What is the best way to rule out polycythemia (excessive red blood cell count)?

From the Guidelines

The best way to rule out polycythemia is through a complete blood count (CBC) with specific attention to hemoglobin, hematocrit, and red blood cell count, followed by testing for JAK2 V617F mutation and measuring erythropoietin levels, as recommended by the most recent guidelines 1. To rule out polycythemia, the following steps should be taken:

• Perform a CBC to evaluate hemoglobin, hematocrit, and red blood cell count. If these values are elevated (hemoglobin >16.5 g/dL in men or >16.0 g/dL in women, hematocrit >49% in men or >48% in women), further testing is necessary.
• Test for JAK2 V617F mutation, which is present in about 95% of polycythemia vera cases, as this is a key diagnostic criterion 1.
• Measure erythropoietin levels, which are typically low in polycythemia vera but elevated in secondary polycythemia, to help differentiate between primary and secondary polycythemia.
• Consider additional tests, such as:
  • Arterial blood gas analysis to assess oxygen saturation
  • Abdominal ultrasound to evaluate spleen size
  • Specialized tests like red cell mass measurement using chromium-51 labeling in unclear cases These tests help differentiate between primary polycythemia (polycythemia vera), secondary polycythemia (due to hypoxia or abnormal erythropoietin production), and relative polycythemia (due to plasma volume reduction). Early diagnosis is crucial, as polycythemia increases the risk of thrombotic events and can progress to myelofibrosis or leukemia if left untreated, highlighting the importance of prompt and accurate diagnosis 1.

From the Research

Ruling Out Polythycemia

To rule out polythycemia, several steps and considerations must be taken into account:

• An increased hematocrit can be caused by primary proliferative polycythemia (PPP), secondary polycythemia, relative polycythemia, or modifications of the red cell mass and plasma volume within their normal ranges 2.
• Smoking is the most frequent cause of an increased hematocrit, and smokers with an increased hematocrit should be asked to stop smoking before ordering blood volume studies 2.
• The presence of splenomegaly, aquagenic pruritus, and erythromelalgia often exists in PPP, whereas other symptoms such as dyspnea are more likely to be associated with secondary polycythemia 2.
• Male patients with a hematocrit over 60% and female patients with a hematocrit over 55% always have absolute polycythemia 2.
• The associations of an increased hematocrit with splenomegaly, a raised white blood cell count, or thrombocytosis are indicators for PPP, and the necessity for blood volume studies is questionable in these patients 2.
• Blood volume studies are useful in patients with an increased hematocrit and no other clinical or biological signs suggestive of any form of polycythemia 2.

Diagnostic Criteria

The diagnostic criteria for polycythemia vera (PV) have been revised, and the 2016 WHO classification decreased the threshold levels of hemoglobin and hematocrit for the diagnosis of PV 3, 4.

• The isolated use of the proposed Hb/Hct levels as a definer of polycythemia may lead to a substantial increase in unnecessary diagnostic tests 3.
• In cases with borderline levels of hemoglobin, the diagnostic workup of PV should only be indicated in the presence of clinical and/or laboratorial features associated with myeloproliferative neoplasms (MPN) 3.
• The 2016 WHO criteria significantly increased concordance between red cell mass and Hb values compared with the 2008 WHO criteria 4.
• Increased red cell mass is associated with increased Hb/Hct, and Hb/Hct threshold values may be used as surrogate markers for red cell mass measurements 4.

Interpretation of Complete Blood Cell Count

A complete blood cell count (CBC) is one of the most common laboratory tests in medicine, and it is essential to have a structured action plan when confronted with abnormal CBC results 5, 6.

• The red blood cell test components of the CBC should be evaluated, followed by a discussion of the laboratory evaluation of anemia and polycythemia 6.
• Practical diagnostic algorithms can help non-hematologists recognize when a subspecialty consultation is reasonable and when it may be circumvented, thus allowing a cost-effective and intellectually rewarding practice 5.