Low MCHC with Elevated RDW: Diagnostic Significance
The combination of low MCHC with elevated RDW strongly indicates iron deficiency anemia and warrants immediate investigation for the underlying cause, particularly gastrointestinal blood loss in adult men and postmenopausal women. 1
Primary Diagnostic Interpretation
This laboratory pattern represents microcytic, hypochromic anemia with significant red cell size variation, which is the hallmark of iron deficiency anemia. 1 The elevated RDW (>14.0%) reflects heterogeneous red blood cell populations and is an early indicator of iron deficiency, often appearing before MCV changes become apparent. 2, 1
Key Distinguishing Features
- Iron deficiency characteristically presents with elevated RDW due to the presence of both older normocytic cells and newer microcytic cells in circulation, creating size heterogeneity. 2, 3
- This pattern effectively excludes thalassemia trait, which typically shows normal or only slightly elevated RDW with homogeneous microcytic cells. 2, 1
- Low MCHC specifically indicates reduced hemoglobin concentration within red cells (hypochromia), a finding strongly associated with iron deficiency. 1, 4
Essential Diagnostic Workup
First-Line Laboratory Tests
- Serum ferritin (<30 μg/L confirms iron deficiency in the absence of inflammation; <100 μg/L with concurrent inflammation) is the most powerful confirmatory test. 1
- Transferrin saturation (<30% supports iron deficiency diagnosis). 1
- C-reactive protein (CRP) to identify inflammation that may falsely elevate ferritin levels. 1
- Reticulocyte count to assess bone marrow response to anemia. 1
Critical Caveat About Ferritin
Serum ferritin can be falsely elevated in inflammatory conditions, chronic disease, malignancy, or liver disease, potentially masking true iron deficiency—always interpret ferritin in context with CRP and transferrin saturation. 1
Mandatory Clinical Investigation
All adult men and postmenopausal women with confirmed iron deficiency require both upper and lower endoscopy to exclude malignancy, regardless of anemia severity. 2 Even mild anemia warrants investigation, as severity does not correlate with likelihood of serious underlying disease. 2
Additional Considerations
- Investigate for gastrointestinal blood loss as the primary source in these populations. 2, 1
- Consider combined deficiencies (iron plus folate or B12), which can result in normal MCV despite iron deficiency but would still show elevated RDW. 2
- In women of childbearing age, assess menstrual blood loss and dietary intake. 4
Treatment Approach
- Initiate iron supplementation (oral or intravenous) once iron deficiency is confirmed by ferritin testing. 2
- Do not empirically treat with iron before confirming iron deficiency, as this can cause iron overload in misdiagnosed thalassemia patients. 2
- Address the underlying cause of iron loss while replacing iron stores. 2
Diagnostic Performance
RDW demonstrates high sensitivity (82.3%) and specificity (97.4%) for detecting iron deficiency, superior to MCV, MCH, or MCHC alone in early detection. 3 The combination of low MCHC with elevated RDW provides positive and negative predictive values of approximately 48-51% and 80-85% respectively for identifying impaired iron transport. 5