ENDOGENOUS THROMBOPOIETIN LEVELS AND EFFECT OF RECOMBINANT HUMAN THROMBOPOIETIN ON MEGAKARYOCYTE PRECURSORS IN TERM AND PRETERM BABIES

Thrombocytopenia (platelets <150 x 10(9)/L) is common in the early new born period. Recent evidence suggests this is due mainly to impaired f etal megakaryocytopoiesis/platelet production. The cause remains unkno wn. Thrombopoietin (Tpo) is now recognized as the major regulator of p latelet production in adults. However, nothing is known about Tpo leve ls, or the role of Tpo in megakaryocytopoiesis/platelet production, in the fetus/newborn. To answer these questions we: 1) measured plasma T po levels by ELISA at birth in healthy term (n = 17) and preterm (gest ational age, 24-34 wk) babies (n = 16), and in thrombocytopenic preter m babies (n = 13); and 2) assessed the in vitro Tpo dose response char acteristics of circulating megakaryocyte precursor cells (MKp) from al l three groups. The median Tpo levels were similar in term babies 145 pg/mL (range 52-237 pg/mL) compared with preterm babies 132 pg/mL (32- 318 pg/mL). Ln the thrombocytopenic preterm babies the median Tpo leve l of 185 (46-264) was not significantly higher than in healthy babies, despite the fact that their median platelet counts were significantly lower-82 x 10(9)/L (range 21-135), compared with the healthy preterm babies 252 x 10(9)/L (152-320)-p < 0.0001. Tpo levels in the thrombocy topenic preterm babies were also much lower than levels measured in th ree thrombocytopenic children (905, 2138, and 2700 pg/mL). MKp from al l three groups showed dose-dependent proliferation in response to Tpo (p < 0.01 at 100 ng/mL Tpo). Increases in MKp were greater in healthy and thrombocytopenic preterm babies when compared with term babies: 48 .2-, 24.6-, and 9.8 fold, respectively (p < 0.05 for both comparisons) . These results strongly suggest that: 1) Tpo is a major regulator of megakaryocytopoiesis/platelet production in the fetus/newborn, 2) impa ired fetal Tpo production may be a factor in early thrombocytopenia in preterm babies, and 3) recombinant human Tpo is Likely to be effectiv e in the treatment of early neonatal thrombocytopenia.