Normalization of haemoglobin concentration with recombinant erythropoietin has minimal effect on blood haemostasis

Elevation of haemoglobin (Hb) with recombinant erythropoietin (rHuEpo) in patients with chronic renal failure has raised concern of increased risk of thromboembolic diseases. In this study, a substudy of the Scandinavian multicentre trial, we examined the influence on haemostatic parameters of normalization of Hb levels from subnormal levels in patients with chronic renal failure.

Twenty-six patients, 17 males (before study start Hb 113+/-6 g/l) and nine females (Hb 111+/-8 g/l), with end-stage renal disease were included. Both dialysis and predialysis patients were included. After 3 months of rHuEpo therapy Hb levels reached 136+/-14 g/l for males and 128+/-13 g/l for females, and after 1 year 142+/-11 g/l and 126+/-14 g/l respectively. The increase in Hb was significant both at 3 months and 1 year, compared to baseline. At baseline, after 3 months and 1 year haemostatic and prothrombotic parameters were measured, including prothrombin complex test, activated partial thromboplastin time, platelet aggregation and retention, von Willebrand factor antigen, antithrombin, protein C, total and free protein S, activated protein C resistance, FV-Leiden mutation, D-dimers, plasminogen activator inhibitor-1 and prothrombin fragments 1+2 (PF 1+2).

The only statistically significant change was a transient decrease in total levels of protein S at 3 months from 131 to 120% (P=0.0093). The free and active form of protein S showed no significant change. After 1 year the difference was not seen.

Apart from a transient and clinically insignificant decrease in total protein S, we found no prothrombotic changes after normalization of Hb from subnormal levels. Our findings indicate that rHuEpo treatment may aim at normalizing Hb levels without significant effects on haemostatic parameters in patients with chronic renal failure compared to patients with subnormal Hb levels.