CIRCULATING MEGAKARYOCYTES AND THEIR PROGENITORS IN EARLY THROMBOCYTOPENIA IN PRETERM NEONATES

Thrombocytopenia is common in sick preterm babies. Despite this, plate let production in thrombocytopenic preterm babies has rarely been asse ssed. To address this problem we have developed miniaturized assays to study circulating megakaryocyte (MK) progenitors [burst-forming unit (BFU)-MK and colony-forming unit (CFU)-MK], total cultured MK precurso rs and mature MK, by culturing mononuclear cells purified from 0.5-1 m i of pre term peripheral blood. MK lineage colonies and cells are iden tified by an anti-IIb/IIIa antibody (CD61). We prospectively studied c irculating BFU-MK/CFU-MK, total cultured MK pre cursors and mature MK in 63 preterm babies (gestational age 24-34 wk). Twenty-six developed early thrombocytopenia (platelets <150 x 10(9)/L by 48 h), whereas the remaining 37 babies maintained normal platelet counts. Twenty-one of the 26 thrombocytopenic babies were born to mothers with pregnancy-ind uced hypertension or were growth retarded. At birth, thrombocytopenic babies had severely reduced numbers of all MK precursors compared with nonthrombocytopenic babies: BFU-MK 82 +/- 50 versus 663 +/- 174 colon ies/mL, mean +/- SEM; CFU-MK 596 +/- 196 versus 3267 +/- 530 colonies/ mL; total MK precursors 97 +/- 30 versus 301 +/- 49 x 10(3) cells/mL a nd mature MK 8 +/- 2 versus 37 +/- 8 x 10(3)cells/mL, respectively. Th rombocytopenia resolved by d 10 in all babies accompanied or preceded by a recovery to normal numbers of circulating MK progenitors. Eightee n (69%) of the thrombocytopenic babies were also neutropenic (neutroph ils <2 x 10(9)/L); in these babies neutrophil progenitor cells (CFU-gr anulocyte/monoctye) were also severely reduced compared with the nonth rombocytopenic babies (539 +/- 280 versus 1937 +/- 348 colonies/mL, me an I SEM). This indicates that the principal cause of the thrombocytop enia and neutropenia is reduced platelet and neutrophil production occ urring as a consequence of reduced numbers of MK and CFU-granuloctye/m onocyte progenitors, respectively. Taken together these data suggest t he hematologic abnormalities characteristic of newborns born to mother s with pregnancy-induced hypertension or with intrauterine growth reta rdation are a consequence of dysregulation of fetal hemopoiesis occurr ing proximal to committed MK and neutrophil progenitors, most likely a t the level of the primitive multipotent hemopoietic stem cell.