RDW: Diagnostic Significance and Clinical Insights
Authors: Payal Bhandari M.D.
Contributors: Nigella Umali Ruguain, Vivi Chador, Hailey Chin
Key Insights
The Complete Blood Count (CBC) is a test that measures red blood cells (RBCs), white blood cells (WBCs), and platelets (PLTs). RBCs carry oxygen, WBCs fight infections, and PLTs help with clotting. The CBC also checks the size and volume of RBCs. The Red Blood Cell Distribution Width (RDW) test shows how much RBC sizes vary. A low RDW means RBCs are similar in size, often linked to inflammation. A high RDW means RBCs vary in size, which could signal other problems.
RBCs make up about 45% of blood in adults and 60% in newborns. RBCs contain hemoglobin (Hb), which gives blood its red color. When blood is processed, it separates into three layers: plasma (55% of blood), which is mostly water, and the buffy coat (1%), which contains WBCs and platelets.
Figure 1: Blood is divided into three parts: 55 percent is plasma, which comprises water (93 percent), salts, proteins, lipids, and glucose; 45 percent are red blood cells (RBCs); and 1 percent are white blood cells (WBCs) and platelets.
RBCs (red blood cells) carry oxygen (O2) from the lungs to the organs and remove carbon dioxide (CO2) when we breathe out. Cells use O2, hydrogen (from water), and carbon (from glucose) to create energy (ATP). Think of RBCs like a car, and hemoglobin (Hb) as the protein driving it, picking up oxygen in the lungs and delivering it to tissues in the body.
Figure 2: RBCs’ main job is to carry oxygen (O2) to tissue and release the waste product, carbon dioxide (CO2), during exhalation. RBCs contain around 640 million hemoglobin molecules per cell.
Nearly all oxygen (98-99%) is carried by hemoglobin in red blood cells. Only 2% is in the blood plasma. Red blood cells also help maintain blood pH, which is vital for cell function. Hypoxia occurs when cells don’t get enough oxygen, leading to lower energy, higher acidity, and early cell death.
The RBC Distribution Width (RDW) test
The RDW test measures the size variation of red blood cells (RBCs). Normally, RBCs are similar in size, but a high RDW means some are too big or small. This leads to fewer healthy RBCs, which carry less oxygen. A high RDW is linked to anemia, higher blood acidity, and organ issues. It also signals inflammation and can predict health risks.
RDW= Standard Deviation of RBC VolumeMCV100
RDW is defined by the balance between red blood cell (RBC) production versus destruction (hemolysis).
Figure 3: A normal RDW means red blood cells (RBCs) are the same size and shape. An increased RDW (anisocytosis) shows RBCs of different sizes. This can be caused by dehydration, nutrient deficiencies (like iron or vitamin B12), stress, or poor gut bacteria. This affects RBCs’ ability to carry oxygen, leading to problems like anemia.
Red Blood Cell Life Cycle
Red blood cells (RBCs) take about seven days to mature in the bone marrow, found in bones like the skull and ribs. Immature RBCs, called reticulocytes, are bigger and still have some ribosomal RNA. Mature RBCs have a biconcave shape, no nucleus, or mitochondria. This helps them move through blood vessels, carry oxygen, and avoid using the oxygen they transport.
Figure 4: All blood cells originate from common parent cells called hematopoietic stem cells (hemocytoblasts) in the bone marrow and differentiate into myeloid progenitor cells. Hemocytoblasts are converted into premature RBCs (reticulocytes), platelets, and white blood cells (WBCs). 60 to 70 percent of stem cells are converted to WBCs, which are then converted into monocytes, lymphocytes, eosinophils, neutrophils, and basophils.
Once red blood cells (RBCs) are in the blood, the total hemoglobin (Hb) level stays the same. RBCs live for about 120 days, carrying oxygen to tissues. After they lose energy, macrophages (a type of white blood cell) break them down. The harmful byproducts are either recycled or removed from the body.
Figure 5: The Life Cycle of Red Blood Cells (RBC). Low blood oxygen (hypoxia) speeds up the breakdown of red blood cells (RBCs). Organs like the kidneys and thyroid release hormones to help the bone marrow produce RBCs using nutrients like iron, copper, and vitamins. RBCs live for about 120 days before being destroyed by macrophages from the liver, spleen, and bone marrow. The waste from RBCs is broken down: hemoglobin splits into heme and globin. Heme turns into bilirubin, which is stored or removed through stool and urine, while iron is stored or sent to the bone marrow to make new RBCs. Globin is sent to the liver for amino acid production.
