Blood counts for anemia: Understanding hemoglobin, red blood cells, ferritin, and reticulocytes

Anemia is not a single diagnosis, but a laboratory and clinical syndrome in which the blood lacks the ability to transport oxygen to tissues. The primary indicator for the initial detection of anemia is hemoglobin, but it is not the only one that needs to be assessed correctly: red blood cells, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin content, red blood cell size distribution, reticulocytes, blood smear, and iron metabolism parameters are also important. In 2024, the World Health Organization updated its guidelines on hemoglobin thresholds for defining anemia, emphasizing that interpretation depends on age, gender, pregnancy, altitude, and other factors. [1]

A complete blood count (CBC) is a starting point, but it rarely provides a complete answer to the cause of anemia. It shows whether hemoglobin is low and what type of red blood cells are prevalent: small, normal, or large. Using this information, the doctor can narrow down the causes: iron deficiency anemia is more often associated with small and pale red blood cells, vitamin B12 or folate deficiency with large red blood cells, and anemia of chronic disease, chronic kidney disease, or early blood loss often has normal-sized red blood cells. [2]

A very important indicator is reticulocytes, which are young red blood cells recently released from the bone marrow. If reticulocytes are abundant, the bone marrow is actively responding to the loss or destruction of red blood cells; if reticulocytes are low, the body is not producing enough new red blood cells. Therefore, reticulocytes help distinguish anemia due to blood loss or hemolysis from anemia due to iron deficiency, vitamin deficiency, chronic inflammation, kidney disease, or bone marrow damage. [3]

The same hemoglobin level in two people can indicate different clinical situations. For example, a slow decrease in hemoglobin to 100 grams per liter may be relatively tolerable, while a rapid drop to the same level due to bleeding may be accompanied by weakness, palpitations, a drop in blood pressure, and fainting. Therefore, a doctor evaluates not only the hemoglobin level but also the rate of change, symptoms, pulse rate, blood pressure, age, pregnancy, heart disease, kidney disease, and the presence of bleeding. [4]

The most common mistake is trying to treat "low hemoglobin" without understanding the cause. Iron helps with confirmed iron deficiency, vitamin B12 with its deficiency, folic acid with folate deficiency anemia, but hemolysis, chronic kidney disease, myelodysplastic syndrome, leukemia, or bleeding require a completely different approach. Therefore, blood counts should be read as a system, not as individual numbers. [5]

Group of indicators	What does it show?	Why is it important for anemia?
Hemoglobin and hematocrit	How much is the oxygen capacity of the blood reduced?	They confirm the fact of anemia
Erythrocyte indices	Size and saturation of red blood cells with hemoglobin	They help to divide anemia into microcytic, normocytic and macrocytic
Reticulocytes	Bone marrow response	Distinguish between poor production and loss or destruction of red blood cells
Iron levels	Iron reserves and availability	Needed for the diagnosis of iron deficiency and functional iron deficiency
Vitamin B12 and folic acid	Material for normal maturation of blood cells	Helps identify megaloblastic anemia
Hemolysis markers	Destruction of red blood cells	Needed if hemolytic anemia is suspected

Hemoglobin, red blood cells and hematocrit

Hemoglobin is the main indicator used to determine the presence of anemia. It is a protein inside red blood cells that carries oxygen from the lungs to the tissues. According to the World Health Organization, anemia is defined as a hemoglobin concentration below the age-, gender-, and physiological threshold. For non-pregnant women, a threshold of below 120 grams per liter is often used, for men, below 130 grams per liter, and during pregnancy, thresholds vary depending on the stage. [6]

Red blood cells (RBCs ) are the red blood cells that carry hemoglobin. Their numbers can be reduced in anemia, but sometimes the RBC count appears relatively intact, yet the hemoglobin content in each cell is low. This occurs, for example, in iron deficiency anemia and some inherited variants of microcytosis, so the RBC count should be assessed along with the mean corpuscular volume (MCV), mean hemoglobin content (MHC), and blood smear. [7]

Hematocrit indicates the proportion of blood volume occupied by red blood cells. In anemia, it usually decreases because red blood cells or hemoglobin are depleted. However, hematocrit depends on more than just red blood cells: it may appear higher in dehydration and lower in excess fluid, so it cannot be considered separately from hemoglobin, clinical status, and other tests. [8]

