Lab result explainedBlood count (CBC)Last updated November 11, 2026

Anisocytosis: what 1+, mild and moderate red cell size variation means

Anisocytosis · Peripheral blood smear (reported with the complete blood count) · reported in Semiquantitative grade on the smear (slight/1+ to marked/3+ or 4+); RDW-CV in percent or RDW-SD in femtoliters (fL)

Anisocytosis means that your red blood cells vary more than usual in size. It is a description from a peripheral blood smear, where a laboratory scientist looks at a stained drop of your blood under the microscope, and it is usually graded as slight or 1+, moderate or 2+, and marked or 3+ (some labs use a 4+ grade). The same information appears as a number on the automated complete blood count: the red cell distribution width (RDW), which is normal at about 11.5 to 14.5 percent. Anisocytosis on the smear and a high RDW are two ways of reporting the same thing.

Healthy red cells are remarkably uniform, about 7 to 8 micrometers across, because the bone marrow releases them at a consistent size and they live about 120 days. Size variation appears when the marrow starts producing cells that are too small (iron deficiency, thalassemia), too large (vitamin B12 or folate deficiency, liver disease, heavy alcohol use), when old and new populations mix (after a transfusion or in the first weeks of treating a deficiency), or when cells are being damaged in the circulation. Iron deficiency is by far the most common cause of anisocytosis in adults.

A report of 1+ or mild anisocytosis with a normal hemoglobin, a normal MCV and an RDW only just above range is common and often means nothing on its own. It becomes informative when the hemoglobin is low or the MCV is abnormal, because the pattern of size variation then helps sort out why. This page explains how anisocytosis is graded, what the common causes are, how it differs from poikilocytosis (abnormal shape rather than size) and which tests usually come next.

Anisocytosis at a glance

What it is: more variation in red blood cell size than normal, seen on a blood smear; the automated equivalent is a raised RDW.
Grading: slight/1+, moderate/2+, marked/3+ (some labs add 4+). Normal RDW-CV is about 11.5–14.5%; normal RDW-SD about 39–46 fL. Labs differ.
Most common causes: iron deficiency, vitamin B12 or folate deficiency, thalassemia, recent transfusion, the first weeks of treating any anemia, liver disease and heavy alcohol use.
Mild (1+) anisocytosis with a normal hemoglobin and MCV is a frequent, usually unimportant finding; moderate or marked anisocytosis with anemia needs a cause.
Anisocytosis is about size; poikilocytosis is about shape. The two often appear together on the same report.
Next step: read it with hemoglobin, MCV, MCH and RDW, then ferritin, B12, folate and a reticulocyte count as the pattern suggests.

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What Anisocytosis measures

A peripheral blood smear is a thin film of blood spread on a glass slide, dried, stained (usually Wright or Wright-Giemsa) and examined at high magnification. In the area where cells lie in a single layer, the scientist compares red cells with each other and with the nucleus of a small lymphocyte, which is about the same diameter as a normal red cell. If the cells are mostly the same size, the smear is reported as normal; if an unusual proportion are smaller (microcytes) or larger (macrocytes) than the rest, the degree of spread is reported as anisocytosis and graded. The grade is a trained estimate rather than an exact count, so a 1+ at one laboratory may be reported as slight or mild at another.

The automated counterpart is the RDW, calculated by the hematology analyzer from the size of tens of thousands of individual red cells. RDW-CV is the standard deviation of cell volume divided by the mean cell volume, expressed as a percentage; RDW-SD is the width of the size distribution curve in femtoliters measured at 20 percent of its height. Because RDW-CV is divided by the MCV, it is exaggerated when cells are small and understated when they are large, which is why some labs report both. International guidance (ICSH) suggests laboratories grade anisocytosis primarily from the RDW rather than from the microscope, so on many reports the smear comment simply mirrors the number.

Anisocytosis is a pattern, not a diagnosis. Its value lies in combination: small and variable cells point to iron deficiency; small cells that are uniform point to thalassemia trait; large and variable cells point to B12 or folate deficiency; two distinct populations (a dimorphic picture) point to a recent transfusion, a mixed deficiency or sideroblastic anemia. Artifacts matter too: a smear made from blood that has sat in the tube for many hours, or spread too thickly, can look more variable than it is, and a few analyzers flag anisocytosis when the real problem is clumped platelets or fragments.

Normal range for Anisocytosis

Reference ranges vary between labs and by age, sex and pregnancy. Use the range printed on your own report.

