Posttransplant erythrocytosis and the risk of thromboembolic complications: Correlation from a prospective randomized study of cyclosporine versus azathioprine‐antilymphocyte globulin

To determine whether renal allograft recipients with sustained or transient elevation in hemoglobin (Hgb) level are at increased risk for thromboembolism, we examined the incidence of arterial and venous thromboembolic events in various subgroups of 224 patients who were prospectively randomized and stratified by risk to treatment with either cyclosporine‐prednisone (CSA‐P) (n = 117) or azathioprine‐prednisone‐antilymphocyte globulin (AZA‐P‐ALG) (n = 107). Eleven CSA patients (9.4%) and 4 AZA patients (3.7%) developed posttransplant erythrocytosis (PTE) (p = 0.08). There were no significant differences in the incidence of thromboembolic events among subgroups of phlebotomized or nonphlebotomized, CSA‐ or AZA‐treated, PTE patients, nor did these incidence rates differ significantly from those for the entire AZA and CSA groups. There was no significant increase in the incidence of thromboembolism in any of the CSA‐treated subgroups with “sustained” (≥ 1 year) or transient elevation in Hgb level when compared with the CSA‐P group as a whole or with CSA subgroups with lower Hgb levels. The percentage of AZA‐treated patients with thromboses increased in parallel with sustained Hgb levels, reaching statistical significance when patients with Hgb ≥ 16 g/dl for at least 1 yr were compared to the AZA‐P‐ALG group as a whole (p = 0.02), to AZA subgroups with lower Hgb levels (Hgb ≥ 14 g/dl for at least 1 yr, Hgb never > 17 g/dl, and Hgb never > 14 g/dl; p = 0.02, 0.02, and 0.05, respectively), and to their CSA‐treated counterparts (p = 0.03). Under both immunosuppressive regimens, however, Hgb levels tended to be low precisely at the time when patients in all subgroups had their complications. We conclude that neither transient marked elevations nor modest sustained elevations of Hgb level per se is directly associated with an increased incidence of thromboembolic complications in renal transplant recipients. PTE can be successfully managed without an increase in thromboses if therapeutic phlebotomy is utilized to maintain the hematocrit (HCT) < 50–55% and/or to treat symptoms attributable to polycythemia.