Clarifying Different Characteristics of Erythrocytosis

JAK2-unmutated erythrocytosis has a variety of causes, and this patient population includes both patients with and without polycythemia vera (PV). A study published in the European Journal of Internal Medicine compared the characteristics of patients presenting with erythrocytosis and PV versus those without PV.

The study included adult patients with JAK2-unmutated erythrocytosis according to assays performed between 2016 and 2019. The hemoglobin thresholds for PV were 16.5 g/dL in men and 16 g/dL in women, and hematocrit thresholds were 49% and 48% in men and women, respectively. This is in line with the WHO criteria for diagnosing PV as of 2016. The hemoglobin thresholds for absolute erythrocytosis were 18.5 g/dL in men and 16.5 g/dL in women, and hematocrit thresholds were 55.5% for men and49.5% for women.

There were 1145 JAK2-unmutated patients with erythrocytosis identified at screening, the majority of whom were without a diagnosis at the time of the study. “This may reflect a lack of exploration or might question the adequation of erythrocytosis thresholds as defined by 2016 WHO to our costal population,” the authors noted.

A total of 525 JAK2-unmutated patients were included in the analysis, and 69 individuals with JAK2-mutated PV were included for comparison. The median patient age was 58 years, and 90.3% of patients were male. Arterial hypertension, venous thromboembolism, obesity, ischemic cardiopathy, diabetes, stroke, and sleep apnea were the most common comorbidities. The main clinical signs in JAK2-unmutated patients were symptoms similar to sleep apnea, headaches, general health deterioration, facial erythroses, fatigue, and pruritus.

The go-to treatment for PV in this cohort was phlebotomy. For patients at a high risk of thrombosis, cytoreductive therapy may be considered. Low-risk patients may benefit from low-dose aspirin. In non-PV patients, treatment tends to be more case-by-case, although the authors note that current research suggests a goal of symptomalleviation versus hematocritreduction.

In general, the data suggest several notable clinical and biological differences between PV and non-PV patients. Overall, non-PV patients were younger than PV patients (56 years versus 66 years) and were more often male (69.1% vs. 90.3%, P <.001). Patients with PV were more often obese (14% vs 4.9%, P =.023) and showed more of a general decline in health compared with non-PV patients (19.8% vs. 5.7%, P <.001). They were also more likely to experience facial erythroses, pruritus, splenomegaly, and erythromelalgia. 

Hematological measures also differed between the groups. Patients with PV met the threshold for absolute erythrocytosis more often than non-PV patients (54.3% vs 16.8%, P <.001). PV patients also showed higher hematocrit, white blood cell counts, neutrophilic poly-nuclear counts, and higher platelet counts compared with non-PV patients. Lymphocyte counts, eosinophilic counts, and basophilic counts were lower in PV patients than non-PV patients. Erythropoietintiters were lower in PV patients, as well.

“The distinctive features between polycythemia vera patients could lead to the establishment of a predictive score of PV for better selection of JAK2-unmutated patients with high risk of PV who are eligible for bone marrow biopsy,” the authors wrote.

A chief concern is the lack of clear diagnoses in JAK2-unmutated erythrocytosis, as well as the lack of consensus on therapy approaches. With a selection of known causes that have specific treatments, identifying the underlying cause of erythrocytosis can prove helpful in cases where it is secondary to another condition.

Reference

Ernest V, Abbou N, Tichadou A, Arcani R, Venton G. Characteristics of JAK2 unmutated erythrocytosis: Distinctive traits between polycythemia vera and non-polycythemia vera patients. Eur J Case Rep Intern Med. Published online September 10, 2022. doi:10.1016/j.ejim.2022.09.004