Group	Typical range (Semiquantitative grade on the smear (slight/1+ to marked/3+ or 4+); RDW-CV in percent or RDW-SD in femtoliters (fL))	Notes
Normal smear	No anisocytosis, or 'occasional' microcytes or macrocytes	Red cells about 7–8 µm, close to the diameter of a small lymphocyte nucleus.
Slight or 1+	A noticeable minority of cells outside the usual size range	Common with mild iron deficiency, early treatment of anemia, or no disease at all. Usually corresponds to an RDW just above the upper limit.
Moderate or 2+	A substantial fraction of cells smaller or larger than normal	Typical of established iron deficiency, B12 or folate deficiency, or a mixed picture. Nearly always accompanied by an abnormal MCV or hemoglobin.
Marked or 3+ (4+)	Most cells vary widely in size	Severe or combined deficiencies, myelodysplastic syndrome, thalassemia major, severe hemolysis, or after transfusion.
RDW-CV, normal adults	About 11.5–14.5%	Some labs use 11.0–15.0%. A value above range is the numerical form of anisocytosis.
RDW-SD, normal adults	About 39–46 fL	Less affected by the MCV than RDW-CV; preferred by some labs when cells are small or large.
Newborns and infants	RDW up to about 15–18% is usual in the first months	A mix of fetal and adult-type cells is normal; the RDW settles to adult values during the first year.
Dimorphic population	Two separate peaks on the size histogram	Recent transfusion, iron deficiency treated with iron in the last few weeks, combined iron and B12 or folate deficiency, or sideroblastic anemia.

Anisocytosis present (1+ to 3+)

Anisocytosis tells you that the red cells in your blood were not all made under the same conditions. Because red cells live about four months, a smear is a snapshot of cells produced across that whole period, and any change in the raw materials the marrow had available, or any process that removes or damages cells selectively, shows up as a wider spread of sizes. In adults, the single most common explanation is iron deficiency, in which the RDW often rises before the hemoglobin or MCV leaves the normal range, making anisocytosis one of the earliest clues.

The grade matters less than the company it keeps. Slight or 1+ anisocytosis with a normal hemoglobin, a normal MCV and an RDW of 14 to 15 percent is reported in many healthy people and in most people recovering from a minor illness; on its own it rarely needs more than a repeat count in a few months, or a ferritin if there is any reason to suspect low iron (heavy periods, a plant-based diet, pregnancy, a history of stomach or bowel disease). Moderate or marked anisocytosis almost always comes with anemia or an abnormal MCV, and the combination points firmly at a cause: low MCV with high RDW is iron deficiency until proven otherwise; high MCV with high RDW is B12 or folate deficiency, liver disease, alcohol or a marrow disorder; normal MCV with high RDW is often early or mixed deficiency, hemolysis or recent bleeding with a brisk reticulocyte response.

Anisocytosis also appears during recovery, and here it is a good sign rather than a bad one. In the first two to eight weeks after starting iron, B12 or folate, the marrow releases a wave of new, normally sized or slightly large cells (reticulocytes) into a population of old small or large ones, so the RDW climbs and the smear becomes markedly dimorphic before everything settles back to normal over two to four months. A rising RDW shortly after treatment starts is therefore expected; a persistently high RDW three to four months later means the deficiency has not been corrected or something else is going on.

