Evaluating the Incidence of Cardiovascular and Thrombotic Events in Secondary Polycythemia

Introduction: Secondary polycythemia is a disorder of increased hemoglobin or hematocrit most often resulting from states of systemic hypoxia such as chronic obstructive pulmonary disease (COPD). Many patients with secondary polycythemia are treated with phlebotomy to reduce hematocrit levels based on recommendations for polycythemia vera (PV)-a myeloproliferative neoplasm characterized by increased red blood cell mass and a greater risk for thromboembolic events-despite the lack of evidence demonstrating whether or not secondary polycythemia patients share this increased risk. While the pro-thrombotic state in PV has been associated with JAK2 allele burden, leukocytosis, and hypercoagulability, similar changes have not been reflected in secondary polycythemia. Because there is limited data on the efficacy or necessity of phlebotomy in patients with secondary polycythemia, our study aims to determine if phlebotomy affects the prevalence of arterial and venous thrombotic events in this patient population

Methods: We retrospectively identified patients seen at Rhode Island Hospital/The Miriam Hospital from 1/1/2000 to 1/1/2019 with COPD and a diagnosis of secondary polycythemia via ICD9 coding. Polycythemia was defined as a hemoglobin level greater than 16.0 g/dL in women or 16.5 g/dL in men on at least 2 separate occasions. Data was collected on JAK2 allele status, phlebotomy treatment, co-morbidities, hematologic values, and thrombotic events. Arterial thrombotic events included myocardial infarction (MI), cerebrovascular accident (CVA), and transient ischemic attack (TIA). Venous thrombotic events included deep vein thrombosis (DVT) and pulmonary embolism (PE). Analysis of data was done by chi-square and Mann-Whitney U testing.

Results: We identified 151 COPD patients who had a median age of 58 years and hemoglobin of 17 g/dL at time of secondary polycythemia diagnosis. Of these patients, all 58 (38.4%) that underwent testing were negative for the JAK2 V617F allele. Within the study population, 35 (23.2%) of patients were treated with phlebotomy and 116 (76.8%) were not. There was no difference in the median time of follow up for those who did and did not receive phlebotomy (5.6 vs 4.3 years, p=0.46). Phlebotomized patients had a higher hemoglobin (17.1 g/dL vs 16.9 g/dL, p=0.02) and hematocrit (52.2% vs 50%, p=0.007) compared to non-phlebotomized patients. Patients who underwent phlebotomy were more likely to be older (p=0.1) and have obstructive sleep apnea (p=0.06) (Table 1). Thrombotic events were recorded in 22.4% (26/116) of non-phlebotomized patients and 31.4% (11/35) of phlebotomized patients, with no statistically significant difference between the two groups (p=0.28) (Figure 1). Of the 42 patients who had COPD further confirmed by pulmonary function testing (PFT) with a documented post-bronchodilator FEV₁/FVC < 0.7, there was also no significant difference in prevalence of total thrombotic events between patients who were and were not treated by phlebotomy. In this group of patients, there were thrombotic events in 18.8% (6/32) of phlebotomized patients and 10% (1/10) of non-phlebotomized patients (p=0.66). There was no statistically significant difference in prevalence of thrombotic events in phlebotomized patients who did and did not achieve phlebotomy goals. Patients who achieved a goal of hematocrit < 52% had a 25% (4/16) prevalence of thromboses compared to 36.8% (7/19) in those who did not (p=0.45).

Conclusions: We found no difference between prevalence of arterial, venous, or total thromboses in COPD patients with secondary polycythemia who were phlebotomized compared to those who were not. Similarly, there was no statistically significant reduction in prevalence of thrombotic events in patients who met the phlebotomy hematocrit goal of 52%. Thus, while secondary polycythemia patients often undergo phlebotomy to reduce hematocrit levels, our results provide no clear evidence that phlebotomy is necessary for or effective at reducing thrombotic risk in secondary polycythemia patients.

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