Erythropoietic response to endogenous erythropoietin in premature very low birth weight infants

Abstract

Despite the common occurrence of anemia in very low birth weight (VLBW) infants, the erythropoiesis and Hb production rates and their relationship to plasma erythropoietin (EPO) concentrations remain unknown in these subjects. To determine these quantities, all blood removed by phlebotomy and administered by red blood cell (RBC) transfusion over the first 30 days of life was recorded in 14 ventilated VLBW infants born at 24 to 28 weeks of gestation. Discarded blood from frequent clinically ordered laboratory blood samples was used to construct plasma EPO, Hb, and RBC concentration-time profiles for each infant. A pharmacodynamic Hb mass balance model that accounted for the dynamic hematological conditions experienced by these infants was simultaneously fitted to the plasma EPO, Hb, and RBC concentrations from each individual subject, while accounting for subject growth. Based on the model estimates, an average of 4.69 g of Hb was produced over the first 30 days of life, compared with 5.97 g removed by phlebotomies and 12.3 g administered by transfusions. These high transfusion amounts were consistent with a relatively short RBC life span and rapidly expanding blood volume with infant growth. The estimated mean body weight-scaled Hb production rate dropped nearly 3-fold after birth to 0.144 g/day x (kg)(3/4). Although only estimated in a subset of the subjects, the mean plasma EPO EC(50) of 28.5 mU/ml and maximal Hb production rate (E(max)) indicated that a severalfold increase in Hb production rate could be achieved with only a modest increase in plasma EPO concentrations.

Fig. 1.

Mean rate of phlebotomy blood loss versus subject age.

Fig. 2.

Plasma EPO concentrations versus subject age. The solid line represents a nonparametric smoothing spline fit to the observed data (circles).

Fig. 3.

Pharmacodynamic Hb mass balance model fit to representative subjects. The symbols represent the observed data and the lines represent the model fit. A (left) and B (right) are different subjects.