Instalab ResearchThe causes of normocytic anemia are broad and often intertwined. Clinical studies have identified several consistent culprits.
Chronic Disease and Inflammation: One of the most common causes is what doctors call “anemia of chronic disease.” Longstanding conditions such as infections, autoimmune disorders, or cancer interfere with the way the body uses iron and suppress the bone marrow’s ability to make red blood cells. Even though the iron may be present in the body, inflammation makes it unavailable for use. In older adults, chronic disease and inflammation account for a large portion of cases.
Chronic Kidney Disease: The kidneys play a vital role in red blood cell production by releasing a hormone called erythropoietin, which stimulates the bone marrow. In chronic kidney disease, the production of this hormone drops, leading to anemia. This anemia is almost always normocytic in nature and is one of the defining complications of kidney failure. Treatments targeting erythropoietin deficiency have been shown to significantly improve hemoglobin levels and quality of life.
Iron Deficiency in Disguise: Although iron deficiency usually leads to microcytic anemia, research has shown it can also present as normocytic. Many patients with normocytic anemia respond to iron supplementation even when their ferritin levels appear normal. This challenges the assumption that iron deficiency can be ruled out based solely on standard lab thresholds.
Vitamin B12 and Folate Deficiency: Deficiencies in vitamin B12 or folate usually cause macrocytic anemia. However, a significant proportion of patients with normocytic anemia are found to have low levels of these vitamins. Some improve with replacement therapy, underscoring the importance of testing for these nutrients even when red blood cell size looks normal.
Diabetes and Metabolic Disorders: Diabetes is increasingly recognized as a contributor to normocytic anemia, particularly in older patients. Poor blood sugar control may shorten red blood cell survival, and correcting glucose levels can improve hemoglobin. Studies show that older age is an independent risk factor for normocytic anemia in diabetes.
Cancer and Systemic Inflammation: Cancer is another setting where normocytic anemia is prevalent. In gastrointestinal cancers, more than half of patients present with normocytic anemia, strongly associated with systemic inflammation. These patients also require more transfusions and are at higher risk of complications such as infections.
Cardiovascular Disease: In patients with coronary artery disease and heart failure, normocytic anemia is particularly concerning. It worsens fatigue, breathlessness, and overall prognosis. In older patients with heart disease, anemia is very often normocytic, reflecting the combined impact of chronic disease and comorbidities.
Not all normocytic anemia is life-threatening, but it is rarely meaningless. For some patients, especially older adults with diabetes, it may be mild and stable without significantly affecting survival or quality of life. For others, it may be the first sign of an undiagnosed condition such as kidney disease, inflammatory illness, or cancer. The important message is that normocytic anemia is not a diagnosis to ignore. It requires evaluation to uncover what is driving it.
Treatment depends on the cause, but clinical research has clarified several effective strategies:
For many patients, living with normocytic anemia means staying alert to the underlying condition driving it. Regular monitoring, following treatment plans, and keeping chronic conditions under control are key. Because normocytic anemia can sometimes precede a more serious diagnosis, follow-up is essential rather than optional.