The severity of anemia cannot be determined solely by how you feel. Some people adapt to a slow decline in hemoglobin and complain only of fatigue for a long time, while others, even with moderate anemia, experience shortness of breath, palpitations, and dizziness. Hemoglobin levels should be interpreted with particular caution in the elderly, pregnant women, and patients with heart disease, chronic kidney disease, and cancer. [9]

It's important to consider the units of measurement. In different countries, hemoglobin may be reported in grams per liter or grams per deciliter: 120 grams per liter equals 12 grams per deciliter. An error in units can lead to an incorrect assessment of the severity of anemia, so when reading test results, always consider not only the number but also the unit of measurement, the laboratory's reference range, and the doctor's comments. [10]

Indicator	What does it mean?	How does it usually change with anemia?	Practical commentary
Hemoglobin	Oxygen-carrying protein amount	It's decreasing	The main indicator for detecting anemia
Red blood cells	Red blood cell count	Often decreases, but not always proportionally to hemoglobin	It is necessary to look at it together with the red blood cell indices.
Hematocrit	The proportion of blood occupied by red blood cells	Usually decreases	May become distorted with dehydration or excess fluid
Color and shape of red blood cells	Assessed by blood smear	Varies depending on the reason	They help to clarify the type of anemia
Dynamics of indicators	Comparison with previous analyses	May show acute or chronic course	A rapid decline is more dangerous than stable chronic anemia.

Erythrocyte indices: cell size, color, and heterogeneity

The mean corpuscular volume (MCV) measures the average size of red blood cells. If it is low, the anemia is called microcytic; if it is normal, it is normocytic; if it is high, it is macrocytic. This is one of the most useful indicators: microcytosis suggests iron deficiency anemia, thalassemia, and anemia of chronic inflammation, while macrocytosis suggests vitamin B12 deficiency, folate deficiency, liver disease, alcohol, hypothyroidism, certain medications, and myelodysplastic syndromes. [11]

The average corpuscular hemoglobin content (MCHB) indicates the amount of hemoglobin per red blood cell. Iron deficiency often reduces this value because the red blood cells become "poorer" in hemoglobin. This value may be abbreviated on forms, but it essentially answers a simple question: is there enough hemoglobin within each red blood cell? [12]

The mean corpuscular hemoglobin concentration (MCH) measures how tightly hemoglobin is packed within the red cell. This value may be reduced in hypochromic anemias, where the red blood cells appear paler. However, it is rarely diagnostic on its own; it is assessed in conjunction with the mean corpuscular volume (MCV), red blood cell size distribution, ferritin, transferrin saturation, and blood smear. [13]

The red blood cell size distribution ratio (RBCSDR) shows how much the cells vary in size from one another. If the ratio is high, the blood contains many red blood cells of varying sizes; this is often the case with iron deficiency anemia, mixed deficiencies, recovery from treatment, or after blood loss. The Cleveland Clinic notes that this ratio is part of a complete blood count (CBC) and helps the doctor evaluate anemia and related conditions. [14]

It's important to understand the limitations of red blood cell indices: they provide guidance but are not a substitute for diagnosing the underlying cause. For example, a low mean corpuscular volume does not always indicate iron deficiency, as a similar pattern can occur with thalassemia and anemia of chronic inflammation. A high mean corpuscular volume does not always indicate vitamin B12 deficiency, as macrocytosis can occur with alcohol, liver disease, hypothyroidism, and certain medications. [15]

Indicator on the form	Full name	What does it show?	Typical hint
Mean corpuscular volume	Average size of a red cell	Small, normal, or large red blood cells	Low - iron deficiency or thalassemia; high - vitamin B12, folate or other causes
Mean corpuscular hemoglobin content	The amount of hemoglobin in 1 cell	How much is a cell "filled" with hemoglobin?	Decreases with iron deficiency
Mean corpuscular hemoglobin concentration	Intracellular hemoglobin concentration	Degree of hypochromia	Helps confirm the paleness of red blood cells
Distribution of red blood cells by size	Red blood cell volume distribution	Homogeneity or heterogeneity of cells	Often elevated in iron deficiency and mixed deficiencies
Blood smear	The appearance of cells under a microscope	Shape, size, inclusions, pathological cells	It is necessary if automatic indicators do not explain the picture

Reticulocytes: Is bone marrow responsible?

