CO-Rebreathing in Comparison to Isotopic Red Cell Volume Determination in the Diagnosis of Primitive and Secondary Polycythemia

The definition of a true polycythemia is stricto sensu an increased red cell mass (RCM) above 125% of the expected value depending on the size and the weight of the patient. However, this measurement requires an isotopic labeling of red cells and is not available in most of the hospitals. Therefore, the diagnosis of polycythemia, and particularly Polycythemia Vera (PV) is based on routine red blood cells parameters, i.e. hemoglobin level and hematocrit. If these parameters are efficient in marked polycythemia, discrepancies have been observed in milder cases. Two situations where a RCM evaluation is particularly required can be described:

• In patients with a hematocrit level between 52 and 60% (men) or between 48 and 56% (women) in order to limit invasive investigations to patients with a confirmed polycythemia diagnosis
• In JAK2V617F positive myeloproliferative neoplasms (MPN) with hematocrit and hemoglobin levels under the PV cut-off in order to discriminate between masked PV and essential thrombocythemia CO-Rebreathing is a fast, non invasive alternative method for RCM evaluation. It is based on the high affinity of carbon monoxide (CO) for hemoglobin. The decrease in the HbCO percentage after CO inhalation is dependent on the total hemoglobin mass from which RCM can be obtained. The investigators propose a tri-centric study evaluating CO-Rebreathing as an alternative tool to measure RCM in the diagnosis of polycythemia in the two categories of patients described above.

Inclusion criteria

• Adult patient
• Informed consent obtained
• Requirement of an isotopic red cell mass determination:

a - Hematocrit between 52 and 60% (men) or 48 and 56% (women) with no argument for a PV (JAK2V617F negative, EPO level normal/high).

b - Patients with a JAK2V617F positive MPN and a hematocrit level between 46 and 50% (women) or 48 and 52% for men.

• No recent vascular event (<6 mois)
• No unstable coronaropathy
• Non smoking since 24 hours.
• ECOG <2
• Negativity of pregnancy test/effective contraception for childbearing age women,
• Health insurance

Exclusion criteria

• Recent venous event <1 months, cerebral stroke < 6 mois)
• Evolutive cardiopathy (< 6 months)
• Chronic Respiratory failure
• Smokers with no withdrawal in the last 24 hours before CO-Rebreathing
• Basal HbCO>7% the day of CO-Rebreathing
• Pregnant or breast feeding women
• Patient enable to give an informed consent
• Inclusion in an interventional clinical trial in the last three months.
• Any contraindication to lung function testing