Can Low Hemoglobin Be Caused by Illness?
Yes, low hemoglobin is frequently caused by underlying illnesses, particularly chronic kidney disease, cancer, gastrointestinal disorders causing blood loss, and chronic inflammatory conditions that impair iron utilization or erythropoiesis.
Primary Disease-Related Causes of Low Hemoglobin
Chronic Kidney Disease as a Major Cause
Anemia develops consistently when kidney function declines below a GFR of 60 mL/min/1.73 m² (CKD stage 3), with prevalence increasing dramatically at later stages 1.
The prevalence of anemia increases from relatively low levels in CKD stages 1-2 to 22.2% in stage 4 and 52.4% in stage 5 among high-risk patients 1.
In patients with diabetes and CKD, anemia is more prevalent, more severe, and occurs earlier in the disease course compared to non-diabetic CKD patients—affecting 8.7% versus 6.9% in stage 2, and 22.2% versus 7.9% in stage 4 1.
The mechanism involves reduced erythropoietin production by failing kidneys, combined with uremic toxins that suppress bone marrow function 1.
Cancer-Related Anemia
Cancer causes anemia through multiple mechanisms: bone marrow infiltration by malignant cells, bleeding from tumors, hypersplenism, hemolysis, and anemia of chronic disease 1.
Chemotherapy and extensive radiotherapy directly cause bone marrow suppression and renal toxicity, leading to treatment-related anemia 1.
Anemia in cancer patients constitutes a negative prognostic factor for overall survival in most cancer types and significantly impacts quality of life 1.
Gastrointestinal and Blood Loss Disorders
Chronic blood loss from gastrointestinal sources (ulcers, malignancies, inflammatory bowel disease) leads to iron deficiency anemia, which is a common cause of low hemoglobin 1, 2.
Evaluation should include assessment for occult blood loss in stool and urine when investigating unexplained anemia 1.
Defining Anemia Thresholds by Clinical Context
General Population Thresholds
Anemia should be diagnosed at hemoglobin <13.5 g/dL in adult males and <12.0 g/dL in adult females 1.
These thresholds represent approximately the fifth percentile of the healthy population and indicate the need for further evaluation 1.
CKD-Specific Thresholds
In CKD patients, anemia workup should be initiated when hemoglobin falls below 12 g/dL in adult males and postmenopausal females, or below 11 g/dL in premenopausal females and prepubertal patients 1.
These lower thresholds in CKD reflect the understanding that hemoglobin at the lowest fifth percentile may signify significant nutritional deficits, systemic illness, or disorders requiring attention 1.
Cancer Patient Thresholds
- Mild anemia is defined as hemoglobin ≤11.9 g/dL and ≥10 g/dL, moderate anemia as ≤9.9 and ≥8.0 g/dL, and severe anemia as <8.0 g/dL 1.
Clinical Implications and Surveillance
Monitoring Requirements
All CKD patients require hemoglobin measurement at least annually, with more frequent surveillance needed for those with greater disease burden, unstable clinical course, or evidence of previous hemoglobin decline 1.
The natural history of anemia in CKD without treatment shows gradual decline in hemoglobin over time, necessitating regular monitoring 1.
Mortality and Morbidity Associations
In heart failure patients, hemoglobin levels below 13 g/dL are independently associated with increased mortality risk: adjusted hazard ratio of 1.50 for hemoglobin 11.0-11.9 g/dL, 1.89 for 10.0-10.9 g/dL, and 3.48 for <9.0 g/dL 3.
Anemia in CKD patients is associated with left ventricular hypertrophy, which increases death risk 2.9-fold 1.
Hemoglobin variability itself is associated with increased mortality risk in CKD patients, even in those not receiving erythropoiesis-stimulating agents 4.
Common Pitfalls to Avoid
Do not assume lower hemoglobin levels in older males are normal—a substantial fraction of older males with low hemoglobin show concurrent evidence of pathological conditions 1.
Chronic inflammatory states may mask iron deficiency by falsely elevating serum ferritin, requiring assessment of transferrin saturation alongside ferritin 5, 2.
In CKD patients, functional iron deficiency (adequate stores but insufficient availability) differs from absolute iron deficiency and requires different diagnostic criteria: transferrin saturation ≤20% with elevated ferritin indicates functional deficiency 2.
Hemoglobin measured post-dialysis may be falsely elevated compared to pre-dialysis values; always use pre-dialysis samples for monitoring dialysis patients 1.