Reticulocytes are young red blood cells that have recently been released from the bone marrow. If the body loses blood or red blood cells are rapidly destroyed, the bone marrow must accelerate the production of new cells, and reticulocytes increase. If anemia is present and reticulocytes are low, this means the bone marrow is not responding actively enough or lacks the resources for adequate hematopoiesis. [16]

Low reticulocytes in anemia often indicate hypoproliferative anemia, which is anemia with insufficient red blood cell production. Causes can include iron deficiency, vitamin B12 deficiency, folate deficiency, chronic inflammation, chronic kidney disease, aplastic anemia, myelodysplastic syndrome, leukemia, medications, or bone marrow damage. Therefore, reticulocytes help quickly determine whether the problem lies in cell production, loss, or destruction. [17]

High reticulocytes in anemia often indicate that the bone marrow is trying to compensate for the loss of red blood cells. This occurs after bleeding, with hemolytic anemia, and during successful treatment of deficiency anemia, when the bone marrow "wakes up" and begins actively releasing new cells. If hemolysis is suspected, reticulocytes are assessed along with bilirubin, lactate dehydrogenase, haptoglobin, and a blood smear. [18]

The reticulocyte percentage can sometimes be misleading. If red blood cells are low, the percentage of young cells may appear elevated, even though the absolute reticulocyte count is insufficient. Therefore, in clinical practice, it is more important to look at the absolute reticulocyte count or the adjusted reticulocyte ratio, which takes into account the severity of anemia. [19]

Reticulocytes are also useful for monitoring treatment. With effective therapy with iron, vitamin B12, or folic acid, the bone marrow usually begins releasing more reticulocytes before hemoglobin rises significantly. If the expected reticulocyte response is not achieved, the physician reviews the diagnosis, dosage, treatment adherence, absorption, ongoing blood loss, inflammation, or underlying bone marrow disease. [20]

Reticulocytes in anemia	What does this usually mean?	Possible reasons
Low	Bone marrow responds weakly	Iron deficiency, vitamin B12, folate, inflammation, kidney disease, aplasia, myelodysplasia
Normal, but anemia is pronounced	The response may not be sufficient for the degree of anemia.	An assessment of the absolute number and the clinical situation is needed.
Tall	Bone marrow compensates for the loss or destruction of red blood cells	Blood loss, hemolysis, recovery after treatment
They grow after treatment.	Bone marrow response has appeared	Usually a good sign if diagnosed correctly
They don't grow after treatment.	We need to look for the reason for the weak response.	Misdiagnosis, poor absorption, ongoing blood loss, inflammation

Iron indices: ferritin, transferrin, and transferrin saturation

Ferritin measures the body's iron stores. In iron deficiency anemia, it is usually low because the body has used up stored iron and the bone marrow lacks the necessary material to synthesize hemoglobin. The British Society of Gastroenterology notes that serum ferritin is the most useful single marker for iron deficiency anemia, but its diagnostic accuracy is reduced by inflammation. [21]

Transferrin saturation measures the proportion of the transport protein transferrin occupied by iron. This indicator is particularly important when ferritin is normal or elevated but there is chronic inflammation, chronic kidney disease, heart failure, liver disease, or cancer. The Kidney Disease: Improving Global Outcomes 2026 guideline emphasizes that ferritin and transferrin saturation have limitations but remain the primary tests for assessing iron status in the anemia of chronic kidney disease. [22]

Serum iron alone is less reliable because it fluctuates throughout the day and is influenced by diet, inflammation, and recent iron supplementation. Therefore, it is rarely used alone; it is more often assessed in conjunction with ferritin, transferrin, or total iron-binding capacity, and transferrin saturation. In iron deficiency, serum iron and transferrin saturation are typically decreased, while transferrin or total iron-binding capacity are often increased. [23]

With chronic inflammatory anemia, the picture is different. Iron may be present in the body, but it is less readily available to the bone marrow because inflammatory mechanisms retain it in depots. Therefore, ferritin may be normal or high, serum iron low, transferrin low or normal, and transferrin saturation decreased. This is one reason why iron supplementation based solely on hemoglobin levels cannot be prescribed without assessing iron metabolism and the cause of the inflammation. [24]

