Thrombopoietin levels in cord blood plasma and amniotic fluid in fetuses with alloimmune thrombocytopenia and healthy controls

Abstract

Summary. To extend our knowledge of the kinetics of fetal thrombopoietin (TPO), we studied TPO levels in cord blood plasma and amniotic fluid collected from 15 fetuses considered to be at risk of fetomaternal alloimmune thrombocytopenia and also from 10 healthy controls at caesarean delivery. In the plasma of all 25 fetuses and newborn infants studied, TPO was detected above the lower limit of detection (7 pg/ml) and correlated inversely with platelet counts (r 20´53, P 0´006). At term, TPO detected in amniotic fluid was at significantly lower levels (7 pg/ml; range 0±22 pg/ml) than simultaneously obtained cord plasma TPO (114 pg/ml; range 43±201 pg/ml; P , 0´001). There was no correlation between levels of TPO in amniotic fluid and cord plasma or platelet counts. In the serial samples collected from the five fetuses with HPA1a alloimmunization before 37 weeks' gestation, the TPO levels in amniotic fluid were significantly higher than at term (P 0´013): from 22 to 28 weeks' gestation, 42 pg/ ml (30±78 pg/ml); from 32 weeks', 24 pg/ml (17±33 pg/ ml); at term, 8 pg/ml (4±13 pg/ml), correlating inversely with gestational age (r 20´81, P 0´003). Thus, TPO is present in amniotic fluid at levels apparently inversely related to gestational age. Whether these high levels seen early in pregnancy are normal or are associated with the HPA-1 alloimmunization remains to be shown.Keywords: thrombopoietin, fetal, cord blood, amniotic fluid, alloimmune thrombocytopenia.Thrombopoietin (TPO), discovered only 5 years ago, is the primary regulator of megakaryopoiesis and thrombopoiesis (Kaushansky, 1998). The TPO molecule is a 60-to 70-kDa 332-amino-acid glycosylated polypeptide displaying homology to erythropoietin (EPO), the primary regulator of red blood cell production. In adults, TPO is produced principally in the liver, and circulating TPO levels are regulated by TPO receptors on platelets and megakaryocytes. Thus, circulating TPO levels are inversely correlated with platelet and/or megakaryocyte mass (Chang et

Longitudinal thrombopoietin plasma concentrations in fetuses with alloimmune thrombocytopenia treated with intrauterine PLT transfusions

“…Our study reveals that the median TPO concentration in severe FMAIT is significantly elevated which is consistent with data from Sainio et al 17 as determined in a lower number of patients. In contrast, Porcelijn and coworkers 20 could not detect differences in TPO concentrations between fetuses with FMAIT and healthy neonates or nonthrombocytopenic fetuses with HDN.…”

“…‐26 It is an inherent problem to gain a considerable high number of normal fetal blood samples for determining reference values. Previously, fetal TPO concentrations were compared with those measured in cord blood taken at birth in preterm and term neonates or adults 17,20 , 24,25 . In this study, fetal TPO plasma concentrations are described in fetuses with normal hematopoiesis, where perinatal effects on TPO concentrations can be excluded, as mentioned by others 27 .…”

“…Four previous studies focused on the biology of TPO in FMAIT. Sainio and colleagues 17 reported on higher TPO plasma concentrations before intrauterine PLT transfusions in five thrombocytopenic fetuses with FMAIT (PLT count, 20‐174 × 10 9 /L) owing to antibodies to HLA‐1a in comparison to controls (cord blood samples taken at birth). However, in 80 percent of the samples, TPO concentrations were in the normal range.…”

Megakaryocyte Growth and Development Factor Is a Potent Growth Factor for Primitive Hematopoietic Progenitors in the Human Fetus

“…MGDF mRNA has also been detected in the fetal and adult bone marrow as well as in organs such as kidney and spleen. The levels of MGDF in plasma are higher in the fetus and neonate than in the adult (17,19,20). The presence of MGDF in fetal hematopoietic tissues, such as the liver and bone marrow, indicates that this cytokine is a likely physiologic regulator of fetal hematopoiesis.…”

Developmental biology of thrombopoietin in the human fetus and neonate

“…For instance, it would be important to analyze corresponding data on megakaryopoietic activity when the sample is obtained. Current data on fetal Tpo concentrations are limited and obtained from fetuses who underwent cordocentesis because of Rhesus (Rh) alloimmunization, fetal alloimmune thrombocytopenia (FAITP) or prenatal diagnosis of genetic disorders (111,117,118). Sainio et al found similar Tpo concentrations in non-thrombocytopenic fetuses (n = 7; 36-37 wk of gestation) with fetomaternal incompatibility of human platelet antigens as in controls at birth.…”