Common causes

Iron deficiency
The marrow makes progressively smaller, paler cells as iron runs short while older normal cells are still in circulation, so size variation rises early. Typical pattern: RDW above 15%, MCV falling toward or below 80 fL, low MCH, low ferritin. Causes include heavy menstrual bleeding, gastrointestinal blood loss, pregnancy, celiac disease and low dietary iron.
Vitamin B12 or folate deficiency
Impaired DNA synthesis produces large oval cells (macro-ovalocytes) with a high RDW and an MCV often above 100 fL, usually with hypersegmented neutrophils on the same smear. Pernicious anemia, metformin, acid-suppressing drugs, gastric surgery, alcohol and a vegan diet without supplementation are the usual reasons.
Early treatment of any nutritional anemia
Within one to two weeks of starting iron, B12 or folate, a surge of new cells of normal size mixes with the old abnormal ones, producing a dimorphic smear and a temporary further rise in RDW. This is the expected course and resolves over two to four months.
Recent blood transfusion
Donor cells of normal size circulate alongside your own smaller or larger cells, so a transfusion within the previous three months produces two distinct size populations and marked anisocytosis that is not itself a disease.
Thalassemia and other hemoglobinopathies
Beta thalassemia trait usually gives uniformly small cells with a normal or only mildly raised RDW, which is one of the ways it is distinguished from iron deficiency, but thalassemia intermedia and major, hemoglobin H disease and sickle cell disease produce marked anisocytosis with target cells and fragments.
Liver disease and heavy alcohol use
Alcohol is directly toxic to developing red cells and chronic liver disease alters the cell membrane, producing round macrocytes, target cells and a raised RDW even without anemia. The MCV typically sits between 100 and 110 fL and falls over two to four months of abstinence.
Hemolysis and bleeding with a reticulocyte response
Reticulocytes are about 20 percent larger than mature red cells, so any brisk marrow response to blood loss or destruction widens the size spread. In hemolysis, small dense spherocytes or fragments add further variation. Look for a high reticulocyte count, raised LDH and bilirubin and a low haptoglobin.
Myelodysplastic syndrome and other marrow disorders
Abnormal clones of marrow cells release red cells of inconsistent size, often with macrocytosis, a markedly raised RDW, oval cells and low counts in other cell lines. More likely over age 60 and when anemia is unexplained by iron, B12, folate, kidney or thyroid testing.
Chronic kidney disease, hypothyroidism and chronic inflammation
Each blunts red cell production and can combine with iron deficiency to give a mixed population. Anemia of chronic disease alone usually produces normal-sized cells with a normal or mildly raised RDW; a high RDW suggests iron deficiency is also present.
Chemotherapy, some medicines and sideroblastic anemia
Hydroxyurea, methotrexate, azathioprine, zidovudine and some anticonvulsants enlarge red cells; lead exposure, copper deficiency, excess zinc and inherited sideroblastic anemias produce small cells alongside normal ones, giving a classic dimorphic picture.

Symptoms that can go with it

Often none; anisocytosis itself causes no symptoms and is frequently found on a routine blood count
Tiredness, reduced exercise tolerance and breathlessness on exertion if anemia is present
Pale skin, nail beds or inner eyelids, and brittle or spoon-shaped nails with iron deficiency
Restless legs, cravings for ice or non-food substances (pica) and hair shedding with low iron
Numbness or tingling in the hands and feet, unsteadiness, a sore smooth tongue or memory changes with B12 deficiency
Yellowing of the eyes or skin and dark urine if red cells are being destroyed
Easy bruising, frequent infections or unexplained weight loss, which raise the possibility of a marrow disorder and need prompt assessment

Read it alongside

RDW — the numerical version of anisocytosis; an RDW above about 15% with a low MCV points to iron deficiency, with a high MCV to B12, folate, liver or marrow causes.
MCV — tells you which direction the size variation runs: small cells (under 80 fL), large cells (over 100 fL) or a mix around a normal average.
MCH and MCHC — low values confirm the small cells are also pale (iron deficiency, thalassemia); a high MCHC with anisocytosis suggests spherocytes.
Hemoglobin and hematocrit — decide whether the finding matters: anisocytosis without anemia is a watch-and-recheck finding, with anemia it needs a cause.
Ferritin, iron saturation and TIBC — a ferritin under 30 ng/mL confirms iron deficiency as the reason for microcytic anisocytosis; under 15 is diagnostic.
Vitamin B12 and folate — ordered when the MCV is high or the smear shows macro-ovalocytes and hypersegmented neutrophils.
Reticulocyte count — high after bleeding, hemolysis or recent treatment (explaining the size spread); low when the marrow itself is the problem.
Poikilocytosis and other smear comments — target cells, pencil cells, teardrops, fragments or spherocytes narrow the cause considerably.

What usually happens next

If you are not anemic and the MCV is normal, 1+ anisocytosis usually needs nothing beyond a repeat CBC in three to six months, unless you have a reason to be low in iron, in which case a ferritin is reasonable now.
If the MCV is low or borderline, expect ferritin, iron saturation and TIBC; if ferritin is normal and the red cell count is high, the next test is hemoglobin electrophoresis for thalassemia trait.
If the MCV is high, expect vitamin B12, folate, liver enzymes, thyroid function and a reticulocyte count, and an honest conversation about alcohol intake and medicines.
If you have recently started iron, B12 or folate, or had a transfusion, the anisocytosis is expected; the useful recheck is a CBC and ferritin three months after treatment began.
Anisocytosis with anemia that remains unexplained after these tests, particularly over age 60 or with low white cells or platelets, is referred to hematology, where a repeat smear review and sometimes a bone marrow examination follow.

Diet, lifestyle and natural levers with evidence

What can move Anisocytosis once the cause is known. Nothing here replaces finding the cause.