In 2024-2025, clinical literature continues to highlight the problem of choosing a ferritin threshold. A threshold that is too low can miss early iron deficiency, while one that is too high can lead to overdiagnosis, especially in cases of inflammation. Therefore, doctors look not at a "magic number," but at a combination of symptoms, hemoglobin, mean corpuscular volume, red blood cell size distribution, ferritin, transferrin saturation, and potential blood loss. [25]

Indicator	For iron deficiency anemia	In case of anemia of inflammation	Comment
Ferritin	Usually low	Often normal or high	Increased with inflammation and liver disease
Serum iron	Low	Low	In itself it is unstable
Transferrin or iron-binding capacity	Often elevated	Often reduced or normal	Helps to distinguish mechanisms
Transferrin saturation with iron	Low	Low or reduced	Shows the availability of iron
Mean corpuscular volume	Often low with long-term deficiency	Normal or low	It doesn't change right away
Distribution of red blood cells by size	Often elevated	May be normal or elevated	Helps to notice the heterogeneity of cells

Vitamin B12, folate, and macrocytic anemia

Vitamin B12 and folic acid are necessary for normal blood cell maturation. A deficiency disrupts the synthesis of deoxyribonucleic acid in rapidly dividing bone marrow cells, resulting in large red blood cells and ineffective hematopoiesis. This often manifests itself in a complete blood count (CBC) as a high mean corpuscular volume (MCV), and in a smear as large oval red blood cells and hypersegmented neutrophils. [26]

Macrocytosis does not always indicate vitamin B12 or folate deficiency. Large red blood cells can appear in liver disease, alcohol consumption, hypothyroidism, pregnancy, certain medications, myelodysplastic syndromes, and recovery from blood loss or hemolysis. Therefore, a high mean corpuscular volume is not a diagnosis, but a reason to clarify the underlying cause. [27]

Vitamin B12 deficiency is particularly important because it can affect the nervous system. A person may experience numbness, tingling, gait disturbance, burning tongue, memory impairment, weakness, and depressive symptoms. If folic acid is started without checking vitamin B12 levels, the blood test may partially improve, but the neurological impairment will continue to progress. Therefore, it is important to carefully assess both deficiencies in macrocytosis. [28]

Folic acid deficiency anemia can develop with malnutrition, malabsorption, pregnancy, increased folate requirements, chronic alcohol consumption, and certain medications. Blood tests can mimic vitamin B12 deficiency, so the mean corpuscular volume alone cannot differentiate these conditions. Laboratory tests and clinical context assessment are necessary. [29]

If macrocytic anemia is accompanied by low white blood cell or platelet counts, the doctor takes a broader view: it could be a severe vitamin B12 deficiency, myelodysplastic syndrome, bone marrow disease, drug toxicity, or another systemic condition. In such situations, a blood smear, reticulocyte count, biochemical tests, and, if necessary, a consultation with a hematologist are especially important. [30]

Situation	Possible blood indicators	What needs to be clarified
Vitamin B12 deficiency	High mean corpuscular volume, low hemoglobin, sometimes low white blood cells and platelets	Vitamin B12, neurological symptoms, cause of deficiency
Folic acid deficiency	Macrocytic anemia resembling vitamin B12 deficiency	Folic acid, nutrition, pregnancy, medications
Alcohol or liver disease	Macrocytosis with or without anemia	Liver function tests, medical history, nutrition
Hypothyroidism	Macrocytosis or normocytic anemia	Thyroid hormones
Myelodysplastic syndrome	Macrocytosis, cytopenia, dysplasia in smear	Hematologist, bone marrow as indicated

Markers of hemolysis and blood loss

Hemolysis is the premature destruction of red blood cells. In hemolytic anemia, the bone marrow typically attempts to compensate for the loss, so reticulocytes increase if they have sufficient resources. A physician suspects hemolysis when anemia is accompanied by a high reticulocyte count, elevated indirect bilirubin, elevated lactate dehydrogenase, decreased haptoglobin, and changes in the blood smear. [31]

