When is erythrocytosis diagnosed in a male?

Diagnosis of Erythrocytosis in Males

Erythrocytosis in males is diagnosed when hemoglobin is >16.5 g/dL, hematocrit is >49%, or there is increased red cell mass (>25% above mean normal predicted value). 1

Diagnostic Criteria

The diagnosis of erythrocytosis is based on laboratory parameters that indicate an increased red cell volume:

• Major criteria for diagnosis:
  • Hemoglobin >16.5 g/dL in men
  • OR Hematocrit >49% in men
  • OR Increased red cell mass (>25% above mean normal predicted value) 1

Differentiating Types of Erythrocytosis

Once erythrocytosis is established, the next step is to determine whether it is:

1. Primary erythrocytosis (Polycythemia Vera)

   • Requires meeting either:
     • All 3 major criteria: elevated hemoglobin/hematocrit/RCM, bone marrow showing hypercellularity with trilineage growth, and presence of JAK2 mutation
     • OR first 2 major criteria plus subnormal serum EPO level 1

2. Secondary erythrocytosis

   • Results from external stimuli to the bone marrow causing increased red cell production 2
   • Normal or elevated erythropoietin levels (unlike PV where EPO is typically low)

Diagnostic Algorithm

1. Confirm erythrocytosis:

   • Hemoglobin >16.5 g/dL OR
   • Hematocrit >49% OR
   • Increased red cell mass (>25% above predicted)

2. Measure serum erythropoietin level:

   • Low EPO → suggests primary erythrocytosis (PV)
   • Normal/elevated EPO → suggests secondary erythrocytosis 3

3. For suspected primary erythrocytosis (PV):

   • Test for JAK2 V617F or JAK2 exon 12 mutations
   • Consider bone marrow biopsy showing hypercellularity with trilineage growth 1

4. For suspected secondary erythrocytosis:

   • Evaluate for common causes:
     • Hypoxic conditions (sleep apnea, COPD, smoking)
     • Medication-induced (testosterone therapy, SGLT-2 inhibitors) 4
     • Post-renal transplant erythrocytosis 5
     • Congenital causes (especially in younger patients with family history) 3

Important Considerations

• In patients on testosterone therapy, erythrocytosis is a common side effect with rates up to 66.7%, particularly with intramuscular formulations 4
• Testosterone therapy requires regular monitoring of hemoglobin/hematocrit at baseline, 1-2 months after initiation, every 3-6 months during the first year, and annually thereafter 6
• When evaluating erythrocytosis, consider iron deficiency which may mask true hemoglobin/hematocrit levels 1
• For research or clinical trials, a formal PV diagnosis requires demonstration of meeting the WHO criteria in terms of hemoglobin/hematocrit level after iron replacement 1

Clinical Pitfalls to Avoid

• Don't overlook the possibility of medication-induced erythrocytosis, especially in patients on testosterone therapy or SGLT-2 inhibitors 4
• Don't diagnose PV without checking JAK2 mutation status and erythropoietin levels
• Don't forget to evaluate for hypoxic conditions in patients with secondary erythrocytosis
• Be aware that normal hematocrit levels vary between men (42%-54%) and women (38%-46%), so target levels may need individualization in certain clinical scenarios 1

By following this structured approach, clinicians can accurately diagnose erythrocytosis in male patients and determine the appropriate classification to guide management decisions.