Mariner. 288 pp. $32.50

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