Haptoglobin is a protein that binds free hemoglobin, which is produced by the destruction of red blood cells. During hemolysis, haptoglobin levels often decrease because it is used up to bind free hemoglobin. However, this indicator is not perfect: it can change with inflammation, liver disease, and other conditions, so it is evaluated in conjunction with other markers. [32]

The direct antiglobulin test, often called the direct Coombs test, is used when autoimmune hemolytic anemia is suspected. It helps detect antibodies or complement components on the surface of red blood cells. Professional references emphasize that autoimmune hemolytic anemia should be suspected when signs of hemolysis are present, and confirmation of the cause requires specific tests. [33]

Blood loss can be overt or hidden. Overt blood loss includes heavy menstrual bleeding, nosebleeds, blood in the stool, hematemesis, trauma, or surgery. Occult blood loss is more often associated with the gastrointestinal tract and may long present only with iron deficiency anemia, weakness, and decreased ferritin. The British Society of Gastroenterology emphasizes the importance of identifying the cause of iron deficiency anemia in adults, especially in men and postmenopausal women. [34]

After acute blood loss, blood test results may not change immediately. In the first few hours, hemoglobin levels sometimes don't reflect the full extent of blood loss, as the plasma-to-erythrocyte ratio changes gradually. Therefore, if bleeding is suspected, the doctor evaluates not only hemoglobin levels, but also blood pressure, pulse, symptoms, the source of blood loss, blood test progress, and the need for urgent care. [35]

Indicator	In case of hemolysis	In case of blood loss	Practical meaning
Reticulocytes	Usually they increase	Increases after a few days if the bone marrow responds	They show the bone marrow reaction
Bilirubin	Indirect bilirubin may increase.	Usually not the main marker	Helps to suspect the destruction of red blood cells
Lactate dehydrogenase	Often increases	It might be normal	Marker of cellular destruction, non-specific
Haptoglobin	Often decreases	Usually does not decrease in isolation	Supports the diagnosis of hemolysis
Ferritin	It may be different	Decreases in chronic blood loss	Helps identify iron deficiency
Blood smear	May show spherocytes, schistocytes and other changes	May be non-specific	Helps to clarify the mechanism

How are the main types of anemia distinguished using tests?

Iron deficiency anemia typically develops gradually. Initially, ferritin decreases, then iron availability for hematopoiesis decreases, followed by decreased hemoglobin, microcytosis, hypochromia, and an increased red blood cell size distribution. Professional guidelines emphasize that reticulocytes are typically low in iron deficiency, and a smear reveals pale red blood cells with marked heterogeneity in shape and size. [36]

Anemia of chronic inflammation is most often normocytic or moderately microcytic. Ferritin may be normal or elevated because it rises with inflammation, and transferrin saturation is reduced because iron is poorly available to the bone marrow. This pattern is seen in chronic infections, autoimmune diseases, chronic kidney disease, cancer, and other long-term inflammatory conditions. [37]

Megaloblastic anemia due to vitamin B12 or folate deficiency is typically accompanied by macrocytosis, a low reticulocyte count, and characteristic changes on the blood smear. In severe deficiency, not only red blood cells but also white blood cells and platelets may be reduced, sometimes suggesting bone marrow disease. Therefore, it is important to check vitamin B12 and folate levels before making more invasive diagnoses. [38]

Hemolytic anemia is characterized by red blood cell destruction at a faster rate than usual. It is characterized by reticulocytosis, elevated bilirubin, elevated lactate dehydrogenase, low haptoglobin, and specific changes in the smear. If the hemolysis is autoimmune, a direct antiglobulin test is important; if schistocytes are present, the physician considers mechanical destruction of red blood cells and microangiopathic processes. [39]

Anemia due to bone marrow damage is often accompanied by additional abnormalities: low white blood cell count, low platelet count, blasts, dysplastic cells, or persistent unexplained macrocytic anemia. In myelodysplastic syndromes, cytopenias are a characteristic feature, and blood cells may be poorly formed and function poorly. In such cases, consultation with a hematologist and often bone marrow examination are necessary. [40]

