Automated red blood cell counts and hematocrit values can be misleading when assessing the total red blood cell mass in individuals with polycythemia vera (PV). Direct measurement of red blood cell mass is crucial for accurate diagnosis, revealing an increase alongside normal or slightly reduced plasma volume. This specialized nuclear medicine test employs radiochromium-labeled red blood cells to precisely measure red blood cell and plasma volume. However, in cases where hemoglobin concentrations reach 20 g/dL or hematocrit values exceed 60% in males and 56% in females, an elevated red blood cell mass is invariably present, simplifying the polycythemia diagnosis.
In PV patients, red blood cells typically appear normochromic and normocytic. However, conditions like peptic ulcer disease or phlebotomy treatment can lead to hypochromic and microcytic cells due to iron depletion.
Several findings, while not mandatory for a polycythemia diagnosis, are frequently observed in PV patients [1]. These include:
Common Findings in Polycythemia Vera
- Thrombocytosis: A platelet count exceeding 400,000 platelets/µL is a common indicator.
- Leukocytosis: A white blood cell count above 12,000/µL is another frequent finding in polycythemia diagnosis.
- Elevated Leukocyte Alkaline Phosphatase (LAP) Score: A score greater than 100 units/L in the absence of fever or infection is often observed.
Detailed Hematological Features
Thrombocytosis: Elevated platelet counts, ranging from 400,000 to 800,000/µL, are found in about half of PV patients. An interesting artifact, pseudohyperkalemia, can occur in serum due to potassium release from increased platelets during in vitro coagulation. However, true plasma potassium levels remain normal in vivo, confirmed by plasma measurements and the absence of ECG changes. Platelet morphology may also be abnormal, featuring macrothrombocytes and granule-deficient platelets.
Leukocytosis: An elevated white blood cell count (> 12,000/µL) is present in approximately 60% of polycythemia patients. This primarily involves neutrophils with a left shift and some immature cells. Mild basophilia is also seen in 60% of cases, contributing to Polycythemia Diagnosis Criteria.
Leukocyte Alkaline Phosphatase (LAP) Score: The LAP score is elevated (> 100 U/L) in 70% of PV patients. It’s important to note that this technique is semiquantitative and prone to errors between observers and labs unless flow cytometry is used, which is not standard practice.
Platelet Function and Coagulation: Abnormal platelet function, detectable through aggregation tests with epinephrine, ADP, or collagen, can be present, although bleeding time might be normal. Spontaneous platelet aggregation in platelet-rich plasma without additives suggests a predisposition to thromboses. Routine coagulation test results are typically normal, despite a high fibrinogen turnover rate. However, prothrombin time (PT) and activated partial thromboplastin time (aPTT) may be artificially prolonged due to the high red blood cell volume reducing plasma relative to anticoagulant in test tubes. Adjusting the anticoagulant-to-blood ratio is necessary for accurate coagulation tests in polycythemic patients, which is crucial for proper polycythemia diagnosis and management.
Vitamin B12 and Hyperuricemia: Vitamin B12 levels exceed 900 pg/mL in around 30% of patients, and 75% show elevated unbound vitamin B12 binding capacity (> 2200 pg/mL). This is due to increased transcobalamin III, a white blood cell binding protein, reflecting total white blood cell counts in peripheral blood and bone marrow, which aids in polycythemia diagnosis. Hyperuricemia occurs in 40% of patients, indicating high bone marrow cell turnover and DNA metabolite release.
Key Diagnostic Tests for Polycythemia Vera
The most critical diagnostic tests for polycythemia vera are:
- JAK2 Mutation Analysis: Detecting the JAK2 V617F mutation is paramount in confirming PV.
- Serum Erythropoietin (Epo) Level: Measuring serum Epo level is crucial. A positive JAK2 V617F mutation combined with a low Epo level firmly establishes a polycythemia diagnosis of PV.
A low serum Epo level, found in almost all PV patients without recent hemorrhage, differentiates polycythemia vera from secondary polycythemia. In secondary causes, Epo levels are generally normal or elevated. It is important to consider laboratory-specific reference ranges for serum Epo levels in polycythemia diagnosis.
Endogenous Erythroid Colony (EEC) Formation & IGF-1R: Endogenous erythroid colony (EEC) formation was previously a minor diagnostic criterion but was removed from the WHO classification in 2016 due to its complexity. Insulinlike growth factor 1 receptor (IGF-1R) measurement has been proposed as a substitute. Studies show IGF-1R’s role in EEC formation in PV, with significantly higher IGF-1R levels in PV patients compared to secondary polycythemia and normal controls. This suggests IGF-1R as a potential marker in polycythemia diagnosis, particularly differentiating PV from other polycythemic conditions.