Factors that Regulate RDW
Hydration
Blood plasma is mostly water (90%). Dehydration thickens the blood, making it harder for hemoglobin (Hb) to carry oxygen. It also causes cells to shrink as water moves out. The brain detects this and triggers thirst and less concentrated urine. Shrinking red blood cells (RBC) can’t carry oxygen well and die sooner. The liver then works harder to clear toxins from these damaged RBCs.
Figure 6: Water osmosis is the movement of water in and out of cells, based on the amount of solute (like salt or sugar) inside compared to outside the cell. In hypotonic cells, more solute is inside than outside, so water moves into the cell. In isotonic cells, the solute concentration is the same inside and outside, so water moves in and out equally. In hypertonic cells, there is less solute inside, so water moves out of the cell.
Figure 7: When red blood cells break down, macrophages recycle heme and iron. Proteins like haptoglobin and hemopexin help this process. Heme is broken down by an enzyme, releasing iron. The iron is either stored in organs or transported to the bone marrow to make new red blood cells. Hepcidin, a protein made by the liver, controls iron by stopping its release and reducing absorption from food.
Dehydration can happen due to:
Burns
Diarrhea
Overuse of diuretics or laxatives
Sweating from exercise or heat
Not drinking enough water
Newborns not getting enough breast milk
Blood loss from heavy periods, surgery, trauma, or frequent donations
Chronic inflammation from conditions like heart disease, cancer, or autoimmune disorders
Dehydration thickens the blood, reducing its ability to carry oxygen. This causes the body to produce more red blood cells (RBCs). While temporary situations like pregnancy can increase RBC mass, they also increase plasma volume, causing dilutional anemia.
Chronic dehydration leads to inflammation and damage to cells, causing early RBC death and higher red blood cell distribution width (RDW). Staying hydrated helps prevent anemia and keeps RDW levels normal.
Gut Microbiota
Dehydration slows blood flow to the digestive system, harming gut bacteria (dysbiosis). This affects digestion, nutrient absorption, and waste removal. Dehydration also lowers stomach acid, delays food emptying, and causes nutrient shortages that stop red blood cell production.
Figure 8: A healthy gut microbiota keeps metabolism and energy balanced. It helps with digestion, nutrient absorption, and waste removal. When the microbiota is unbalanced (dysbiosis), it can lower energy, cause inflammation, and raise harmful bacteria, proteins, and cholesterol.
Chronic dysbiosis (gut bacteria imbalance) causes undigested food particles to trigger inflammation. White blood cells (WBCs) attack these particles, releasing inflammatory proteins and heat (ROS). This thickens blood, raises blood pressure, and reduces red blood cells’ ability to carry oxygen, affecting organ function. Excess oxygen can oxidize cholesterol, causing buildup in blood vessels and contributing to atherosclerosis. Platelets and smooth muscle cells help repair by forming clots, scar tissue, and new blood vessels.
The liver breaks down food, manages energy, makes proteins, and controls ROS. When red blood cells break down, liver macrophages produce proteins that store iron and reduce iron absorption, lowering iron for red blood cell production and helping normalize RDW.
Figure 9: Atherosclerosis is the buildup of fat and scar tissue in arteries, which makes them thick and hard. This reduces blood flow, raises blood pressure, and can damage organs.
Atherosclerosis helps balance RBC production and breakdown. But long-term atherosclerosis causes inflammation, RBC clumping, and organ damage. For example, heat damage to the kidneys and thyroid reduces hormones needed for RBC production. The liver then tries to manage chronic anemia. Over time, the body can’t break down old RBCs, leading to iron buildup in the liver, pancreas, and muscles. Proper hydration and gut health are important to normalize RDW and prevent related diseases like atherosclerosis, fatty liver, and diabetes.
Clinical Significance of a High RDW
A high RDW means red blood cells (RBCs) are different sizes. This can be caused by dehydration, low thyroid or EPO levels, or nutrient deficiencies (like iron or vitamins B9 and B12). These issues result in more immature RBCs in the blood.