Correct iron deficiency: diet plus supplementation when ferritin is low

Strong evidence

Anisocytosis from iron deficiency resolves only when iron stores are rebuilt. Oral iron raises hemoglobin by about 1 g/dL every two to three weeks, the RDW rises further for the first few weeks as new cells appear and then normalizes over two to four months, and ferritin takes three to six months to replete. Heme iron from red meat, poultry and fish is absorbed at 15 to 35 percent, versus 2 to 20 percent for plant iron; pairing plant sources with vitamin C-rich foods roughly doubles absorption from that meal, although a 2020 randomized trial found adding vitamin C tablets to iron supplements made no measurable difference to the hemoglobin response.

Do not take iron for anisocytosis without a low ferritin; in thalassemia trait or hemochromatosis, extra iron accumulates. Iron supplements commonly cause constipation, nausea and dark stools.

Alternate-day iron dosing

Moderate evidence

Trials using stable iron isotopes in iron-deficient women found that a single morning dose taken every other day was absorbed about a third better per dose than the same dose taken daily, because each dose raises hepcidin for roughly 24 hours and blocks absorption of the next. Taking 60 to 100 mg of elemental iron on alternate days, away from tea, coffee, calcium and antacids, delivers as much iron with fewer gastrointestinal side effects.

Vitamin B12 repletion

Strong evidence

Macrocytic anisocytosis from B12 deficiency responds within days: reticulocytes rise by day five to seven and the MCV and RDW return to normal within about eight weeks. Randomized trials and a Cochrane review found high-dose oral B12 (1,000 to 2,000 µg daily) raised blood levels and corrected anemia as effectively as injections, including in pernicious anemia, because about 1 percent is absorbed passively without intrinsic factor. Older adults, people on metformin or long-term acid suppression, and anyone on a vegan diet are the groups most often deficient.

Neurological symptoms need prompt treatment under medical supervision; folate alone can correct the anemia while nerve damage from untreated B12 deficiency progresses.

Folate from food or a supplement

Strong evidence

Folate deficiency produces the same macrocytic, high-RDW picture as B12 deficiency and corrects just as quickly with 400 µg to 1 mg of folic acid a day or a diet rich in leafy greens, legumes and fortified grains. Since US grain fortification in 1998, dietary folate deficiency is uncommon, so a low folate usually points to alcohol excess, malabsorption, pregnancy, hemolysis or medicines such as methotrexate, phenytoin or trimethoprim.

Check B12 before taking folic acid for macrocytosis.

Reduce or stop alcohol

Moderate evidence

Alcohol is the commonest cause of a high MCV with anisocytosis in people who are not anemic. Observational studies show macrocytosis in a substantial share of people drinking more than about four drinks a day, and the MCV and RDW fall back toward normal over two to four months of abstinence as the affected cells are replaced. The effect is dose-related and independent of folate status.

When to see a clinician promptly

Anisocytosis with a hemoglobin under 8 g/dL, or any anemia with chest pain, breathlessness at rest, fainting or a racing heart: this needs same-day assessment.
Anisocytosis with black, tarry stools, vomiting blood or visibly heavy or prolonged bleeding.
New numbness, tingling, unsteadiness or confusion together with large red cells: possible B12 deficiency affecting the nerves, which should be treated promptly.
Marked (3+) anisocytosis, or anisocytosis with low white cells or platelets, unexplained bruising, fevers or night sweats, which raise the possibility of a marrow disorder.
Jaundice or dark urine with anisocytosis, suggesting red cells are being destroyed.
Anisocytosis that persists or worsens on a repeat count three months after starting treatment for iron, B12 or folate deficiency.

Frequently asked questions

What does anisocytosis 1+ mean?

It means the person examining your blood smear saw slightly more variation in red cell size than normal, the lowest grade on a scale that runs 1+ to 3+ or 4+. On its own, especially with a normal hemoglobin and a normal MCV, it is a common and usually unimportant finding; it is often the microscope's version of an RDW a fraction above the upper limit. It becomes worth pursuing if you are anemic, if the MCV is low or high, or if you have a reason to be short of iron, B12 or folate.

Is mild anisocytosis serious?

Usually not. Mild anisocytosis is seen in healthy people, in anyone recovering from an illness, in pregnancy and in the early weeks of treating anemia. It is a clue rather than a condition. The questions that decide whether it matters are whether your hemoglobin is normal, what your MCV and RDW show, and whether you have symptoms such as fatigue, breathlessness or pallor. If all of those are reassuring, a repeat count in a few months is the usual plan.

What causes anisocytosis?