Type of anemia	Mean corpuscular volume	Reticulocytes	Ferritin and iron	Additional tips
Iron deficiency	Often low	Often low	Ferritin is low, transferrin saturation is low	High red blood cell size distribution, pale red blood cells
Anemia of inflammation	Normal or low	Low or normal	Ferritin is normal or high, transferrin saturation is decreased	There is chronic inflammation or disease
Vitamin B12 deficiency	High	Often low	Iron is not the main marker	Neurological symptoms, large red blood cells
Folic acid deficiency	High	Often low	Iron is not the main marker	Nutrition, pregnancy, medications, alcohol
Hemolytic	Varies, sometimes elevated due to reticulocytes	Increased	Iron may be normal or elevated.	Bilirubin and lactate dehydrogenase are elevated, haptoglobin is decreased
Bone marrow cause	Often normal or high	Often low	Diverse	Low white blood cells, low platelets, blasts, dysplasia

When blood counts require urgent evaluation

Urgent evaluation is necessary if low hemoglobin is accompanied by shortness of breath at rest, chest pain, syncope, confusion, severe weakness, a very rapid pulse, a drop in blood pressure, black stools, vomiting of blood, or active bleeding. These signs may indicate severe anemia, acute blood loss, a cardiac complication, or another emergency. International guidelines for red blood cell transfusion emphasize that the decision to transfuse depends not only on the hemoglobin level but also on symptoms, circulatory stability, and the clinical context. [41]

A combination of anemia and low platelets or white blood cells is especially concerning. If several cell lines are reduced, the problem may lie not only in the iron, but also in the bone marrow, medication exposure, infection, autoimmune disease, myelodysplastic syndrome, or leukemia. A particularly urgent response is required if a blood test shows blasts or a fever associated with low neutrophils. [42]

In men and postmenopausal women, iron deficiency anemia requires investigation of the source of blood loss, particularly from the gastrointestinal tract. Iron supplementation alone should not be used if the cause of the deficiency is unclear. British gastroenterology guidelines emphasize the need for evaluation of adults with iron deficiency anemia to identify the underlying cause, including possible occult blood loss. [43]

Pregnant women, children, the elderly, and patients with heart disease or chronic kidney disease have lower alarm thresholds. Even moderate anemia may be less tolerable because oxygen requirements are higher or cardiovascular reserve is lower. Therefore, in these groups, it is important not to wait for severe symptoms and to discuss test results with a doctor promptly. [44]

If anemia is already being treated, but hemoglobin levels are not increasing, this is also a reason to reconsider the diagnosis. Possible causes include ongoing blood loss, poor absorption, incorrect medication administration, inflammation, mixed deficiency, kidney disease, hemolysis, or bone marrow disease. A good diagnosis doesn't end with prescribing treatment: it also checks whether the body is responding as expected. [45]

Situation	Why is it alarming?	What is usually required
Low hemoglobin and chest pain	The heart may not have enough oxygen.	Urgent medical assessment
Anemia and black stool	Possible gastrointestinal bleeding	Urgent examination
Anemia plus low platelets	Risk of bleeding and bone marrow disease	Consultation with a doctor, sometimes a hematologist
Anemia plus low neutrophils and fever	Risk of severe infection	Urgent help
Blasts in the blood	Possible acute leukemia	Urgent hematological diagnostics
No response to treatment	Possibly incorrect or incomplete reason	Review of diagnosis and scheme

Frequently asked questions

Can anemia be diagnosed based solely on hemoglobin? Hemoglobin is typically used to determine the presence of anemia, but it cannot determine the cause. To determine the cause, red blood cell indices, reticulocytes, a blood smear, ferritin, transferrin saturation, vitamin B12, folate, and other tests are needed. [46]

What is the most important indicator for anemia? Hemoglobin is the most important indicator for detecting anemia, but mean corpuscular volume and reticulocytes are especially important for understanding the mechanism. The former helps determine the type of anemia based on red blood cell size, while the latter shows how actively the bone marrow is responding to the problem. [47]

Why might ferritin be normal with iron deficiency? Ferritin increases with inflammation, infections, chronic kidney disease, liver disease, heart failure, and some tumors. Therefore, in cases of inflammation, the physician additionally evaluates transferrin saturation and the overall clinical picture. [48]

What does low mean corpuscular volume mean? Low mean corpuscular volume means that the red blood cells are smaller than normal. This is most often seen in iron deficiency anemia, but can also occur in thalassemia and anemia of chronic inflammation, so an iron analysis and assessment of the family, ethnic, and clinical context are necessary. [49]