Immature RBCs struggle with oxygen transport. High RDW also shows higher blood acidity, which can damage cells and lower energy. This causes inflammation, leading to plaque buildup, blood clots, and new blood vessels. A high RDW signals health problems linked to inflammation and a higher risk of atherosclerosis.
Clinical Significance of a Low RDW
When RDW is low, red blood cells (RBCs) are uniform in size, which is usually normal. But it can be important in certain conditions:
Iron Deficiency Anemia: Low RDW is rare here, as this condition usually shows high RDW. However, it can happen early in iron deficiency.
Thalassemia and Blood Disorders: Dehydration and nutrient deficiencies, along with lower thyroid hormones, can reduce energy in the body. This leads to damage of RBCs and inflammation, sometimes showing low RDW with all small RBCs (microcytes).
Conclusion
Red blood cell (RBC) distribution width (RDW) helps diagnose blood issues. A high RDW may mean RBCs aren’t carrying enough oxygen, while a low RDW suggests normal RBC size. Abnormal RDW can also signal inflammation from dehydration, poor gut health, or nutrient shortages. Chronic anemia increases risks of heart disease, inflammation, metabolic problems, and other serious conditions.
Treating abnormal RDW often involves lifestyle changes, better nutrition, stress management, and supplements. These can restore normal RBC production, reducing the need for medications or transfusions. Poor diet, sleep issues, and stress can damage the gut and disrupt energy use, so a balanced approach is important for health.
Source References and Supplemental Research
Adamson JW, Finch CA. Hemoglobin function, oxygen affinity and erythropoietin. Annu Rev Physiol. 1975;37:351. [PubMed]
Bunn HF. Hemoglobin I. Structure and function. In: Beck WS, Hematology. Cambridge, MA: MIT Press, 1981;129.
Wallerstein RO. Laboratory evaluation of anemia. West J Med. 1987;146:443. [PMC free article] [PubMed]
Wang J, Klein H. Red blood cell transfusion in the treatment and management of anemia: the search for the elusive transfusion trigger. Vox Sanguinis 2010; 98: 2-11
McClellan S, Walsh T. Oxygen delivery and hemoglobin. Contin Educ Anaesth Crit Care Pain 2004; 4: 123-26,
Cappellini M, Motta I. Anemia in clinical practice –definition and classification: does hemoglobin change with aging. Semin Hematol 2015; 52: 261-69
Gao, X., Lee, H. Y., Li, W., Platt, R. J., Barrasa, M. I., Ma, Q., … & Lodish, H. F. (2017). Thyroid hormone receptor beta and NCOA4 regulate terminal erythrocyte differentiation. Proceedings of the National Academy of Sciences, 114(38), 10107-10112.
Ranney HM, Sharma V. Structure and Function of Hemoglobin. In Beutler E Lichtman M et al (eds). Willimas’s Hematology. 6th edition. McGraw Hill, 2000: 345-53.
Hoffbrand AV, Pettit JE. Essential Haematology. 3rd edition. Oxford: Blackwell, 1993: 24-25.
http://www.nlm.nih.gov/medlineplus/encyclopedia.html Medline Plus encyclopedia
LabCorp, Quest Diagnostics, Mayo Clinic Medical Laboratories, and Lab Tests Online (created by the American Association for Clinical Chemistry)
McPherson RA, Pincus MR. Henry’s Clinical Diagnosis and Management by Laboratory Methods. 23rd ed. St. Louis, MO: Elsevier; 2017.
Kaushansky K, Lichtman MA, Prchal J, et al. Williams Hematology. 9th ed. New York: McGraw-Hill; 2015.
Wintrobe MM, Greer JG, Rodgers GM, et al. Wintrobe’s Clinical Hematology. 14th ed. Philadelphia: Wolters Kluwer; 2019.
Pagana KD, Pagana TJ, Pagana TN. Mosby’s Diagnostic and Laboratory Test Reference. 15th ed. St. Louis, MO: Elsevier; 2021.
Hillman RS, Ault KA, Leporrier M, Rinder HM. Hematology in Clinical Practice. 5th ed. New York: McGraw-Hill Medical; 2010.