Iron deficiency is the most common cause and often raises the RDW before the hemoglobin falls. Others are vitamin B12 or folate deficiency, thalassemia and other hemoglobin disorders, liver disease, heavy alcohol use, recent transfusion, the first weeks of treating any anemia, hemolysis, chronic kidney disease, hypothyroidism, some medicines (hydroxyurea, methotrexate, zidovudine) and, less commonly, myelodysplastic syndrome. The MCV tells you which group to look in.

What is the difference between anisocytosis and poikilocytosis?

Anisocytosis is variation in size; poikilocytosis is variation in shape. Both are graded 1+ to 3+ on the smear. They frequently occur together because the same disorders that disturb red cell size also disturb shape, but shape abnormalities are often more specific: pencil cells point to iron deficiency, target cells to liver disease or thalassemia, teardrops to a marrow problem, fragments to mechanical destruction and spherocytes to immune hemolysis or hereditary spherocytosis.

Can anisocytosis occur with a normal hemoglobin?

Yes, and it often does. In early iron deficiency, the RDW is frequently the first index to move, weeks or months before the hemoglobin drops. It is also seen without anemia in people who drink heavily, who take certain medicines, who have mild liver disease, who are recovering from an illness or who have recently been treated for anemia. A normal hemoglobin makes the finding less urgent but not necessarily meaningless; a ferritin is a sensible first check.

What RDW counts as anisocytosis?

Most labs define the normal RDW-CV as roughly 11.5 to 14.5 percent (some allow up to 15), and an RDW-SD of about 39 to 46 fL. Values above these are reported as anisocytosis, with higher grades for higher values. Because RDW-CV is divided by the MCV, people with small cells can have a mildly raised RDW-CV while the RDW-SD is normal; the two together give a fuller picture.

Does anisocytosis go away?

It goes away when the cause is corrected, but not quickly, because red cells live about 120 days and the abnormal population has to be replaced. After starting iron, B12 or folate, expect the RDW to rise for a few weeks (new normal cells mixing with old abnormal ones) and then fall into the normal range over two to four months. Anisocytosis from thalassemia trait or an inherited red cell disorder is lifelong and harmless in itself.

Is anisocytosis a sign of cancer?

Rarely. The overwhelming majority of anisocytosis is nutritional, inherited or related to alcohol, liver or kidney disease. Myelodysplastic syndrome, a bone marrow disorder that can progress to leukemia, does produce marked anisocytosis, but it usually comes with macrocytosis, anemia that no deficiency explains, and often low white cells or platelets, mostly in people over 60. A high RDW has also been linked in population studies to higher overall mortality and heart disease risk, but as a marker of underlying illness rather than a cause.

References

Blood smear. MedlinePlus, US National Library of Medicine (2023)View source
Red blood cell distribution width (RDW). MedlinePlus, US National Library of Medicine (2023)View source
Evaluation of anemia. Merck Manual Professional Version (2024)
Palmer L, Briggs C, McFadden S, et al.. ICSH recommendations for the standardization of nomenclature and grading of peripheral blood cell morphological features. International Journal of Laboratory Hematology (2015)
Bain BJ. Diagnosis from the blood smear. New England Journal of Medicine (2005)
Bessman JD, Gilmer PR Jr, Gardner FH. Improved classification of anemias by MCV and RDW. American Journal of Clinical Pathology (1983)
Salvagno GL, Sanchis-Gomar F, Picanza A, Lippi G. Red blood cell distribution width: a simple parameter with multiple clinical applications. Critical Reviews in Clinical Laboratory Sciences (2015)
Camaschella C. Iron-deficiency anemia. New England Journal of Medicine (2015)
Stoffel NU, Cercamondi CI, Brittenham G, et al.. Iron absorption from oral iron supplements given on consecutive versus alternate days and as single morning doses versus twice-daily split dosing in iron-depleted women: two open-label, randomised controlled trials. Lancet Haematology (2017)
Li N, Zhao G, Wu W, et al.. The efficacy and safety of vitamin C for iron supplementation in adult patients with iron deficiency anemia: a randomized clinical trial. JAMA Network Open (2020)
Wang H, Li L, Qin LL, Song Y, Vidal-Alaball J, Liu TH. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cochrane Database of Systematic Reviews (2018)
Ford J. Red blood cell morphology. International Journal of Laboratory Hematology (2013)

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This page is educational and is not medical advice or a diagnosis. Lab results have to be interpreted together with your history, symptoms and other results by a clinician who knows you. Do not start or stop a supplement to change a lab value before the cause is known.