Management of High Hemoglobin Levels in Adults
For adults with elevated hemoglobin, immediately investigate for polycythemia vera by testing for JAK2 mutations and measuring serum erythropoietin levels, then initiate therapeutic phlebotomy to maintain hematocrit <45% if polycythemia vera is confirmed. 1
Diagnostic Thresholds for Elevated Hemoglobin
Elevated hemoglobin requiring investigation is defined as:
- Men: Hemoglobin >16.5 g/dL (hematocrit >49%) 1, 2
- Women: Hemoglobin >16.0 g/dL (hematocrit >48%) 1, 2
These thresholds were established in the 2016 WHO classification revision to capture "masked polycythemia vera" cases that were previously missed, as delayed diagnosis leads to worse outcomes. 2
Initial Diagnostic Workup
When hemoglobin exceeds these thresholds, perform the following tests immediately:
- Complete blood count with differential to assess for thrombocytosis (present in 53% of PV cases) and leukocytosis (present in 49% of PV cases) 1
- JAK2 mutation testing - present in >95% of polycythemia vera cases and distinguishes primary from secondary causes 1
- Serum erythropoietin level - helps differentiate polycythemia vera (low EPO) from secondary erythrocytosis (elevated EPO) 3
- Chest radiograph to evaluate for pulmonary causes of secondary erythrocytosis 4
If JAK2 is negative and clinical suspicion remains high, consider red blood cell mass and plasma volume measurements to differentiate true polycythemia from relative polycythemia (decreased plasma volume). 4
Risk Stratification for Thrombosis
Once polycythemia vera is diagnosed, stratify thrombotic risk immediately:
High-risk patients (require cytoreductive therapy):
- Age ≥60 years, OR
- Prior thrombotic event (arterial thrombosis occurs in 16% at diagnosis, venous thrombosis in 7%) 1, 5
Low-risk patients (phlebotomy and aspirin only):
Additional risk factors that increase thrombotic risk include hypertension, smoking, and leukocytosis, though these are not formally included in risk scoring. 2
Immediate Management
All Patients with Polycythemia Vera
Therapeutic phlebotomy is mandatory to maintain hematocrit <45% - this target reduces thrombotic complications and is non-negotiable. 1, 5
Low-dose aspirin should be initiated unless contraindicated (particularly avoid if platelet count ≥1000 × 10⁹/L due to acquired von Willebrand disease and bleeding risk). 1
High-Risk Patients
Add cytoreductive therapy to phlebotomy and aspirin:
Critical Pitfalls to Avoid
Do not target "normal" hemoglobin ranges in polycythemia vera management - the goal is hematocrit <45%, not normalization to population means. Studies attempting to maintain normal hematocrit showed increased thrombotic complications. 5
Do not delay phlebotomy while awaiting genetic testing results - if clinical suspicion is high and hematocrit is elevated, begin phlebotomy immediately as thrombosis is the leading cause of morbidity and mortality. 1
Watch for unusual thrombotic sites - venous thromboses in polycythemia vera can involve splanchnic veins (hepatic, portal, mesenteric), which are uncommon in other conditions. 1
Long-Term Monitoring
Patients with polycythemia vera face cumulative risks over time:
- Myelofibrosis progression: 12.7% 1
- Acute myeloid leukemia transformation: 6.8% 1
- Median survival: 14.1-27.6 years from diagnosis 1
Regular monitoring for disease progression and complications is essential throughout the patient's lifetime.
Context-Specific Considerations
In chronic kidney disease patients, the approach differs entirely - elevated hemoglobin in CKD patients receiving ESA therapy should not exceed 13.0 g/dL, and ESA doses should be decreased rather than initiating phlebotomy. 6 This represents a completely different clinical scenario from primary polycythemia.
In cancer patients receiving ESAs, therapy should not be initiated when hemoglobin ≥10 g/dL due to increased mortality risk, and this population requires different management algorithms. 6