What does an elevated RBC count with low MCH and MCHC but normal hemoglobin and hematocrit signify, and how should it be managed?

Evaluation of Elevated RBC with Low MCH/MCHC and Normal Hemoglobin/Hematocrit

This pattern most likely represents early iron deficiency anemia that is being masked by concurrent secondary erythrocytosis, and you should immediately obtain iron studies (serum ferritin, transferrin saturation, and serum iron) to confirm iron deficiency before it progresses to overt anemia. 1

Understanding This Laboratory Pattern

The combination of elevated RBC count (5.62, above the upper limit of 5.28) with low MCH (25.4, below 26.6) and low MCHC (31.2, below 31.5) alongside normal hemoglobin and hematocrit creates a paradoxical picture that requires careful interpretation:

• The elevated RBC count indicates erythrocytosis - the bone marrow is producing more red blood cells than normal, which could be compensatory or pathological 2

• The low MCH and MCHC indicate iron-deficient erythropoiesis - each individual red blood cell contains less hemoglobin than normal, which is the hallmark of iron deficiency even before anemia develops 1

• The elevated RDW (15.1, at upper limit of normal) supports this interpretation - it reflects a mixed population of normal-sized older cells and smaller, hypochromic newer cells coexisting in circulation 1

• The normal hemoglobin and hematocrit are misleading - they appear "normal" only because the increased number of red blood cells compensates for the reduced hemoglobin content per cell 1

Immediate Diagnostic Workup

Order the following tests immediately:

• Serum ferritin - values <30 μg/L confirm iron deficiency in the absence of inflammation 1

• Transferrin saturation - values <15-16% support iron deficiency and are less affected by inflammation than ferritin 1

• Serum iron and total iron-binding capacity - to complete the iron panel 1

• C-reactive protein (CRP) - to assess for inflammation that could falsely elevate ferritin 2

• Reticulocyte count - to evaluate bone marrow response 1

Important caveat: MCH is actually more reliable than MCHC for detecting iron deficiency because it is less dependent on storage conditions and the counting machine used, and a reduction occurs in both absolute and functional iron deficiency 1. In your patient, both are reduced, strengthening the suspicion for iron deficiency.

Clinical Significance and Underlying Causes

You must investigate why this patient has both erythrocytosis AND iron deficiency:

Potential causes of the erythrocytosis component:

• Chronic hypoxemia - from smoking, chronic lung disease, obstructive sleep apnea, or cyanotic heart disease 3, 2

• Testosterone use - either prescribed or unprescribed, which is common in young adults 2

• High altitude residence - physiologic adaptation can increase RBC count 2

• Early polycythemia vera - though less likely given the iron deficiency pattern 4

Potential causes of the iron deficiency component:

• Chronic blood loss - gastrointestinal bleeding is the most common cause in adults, particularly in men and postmenopausal women 1

• Menstrual losses - in premenopausal women 1

• Dietary insufficiency - though less common as a sole cause in developed countries 1

• Malabsorption - from celiac disease, inflammatory bowel disease, or gastric surgery 1

Critical point: In cyanotic congenital heart disease patients, iron deficiency is frequently encountered and causes reduction of hemoglobin without proportional change in hematocrit, compromising systemic oxygen transport 3. This same principle applies to any cause of secondary erythrocytosis.

Management Algorithm

Step 1: Confirm Iron Deficiency

• If ferritin <30 μg/L and transferrin saturation <15-16%, iron deficiency is confirmed 1

• If ferritin is 30-100 μg/L with elevated CRP, iron deficiency may still be present despite inflammation falsely elevating ferritin 1

Step 2: Investigate the Cause of Iron Deficiency

• In adult men and postmenopausal women: Assume gastrointestinal bleeding until proven otherwise and refer for endoscopic evaluation 1

• In premenopausal women: Assess menstrual history, but still consider GI evaluation if losses seem inadequate to explain the deficiency 1

• In all patients: Take detailed history regarding diet, medications (NSAIDs, anticoagulants), and symptoms of malabsorption 1

Step 3: Investigate the Cause of Erythrocytosis

• Assess for hypoxic causes:

  • Smoking history and carbon monoxide exposure 2
  • Symptoms of sleep apnea (snoring, daytime somnolence, witnessed apneas) 2
  • History of chronic lung disease 2
  • History of cyanotic congenital heart disease 3

• Assess for non-hypoxic causes:

  • Testosterone use (prescribed or supplements) 2
  • Altitude of residence 2
  • Symptoms suggesting polycythemia vera (aquagenic pruritus, erythromelalgia, splenomegaly) 4

Step 4: Treat the Iron Deficiency

Once iron deficiency is confirmed, initiate oral iron supplementation:

• Standard dosing: Oral ferrous sulfate 325 mg (65 mg elemental iron) once to three times daily 1

• Monitor closely: Recheck CBC and iron studies in 4-6 weeks 1

• Critical warning: In patients with underlying erythrocytosis, iron repletion can cause rapid increases in hemoglobin and hematocrit, potentially increasing thrombotic risk 3, 2. Monitor hemoglobin closely and avoid rapid increases >0.3 g/dL per week 2

Step 5: Manage the Erythrocytosis

• If secondary to hypoxemia: Treat the underlying condition (smoking cessation, CPAP for sleep apnea, optimize lung disease management) 2

• If secondary to testosterone: Consider dose reduction or temporary discontinuation 2

• If polycythemia vera is suspected: Order JAK2 mutation testing (exon 14, then exon 12 if negative) and refer to hematology if positive 4

• Phlebotomy is NOT indicated at this hemoglobin level (14.3 g/dL) and hematocrit (45.9%) - therapeutic phlebotomy is only indicated when hemoglobin >20 g/dL and hematocrit >65% with symptoms of hyperviscosity 3, 2

Common Pitfalls to Avoid

• Don't dismiss the low MCH/MCHC as insignificant just because hemoglobin and hematocrit are "normal" - this represents evolving iron deficiency that will progress to overt anemia if untreated 1

• Don't perform phlebotomy in this patient - the hemoglobin and hematocrit are not elevated enough to warrant it, and phlebotomy would worsen the iron deficiency 3, 2

• Don't rely on MCV alone to screen for iron deficiency in the setting of erythrocytosis - MCV is unreliable in this context, and you must obtain serum ferritin, transferrin saturation, and iron levels 3

• Don't ignore the erythrocytosis once you confirm iron deficiency - you must still investigate and address the underlying cause of the elevated RBC count 2

• Don't replicate iron too rapidly - in patients with underlying erythrocytosis, rapid iron repletion can cause dangerous increases in red cell mass and thrombotic risk 3, 2