case study on anemia

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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

• Case report
• Open access
• Published: 13 September 2021

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.

Peer Review reports

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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DOI : https://doi.org/10.1186/s13256-021-03024-9

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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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• Published: 09 May 2024

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

• Kexue Ning 1 ,
• Xingyu Sun 2 ,
• Ling Liu 3 &
• Lijuan He 4  

Scientific Reports volume  14 , Article number:  10628 ( 2024 ) Cite this article

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• Public health
• Quality of life

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.

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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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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Momelotinib Improves Anemia in JAK Inhibitor-Naive Myelofibrosis

Compared with ruxolitinib, momelotinib improved mild, moderate, and severe anemia in patients with myelofibrosis who were naive to JAK inhibitors, according to the phase 3 SIMPLIFY-1 study.

Closeup 3D illustration of primary myelofibrosis (PMF) cells in blood flow: © LASZLO - stock.adobe.com

Treatment with momelotinib (Ojjaara) delivered benefits to anemia among patients with myelofibrosis who were naive to JAK inhibitors, regardless of their baseline hemoglobin level. Further, momelotinib provided significant anemia benefits compared with ruxoltinib (Jakafi), according to an analysis from the phase 3 SIMPLIFY-1 study (NCT01969838).

SIMPLIFY-3 randomized 432 patients with myelofibrosis who had not received JAK inhibitors toreceive momelotinib or ruxolitinib.In patients who were anemic and received momelotinib, mean hemoglobin levels increased by weeks 2 to 4 of treatment, and hemoglobin levels remained stable among patients who were not anemic.

Comparatively, patients who were anemic and nonanemictreated with ruxolitinib experienced an initial decrease in mean hemoglobin. This decrease stabilized after weeks 4 to 6 as patients received red blood cell transfusions. Patients receiving ruxolitinib were permitted to cross over to the momelotinib group, and mean hemoglobin levels increased after this change.

The study also evaluated patients at different levels of anemia. Among patient who were mildly anemic, with ahemoglobin levelbetween 10 and 12 g/dL, 90.4% of patients were transfusion-free at baseline, 93.9% of these patients remained transfusion-free while receiving momelotinib. Four patients who were not transfusion-free at baseline became transfusion-free while on treatment. In contrast, patients who were mildly anemic in the ruxolitinib arm became more dependent on transfusion; 50% of patients who were transfusion-free at baseline required a transfusion while on ruxolitinib.

“While treatment of mild anemia (hemoglobin levels of ≥10 to <12 g/dL) is not always routinely considered, our analysis also highlights the potential value of momelotinib in preserving transfusion independence in eligible patients with mild anemia for whom JAK inhibitor treatment is warranted,” authors of the study published in Leukemia & Lymphoma, wrote.

Regardingpatients who were not anemic, all those in the momelotinib arm were transfusion-free at baseline and remained so. Five patients who were transfusion-free at baseline in the ruxolitinib group required transfusions during treatment.

“While momelotinib demonstrated benefits across anemic subgroups, the impact of momelotinib in nonanemic patients is less clear.”

Among patients who were moderately or severely anemic, 34.1% were transfusion-free at baseline in the momelotinib group. Fourteen of the patients who required transfusions at baseline were able to become transfusion free, and 86.2% of those who were transfusion-free at baseline stayed so. In the ruxolitinib arm, only 30% of the moderately or severly anemic patients who were transfusion-free at baseline remained that way.

No new safety signals for momelotinib were identified. Discontinuation due to adverse events was more common in the moderate to severe anemic population receiving momelotinib (18.8%) compared with ruxolitinib (6.3%). However, dose reductions or interruptions were more common with ruxolitinib vs momelotinib (36.8% vs 21.2%, respectively).

“The clinical benefits and safety profile of momelotinib in JAK inhibitor-naive patients with myelofibrosis across mildly to severely anemic and nonanemic subgroups were generally consistent with those observed in the overall SIMPLIFY-1 trial population, thus representing a potential treatment option for patients with myelofibrosis regardless of baseline hemoglobin levels,” study authors concluded.

Gupta V, Oh S, DevosT,et al. Momelotinib vs. ruxolitinib in myelofibrosis patient subgroups by baseline hemoglobin levels in the SIMPLIFY-1 trial. Leuk Lymphoma.Published online March 19, 2024. doi:10.1080/10428194.2024.2328800

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Case Study: Sickle Cell Disease A 25-Year-Old in Transition

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A 25-year-old woman with a history of sickle cell disease (SCD) presents to the clinic for follow-up after a hospitalization for a vaso-occlusive pain crisis complicated by influenza A. She has a history of an acute ischemic stroke at age 5 years and has received monthly, simple red cell transfusions since the stroke. Her last transfusion was approximately four months prior. She is taking deferasirox 20 mg/kg daily but occasionally misses doses.

