Management of Elevated Hematocrit with Macrocytosis and Low MCHC
This patient requires immediate assessment for dehydration as the most likely cause of the mildly elevated hematocrit (46.7%), followed by evaluation for early iron deficiency given the low MCHC (30.6 g/dL), and consideration of alcohol use or B12/folate deficiency given the elevated MCV (107 fL). 1
Initial Clinical Assessment
The combination of findings suggests multiple concurrent processes rather than a single diagnosis:
- Elevated hematocrit (46.7%) is minimally above normal and most commonly represents relative polycythemia from plasma volume depletion rather than true erythrocytosis 1, 2
- Elevated MCV (107 fL) indicates macrocytosis, which requires investigation for alcohol use, vitamin B12 deficiency, folate deficiency, hypothyroidism, or liver disease 3
- Low MCHC (30.6 g/dL) suggests hypochromia, typically indicating early iron deficiency before microcytosis develops 1, 2
- Normal hemoglobin (14.3 g/dL) and RBC count (4.38) argue against true polycythemia vera, which would require hemoglobin >16.5 g/dL in men or >16.0 g/dL in women 4
Immediate Diagnostic Workup
First-Line Testing
Assess hydration status clinically by examining mucous membranes, skin turgor, orthostatic vital signs, and reviewing recent fluid intake, diuretic use, and fluid losses 1, 2. Dehydration is the most common cause of relative polycythemia with hematocrit values in this range 1, 5.
Order iron studies immediately including serum ferritin, iron, total iron binding capacity, and transferrin saturation to evaluate for iron deficiency 3, 1, 2. The low MCHC with normal MCV represents early iron deficiency before microcytosis manifests 1.
Obtain vitamin B12 and folate levels to investigate the macrocytosis 3. The MCV of 107 fL is significantly elevated and requires explanation.
Check thyroid function (TSH) as hypothyroidism commonly causes macrocytosis 3.
Obtain comprehensive metabolic panel to assess renal function and electrolytes, particularly if dehydration is suspected 2.
Second-Line Testing (If Initial Workup Non-Diagnostic)
Repeat CBC after ensuring adequate hydration to determine if the elevated hematocrit persists 1, 2. If hematocrit normalizes with hydration, this confirms relative polycythemia 1, 5.
If hematocrit remains elevated despite adequate hydration, consider:
- Erythropoietin level to differentiate primary from secondary causes 2
- JAK2 mutation testing (V617F and exon 12) only if hemoglobin exceeds diagnostic thresholds for polycythemia vera 3, 4, 6
- Evaluation for secondary causes including smoking history, sleep apnea, chronic lung disease, and carbon monoxide exposure 2, 4
Management Algorithm
Step 1: Address Dehydration (If Present)
Increase oral fluid intake or provide intravenous fluids if the patient cannot tolerate oral hydration 1. Address underlying causes of fluid loss including diuretic adjustment, diarrhea, vomiting, or inadequate intake 1, 2.
Step 2: Manage Iron Deficiency (If Confirmed)
Initiate oral iron supplementation (typically ferrous sulfate 325 mg daily to three times daily) if iron deficiency is confirmed 3.
Investigate the source of iron deficiency including:
- Gastrointestinal blood loss (consider colonoscopy and upper endoscopy in appropriate patients)
- Menstrual blood loss in premenopausal women
- Dietary insufficiency
- Malabsorption 3
Step 3: Treat Macrocytosis Based on Etiology
If B12 deficiency is confirmed, initiate vitamin B12 supplementation (typically 1000 mcg intramuscularly or 1000-2000 mcg orally daily) 3.
If folate deficiency is confirmed, provide folic acid 1 mg daily 3.
If alcohol use is identified, counsel on reduction or cessation and provide appropriate support 2.
If hypothyroidism is confirmed, initiate thyroid hormone replacement 3.
Step 4: Phlebotomy Considerations
Phlebotomy is NOT indicated in this patient 3, 4. The hematocrit of 46.7% is only minimally elevated, and therapeutic phlebotomy is reserved for:
- Confirmed polycythemia vera with hematocrit target <45% 3, 4, 6
- Hemoglobin >20 g/dL and hematocrit >65% with hyperviscosity symptoms 2
Avoid inappropriate phlebotomy as it risks worsening iron deficiency and does not address the underlying causes in this patient 2.
Critical Pitfalls to Avoid
Do not diagnose polycythemia vera based on this CBC alone. The hemoglobin (14.3 g/dL) and hematocrit (46.7%) do not meet diagnostic criteria, which require hemoglobin >16.5 g/dL in men or >16.0 g/dL in women 4, 6.
Do not overlook coexisting iron deficiency in patients with elevated hematocrit. The low MCHC is a critical finding requiring investigation and treatment 1, 2.
Do not perform aggressive phlebotomy without confirming true polycythemia, as this can worsen iron deficiency and cause harm 2.
Do not ignore the macrocytosis. An MCV of 107 fL requires investigation for B12 deficiency, folate deficiency, alcohol use, hypothyroidism, or liver disease, as these conditions have significant clinical implications 3, 2.
Do not assume a single diagnosis explains all abnormalities. This patient likely has multiple concurrent processes (relative polycythemia from dehydration, early iron deficiency, and a cause of macrocytosis) that each require specific management 1, 2.
Follow-Up Monitoring
Repeat CBC in 2-4 weeks after addressing hydration and initiating iron supplementation to assess response 1, 2.
Monitor iron studies after 4-8 weeks of iron supplementation to confirm improvement 3.
Reassess hematocrit after ensuring adequate hydration. If it normalizes, no further evaluation for polycythemia is needed 1, 2.
If hematocrit remains elevated (>49% in men or >48% in women) despite adequate hydration and normal iron stores, proceed with evaluation for true polycythemia including JAK2 testing and hematology referral 2, 4, 6.