What does a high mean corpuscular volume mean? A high mean corpuscular volume means macrocytosis, meaning large red blood cells. Causes include vitamin B12 deficiency, folate deficiency, alcohol, liver disease, hypothyroidism, certain medications, recovery from blood loss, or bone marrow disease. [50]

Why are reticulocytes important? Reticulocytes indicate whether the bone marrow is producing new red blood cells in response to anemia. High reticulocytes often indicate blood loss or hemolysis, while low reticulocytes indicate poor production due to deficiency, inflammation, kidney disease, or bone marrow failure. [51]

When should vitamin B12 be tested? Vitamin B12 should be tested in cases of macrocytic anemia, numbness, tingling, burning of the tongue, gait disturbance, memory loss, long-term use of certain medications, a vegan diet, stomach or intestinal diseases, and after stomach surgery. It is important not to treat such situations with folic acid alone without assessing vitamin B12. [52]

When is a bone marrow biopsy needed? A bone marrow biopsy is not needed for every anemia, but for unexplained anemia, pancytopenia, blasts in the blood, suspected aplastic anemia, myelodysplastic syndrome, leukemia, lymphoma, myeloma, or other bone marrow disorders. The decision is usually made by a hematologist after a basic blood test. [53]

Key points from experts

Thomas J. DeLaffery, MD, professor of medicine at Oregon Health & Science University and author of the 2024 American Gastroenterological Association clinical update on iron deficiency anemia, emphasizes that treatment for iron deficiency must be tolerable and the cause of the deficiency must be identified. The practical takeaway: low hemoglobin and low ferritin should not be viewed simply as a "take iron supplement" response, especially in adults with potential blood loss. [54]

Jeffrey L. Carson, MD, lead author of the 2023 AABB International Guidelines for Red Blood Cell Transfusion, emphasizes a clinically informed approach to transfusion. The bottom line: The decision to transfuse depends on hemoglobin, symptoms, bleeding, circulatory stability, and comorbidities, not just the desire to quickly “get a number up.” [55]

Jody L. Babbitt, MD, and Marcello Tonelli, MD, co-authors of the executive summary of the Kidney Disease: Improving Global Outcomes 2026 guidelines on anemia in chronic kidney disease, emphasize the limitations of ferritin and transferrin saturation but retain them as key tests for assessing iron. The practical takeaway: In chronic kidney disease, blood counts should be read taking into account inflammation, iron availability, erythropoietin signaling, and cardiovascular risk. [56]

Robert T. Means, Jr., MD, a renowned expert on the anemia of inflammation, emphasized that inflammation alters the availability of iron for hematopoiesis. The practical implication is that normal or high ferritin does not always mean that the bone marrow is receiving sufficient iron, so transferrin saturation and the overall inflammatory context are important in chronic diseases. [57]

Peter L. Greenberg, MD, a specialist in myelodysplastic syndromes, emphasized the importance of persistent cytopenias, cell morphology, and bone marrow examination when suspecting hematopoietic disorders. The practical lesson: if anemia is associated with low white blood cells, low platelets, blasts, or persistent macrocytosis, iron and vitamin supplements should not be used without a hematologic evaluation. [58]

Conclusion

Blood tests for anemia should be evaluated sequentially: first, confirm a decrease in hemoglobin, then determine the size and saturation of red blood cells, evaluate the bone marrow reticulocyte response, check iron, vitamin B12, folate, and, if necessary, hemolysis markers, kidney function, inflammation, and a blood smear. This approach allows us not only to name the anemia, but also to understand its mechanism. [59]

The main mistakes in interpreting blood tests are relying solely on hemoglobin, assuming any anemia is due to iron deficiency, ignoring reticulocytes, failing to consider inflammation when interpreting ferritin, and failing to recognize the combination of anemia with low white blood cells or platelets. These are the errors that most often delay proper diagnosis. [60]

Correct interpretation of test results always takes into account the individual, not just the form: age, pregnancy, symptoms, rate of hemoglobin decline, blood loss, medications, diet, chronic illnesses, kidney function, and family history of blood disorders. If blood results don't fit the typical pattern or treatment doesn't produce the expected response, don't proceed blindly; review the diagnosis with your doctor. [61]