Hoffbrand AV, Steensma DP. Hoffbrand’s Essential Haematology. 8th ed. Hoboken, NJ: Wiley; 2020.
“Age and sex-specific lab minimum and maximum reference ranges were developed using the National Health and National Examination Survey done between 1999 to 2012 (NHANES). A major strength of our study is the large sample size of 44,328, use of numerous variables to help define a “healthy” population, and the use of piecewise regression to develop a high degree of statistical power. While other procedures for curve fitting may provide a better overall fit of the raw data, piecewise regression was chosen for this study because it objectively identifies breakpoints and, as a result, provides greater specificity.” Fulgoni VL, Agarwal S, Kellogg MD, Lieberman HR. Establishing Pediatric and Adult RBC Reference Intervals With NHANES Data Using Piecewise Regression. Am J Clin Pathol. 2019;151(2):128-142. [PubMed]
“For every 1-unit increase of RDW, there is an increased risk of occurrence of ACM (all-cause mortality) and MACEs (major adverse cardiac events). This study indicates RDW may be a prognostic indicator for CVD outcomes.” Hou H, Sun T, Li C, et al. An overall and dose-response meta-analysis of red blood cell distribution width and CVD outcomes. Sci Rep. 2017;7:43420. Published 2017 Feb 24. [PubMed]
“High RDW (≥15% variation, n = 6,050) compared to low (<12.5% n = 20,844) was strongly associated with mortality. Higher RDW was also associated with incident CAD, heart failure, peripheral vascular disease, atrial fibrillation, stroke, cancer, colorectal cancer, and especially leukemia.“ Pilling LC, Atkins JL, Kuchel GA, Ferrucci L, Melzer D. Red cell distribution width and common disease onsets in 240,477 healthy volunteers followed for up to 9 years. PLoS One. 2018;13(9):e0203504. Published 2018 Sep 13. [PubMed]
“Median RDW values varied across studies from 13.2% to 14.6%. During 68,822 person-years of follow-up of 11,827 older adults with RDW measured, there was a graded increased risk of death associated with higher RDW values (p < .001).” Patel KV, Semba RD, Ferrucci L, et al. Red cell distribution width and mortality in older adults: a meta-analysis. J Gerontol A Biol Sci Med Sci. 2010;65(3):258–265. [PubMed]
“…a strong, graded association of RDW with hsCRP and ESR independent of numerous confounding factors.” Lippi G, Targher G, Montagnana M, Salvagno GL, Zoppini G, Guidi GC. Relation between red blood cell distribution width and inflammatory biomarkers in a large cohort of unselected outpatients. Arch Pathol Lab Med 2009;133:628–32. [PubMed]
“RDW, which is recently considered as an inflammatory marker with a significant predictive value of mortality in diseased and healthy populations, is significantly higher in diabetic patients than healthy subjects and is particularly higher in uncontrolled glycemia.” Nada AM. Red cell distribution width in type 2 diabetic patients. Diabetes Metab Syndr Obes. 2015;8:525–533. Published 2015 Oct 30. [PubMed]
“Even when analyses were restricted to nonanemic participants or to those in the reference range of RDW (11%-15%) without iron, folate, or vitamin B(12) deficiency, RDW remained strongly associated with mortality. Red blood cell distribution width is a widely available test that is a strong predictor of mortality in the general population of adults 45 years or older.” Patel KV, Ferrucci L, Ershler WB, Longo DL, Guralnik JM. Red blood cell distribution width and the risk of death in middle-aged and older adults. Arch Intern Med. 2009;169(5):515–523. [PubMed]
Titcomb CP. Red Cell Distribution Width (RDW): An Underappreciated Marker for Increased Mortality. ON THE RISK Journal of The Academy of Life Underwriting. 2017;33(1):30-46. [Article] [Full Issue]
Dean L. Blood Groups and Red Cell Antigens [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2005. Chapter 1, Blood and the cells it contains.
Low red blood cell count. American Cancer Society.
https://ashpublications.org/blood/article/2/3/256/6664/DIETARY-FACTORS-CONCERNED-IN-ERYTHROPOIESIS
McPherson RA, Pincus MR. Henry’s Clinical Diagnosis and Management by Laboratory Methods. 23rd ed. St. Louis, MO: Elsevier; 2017. p. 85