ORLANDO, Fla.—Correcting iron deficiency in non-dialysis CKD patients lowers platelet counts and improves erythropoiesis, researchers reported here at the National Kidney Foundation’s 2010 Spring Clinical Meetings. The result is higher hemoglobin (Hb) levels achieved with lower doses of an erythropoiesis-stimulating agent.
The investigators, led by Anatole Besarab, MD, Adjunct Professor of Medicine at Wayne State University and Director of Clinical Research at Henry Ford Hospital in Detroit, noted that iron deficiency may result in elevated platelet counts elevations that could contribute to thrombotic complications observed in clinical trials looking at the use of ESAs to correct anemia.
A previous study of more than 40,000 maintenance hemodialysis patients found that platelet counts were inversely related to the severity of iron deficiency. In addition, a post-hoc analysis of the DRIVE (The Dialysis Patients’ Response to IV Iron with Elevated Ferritin) study revealed a decrease in platelet counts following iron administration (1,000 mg over eight dialysis sessions).
In the study by Dr. Besarab and his colleagues, 132 non-dialysis CKD patients received either 500 or 1000 mg of low molecular weight iron dextran (ID) during 2-4 hour sessions to correct iron deficiency (defined as a transferrin saturation [TSAT] below 20% and ferritin level below 200). The subjects were receiving once-monthly darbepoetin injections and were on oral iron therapy (100 mg or more of elemental iron per day). The researchers measured baseline iron indices and darbepoetin use one month prior to and just before ID infusion (baseline) and one and two months after infusion. Since darbepoetin dosing is always based on laboratory values in the previous month, dose changes were permitted at baseline and one and two months after infusion.
Of the 132 patients, only 86 had complete data at all four time points. In the patients receiving 500 mg of ID, the mean Hb levels rose significantly from 10.1 and 10.0 g/dL at the first and second time points, respectively, to 10.8 and 10.9 at one and two months after ID infusion. In the 1,000-mg group, the mean Hb levels from 10.3 and 10.4 at the first and second time points to 11.7 and 11.7 at the third and fourth time points.
In the 500-mg group, mean platelet counts (per mm3) at the first and second time points were 265,000 and 280,000 and declined significantly to 235,000 and 227,000 at the third and fourth time points. In the 1,000-mg group, mean platelet counts at the first and second time points were 328,000 and 328,000 and then declined to 306,000 and 274,000 at the third and fourth time points. The average absolute decline in platelets appeared independent of iron dose.
The mean TSAT at time points one, two, three, and four were 18.7%, 12.9%, 26.8% and 26.9%, respectively, in the 500-mg group, and 15.5%, 14%, 24.5%, and 25.6% in the 1,000 mg group. Mean ferritin levels (ng/mL) at time points one, two, three, and four were 52, 37, 157, and 127 in the 500-mg group and 66, 53, 237, and 193 in the 1,000-mg group. For both of these parameters, all of the differences from baseline to one and two months post-injection were significant.
In the 500-mg group, the mean darbepoetin dose (mcg/month) decreased significantly from 166 at baseline to 137 two months after ID infusion; in the 1,000-mg group, the mean dose decreased significantly from 173 to 104 during the same period. “Iron deficiency should be vigorously treated and prevented in all clinical settings since it may potentiate thrombotic events,” Dr. Besarab said.