What is the diagnosis and treatment for a patient with a Mean Corpuscular Hemoglobin Concentration (MCHC) of 30.9 g/dL, indicating hypochromic anemia?

Evaluation and Management of MCHC 30.9 g/dL

An MCHC of 30.9 g/dL indicates hypochromic anemia, most commonly caused by iron deficiency, though thalassemia trait, anemia of chronic disease, and rare genetic disorders of iron metabolism or heme synthesis must be excluded through systematic evaluation. 1

Initial Diagnostic Approach

Confirm Hypochromia and Assess Severity

• MCHC <32 g/dL defines hypochromic anemia, with your value of 30.9 g/dL clearly meeting this threshold 2, 3
• Obtain complete blood count with attention to:
  • MCV (microcytic if <80 fL suggests iron deficiency or thalassemia) 1, 2
  • RDW (elevated >15% favors iron deficiency over thalassemia trait) 2
  • Hemoglobin level to quantify anemia severity (men <13 g/dL, women <12 g/dL) 1

Iron Studies Are Essential

The interpretation depends critically on inflammatory status 1:

Without inflammation (normal CRP/ESR):

• Serum ferritin <30 μg/L confirms absolute iron deficiency 1
• Transferrin saturation (TSAT) <20% supports iron deficiency 1

With inflammation present:

• Ferritin 30-100 μg/L suggests combined iron deficiency and anemia of chronic disease 1
• Ferritin >100 μg/L with TSAT <20% indicates anemia of chronic disease 1
• In congestive heart failure patients specifically, ferritin >300 μg/L with low TSAT suggests inflammatory anemia 1

Advanced Iron Assessment

When standard tests are equivocal, consider 1:

• Reticulocyte hemoglobin content (CHr) <30 pg predicts response to IV iron 1
• Percent hypochromic red cells >10% confirms functional iron deficiency 1
• These specialized tests require specific equipment but offer superior sensitivity/specificity 1

Differential Diagnosis Beyond Iron Deficiency

Thalassemia Trait

Key distinguishing features from iron deficiency 2:

• MCV disproportionately low relative to degree of anemia (MCV often <75 fL)
• RDW normal or minimally elevated (versus markedly elevated in iron deficiency)
• Hemoglobin A2 >3.5% on HPLC confirms β-thalassemia trait 4
• Family history of microcytic anemia without iron deficiency 4

Genetic Sideroblastic Anemias

Consider when iron studies show paradoxical iron overload 1:

X-linked sideroblastic anemia (ALAS2 defects):

• Male predominance with microcytic hypochromic anemia and elevated ferritin/TSAT 1, 5
• Bone marrow shows ring sideroblasts 5
• May respond to pyridoxine (vitamin B6) 50-200 mg daily 1

SLC25A38 defects:

• Severe transfusion-dependent anemia presenting in childhood 1
• Ring sideroblasts with elevated ferritin before transfusions 1
• Hematopoietic stem cell transplantation is only curative option 1

DMT1 defects (SLC11A2):

• Microcytic anemia with paradoxically increased TSAT 1
• Liver iron loading despite normal/low ferritin—requires MRI screening 1

Treatment Algorithm

Iron Deficiency Anemia (Most Common)

Oral iron therapy:

• 200 mg elemental iron daily for non-dialysis patients 1
• Inadequate for hemodialysis patients due to ongoing losses 1
• Preoperative correction within 2-4 weeks reduces transfusion needs and complications 1

Intravenous iron indications 1:

• Hemodialysis patients (oral iron insufficient) 1
• Heart failure patients with ferritin <100 μg/L or ferritin 100-300 μg/L with TSAT <20% 1
• Intolerance or malabsorption of oral iron 1
• Ferric carboxymaltose improved functional capacity and quality of life in heart failure trials 1

Anemia of Chronic Disease

• Treat underlying inflammatory condition 1
• IV iron may benefit despite elevated ferritin if TSAT <20% 1
• Erythropoiesis-stimulating agents reserved for specific conditions (CKD, heart failure) 1

Thalassemia Trait

• No treatment required—avoid unnecessary iron supplementation 2, 4
• Genetic counseling for reproductive planning 4

Critical Pitfalls to Avoid

• Never assume iron deficiency without checking ferritin and TSAT—thalassemia trait mimics iron deficiency but iron therapy is contraindicated 2, 4
• Ferritin is an acute phase reactant—values 30-100 μg/L are ambiguous in inflammatory states and may mask true iron deficiency 1
• Normal ferritin does not exclude liver iron overload in genetic disorders—MRI surveillance needed for DMT1 defects 1
• Hypochromic anemia predicts mortality independent of hemoglobin level—particularly in heart failure (HR 1.7 for all-cause mortality) 3
• Screen for occult GI bleeding in iron deficiency without obvious source—especially in non-menstruating patients 1