Laboratory results show the following:

Which of the following is the next best step in diagnosis

• Restart scheduled red blood cell transfusions
• Start prophylactic penicillin
• Discontinue transfusions and start hydroxyurea
• Order transcranial doppler ultrasonography (TCD) to assess risk of stroke
• Increase dose of deferasirox to 25 mg/kg/day

Explanation

The incidence of primary stroke in children with SCD is 0.6 to 0.8 events per 100 patient-years, with a cumulative incidence of 7.8 percent by age 14 years in the Jamaican cohort and 11 percent by age 20 years in the U.S. Cooperative Study of Sickle Cell Disease. Once stroke has occurred, the incidence of recurrent (secondary) stroke ranges from 47 to 93 percent in patients not started on regular transfusions. The Stroke Prevention Trial in SCD (STOP) randomized 130 high-risk children with SCD to either transfusion therapy (to maintain HbS 30%) or observation. These high-risk children had an increased blood flow in the internal carotid or middle cerebral artery by TCD. This study showed a 92 percent reduction in incidence of first stroke in transfused high-risk patients. A follow-up study, STOP2, randomly assigned 72 children whose TCD had normalized after 30 months of transfusion therapy to either ongoing or discontinued transfusions. The study was closed early due to a significant increase in abnormal TCD velocity and stroke risk for those who halted transfusion therapy.

The multicenter phase III TWiTCH trial evaluated children with SCA and abnormal TCD velocities without a history of stroke on chronic transfusions. Data showed that hydroxyurea at maximal tolerated dose was noninferior to chronic transfusions for maintaining TCD velocities as primary stroke prophylaxis (choice C). This patient has a history of ischemic stroke, so the results of TWiTCH do not apply to her.

The Stroke with Transfusions Changing to Hydroxyurea (SWiTCH) study was designed as a phase III multicenter trial to determine the efficacy of hydroxyurea/phlebotomy, compared with transfusions/chelation for children with SCA, stroke, and iron overload in secondary stroke prophylaxis. The primary endpoint was a composite of noninferiority for stroke prevention and superiority for reduction of liver iron content. The trial was terminated at the first scheduled interim analysis for futility for the composite endpoint, which required superiority of phlebotomy over iron chelation for reducing excess iron stores. The incidence of stroke on the hydroxyurea plus phlebotomy arm was higher (7 of 67 patients; 10.4%) than in the transfusion plus chelation arm (1 of 66 patients; 1.5%). These results, though not powered for inferiority, showed a trend towars increased stroke risk with transition to hydroxyurea. In patients with prior stroke, cessation of transfusion therapy is currently not recommended.

Whether chronic transfusion therapy can be stopped after a longer period of transfusions in a patient with a prior stroke remains unclear even though risk of recurrent stroke remains high in adolescence and young adulthood. In patients older than 16 years, TCD velocity criteria to determine stroke risk is not reliable (choice D).

In the Prophylaxis with Oral Penicillin in Children with Sickle Cell Anemia trial, children with SCA were randomly assigned to receive oral prophylactic penicillin or placebo PROPS 1986 ). The trial ended eight months early after the occurrence of 15 cases of pneumococcal sepsis, 13 in the placebo group and two in the penicillin group, showing an 84 percent reduction in pneumococcal sepsis with penicillin prophylaxis. The follow-up study, PROPS II, did not show an increased risk in pneumococcal infections with discontinuation of prophylactic penicillin after age 5 years. Therefore, prophylactic penicillin is not recommended in adults with SCA (choice B).

The trajectory of ferritin in this patient has not been established and an increase in oral iron chelation is not indicated at this time.

Case Study submitted by Marquita Nelson, MD, of University of Chicago, Chicago, IL.

• Hirst C, Owusu-Ofori S Prophylactic antibiotics for preventing pneumococcal infection in children with sickle cell disease . Cochrane Database Syst Rev. 2014 6:CD003427.
• Valadi N, Silva GS, Bowman LS, et al Transcranial Doppler ultrasonography in adults with sickle cell disease . Neurology. 2006 22:572-574.
• Ware RE, Davis BR, Schultz WH, et al Stroke with transfusions changing to hydroxyurea (SWiTCH) . Blood. 2012 119:3925-3932.
• Kumar N, Gross JB Jr, Ahlskog JE TCD with transfusions changing to hydroxyurea (TWiTCH): hydroxyurea therapy as an alternative to transfusions for primary stroke prevention in children with sickle cell anemia . Blood. 2015 126:3.

American Society of Hematology. (1). Case Study: Sickle Cell Disease A 25-Year-Old in Transition. Retrieved from https://www.hematology.org/education/trainees/fellows/case-studies/sickle-cell-disease-a-25-year-old-in-transition .

American Society of Hematology. "Case Study: Sickle Cell Disease A 25-Year-Old in Transition." Hematology.org. https://www.hematology.org/education/trainees/fellows/case-studies/sickle-cell-disease-a-25-year-old-in-transition (label-accessed May 09, 2024).

"American Society of Hematology." Case Study: Sickle Cell Disease A 25-Year-Old in Transition, 09 May. 2024 , https://www.hematology.org/education/trainees/fellows/case-studies/sickle-cell-disease-a-25-year-old-in-transition .

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