What are the causes of anemia with normal Lactate Dehydrogenase (LDH) levels?

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From the Guidelines

Anemia with normal Lactate Dehydrogenase (LDH) levels is most likely caused by iron deficiency anemia, anemia of chronic disease, or other non-hemolytic conditions. The causes of anemia can be classified based on the mean corpuscular volume (MCV) and reticulocyte count.

  • Microcytic anemia with normal or low reticulocytes can be caused by iron deficiency, anemia of chronic disease, lead poisoning, or hereditary microcytic anemia 1.
  • Normocytic anemia with normal or low reticulocytes can be caused by acute hemorrhage, renal anemia, anemia of chronic disease, severe aplastic anemia, or primary bone marrow diseases 1.
  • Macrocytic anemia with normal or low reticulocytes can be caused by myelodysplastic syndrome, vitamin B12 deficiency, folate deficiency, long-term cytostatic medication, hypothyroidism, or alcoholism 1. It is essential to evaluate the underlying cause of anemia, as it may be related to blood loss, malabsorption, or inadequate dietary intake.
  • Laboratory evaluation should include complete blood count with indices, peripheral smear, iron studies (ferritin, transferrin saturation), and possibly hemoglobin electrophoresis if thalassemia is suspected 1.
  • Patients with severe anemia (hemoglobin <7 g/dL) or symptomatic anemia may require blood transfusion and more urgent evaluation.
  • If oral iron is not tolerated or ineffective, intravenous iron formulations like iron sucrose or ferric carboxymaltose may be necessary 1. The most recent and highest quality study 1 published in 2021 provides guidelines for the management of iron deficiency anemia in adults, which can be applied to the diagnosis and management of anemia with normal LDH levels.

From the Research

Causes of Anemia with Normal Lactate Dehydrogenase (LDH) Levels

  • Iron deficiency anemia without overt bleeding, which can be caused by benign gastrointestinal conditions such as iron malabsorption (atrophic gastritis, celiac disease, chronic inflammation, and bariatric surgery) and chronic blood loss due to gastrointestinal ulcerations 2
  • Autoimmune hemolytic anemia (AIHA), which can present with normal serum LDH values, as seen in 25% of AIHA patients in one study 3
  • Deficiency of essential nutrients such as vitamin B12 and folate, which are necessary for the production of red blood cells, can also cause anemia 4
  • Insufficient intake, poor absorption, or overt or occult blood loss can lead to iron deficiency anemia, a common cause of anemia 5
  • Other rare blood disorders, such as enzymopathies, hemoglobinopathies, and congenital and acquired disorders of red blood cell, can also cause anemia with normal LDH levels 6

Diagnostic Considerations

  • A full blood count is the first-line laboratory test for suspected anemia, and results may suggest a nutritional deficiency of iron, vitamin B12, or folate 4
  • Further testing, such as serological celiac disease screening, bidirectional endoscopy, and small intestine investigation, may be necessary to determine the underlying cause of anemia 2
  • A differential diagnosis of anemia should consider the morphological classification of anemia, including macrocytic, normocytic, and microcytic types, as well as the presence of increased peripheral blood reticulocytes 6

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

[Autoimmune hemolytic anemia with normal serum lactate dehydrogenase level].

[Rinsho ketsueki] The Japanese journal of clinical hematology, 2015

Research

The Evidence-Based Evaluation of Iron Deficiency Anemia.

The Medical clinics of North America, 2016

Research

[Differential diagnosis of anemia].

Vnitrni lekarstvi, 2018

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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