[Treatment of anaemia of prematurity with SS-R-Hu-erythropoietin and significance of hypoxia-inducible factor].
The main cause of anaemia of prematurity is low erythropoietin levels. A few years ago hypoxia-inducible factor/HIF/gene transcriptor was established, regulating not only the synthesis of erythropoietin /EPO/, but also other growth factors as well as enzymes of anaerobic glycolysis, activated by hypoxia.


OBJECTIVE
The aim of the study is to establish in clinical practice the role of hypoxia, respectively, activated HIF during treatment with erythropoietin by analyzing variations in hematological values; to examine blood lactate levels as an indicator of activated HIF and anaerobic glycolysis with Hb values 110-120 g/l; to analyze the number and impact of red blood cells transfusions on different categories of babies. STUDY DESIGN; The study includes 112 premature infants born before 34 weeks of gestation and below 1400 g. 90 babies, treated with EPO (700-1000 E/kg weekly dose in 2-3 applications, for 2-4 weeks), values of Hb g/l, Ht%, Ret%, Platelets 109/l were followed and compared. Treated babies were divided in two groups: group I--treatment (starting at Hb below 106 g/l, Ht less than 31%); group II--late prophylaxis (starting at Hb > or = 106 g/l, Ht > or = 31%). Blood lactate was examined in 22 non oxygen dependent premature babies without EPO treatment, with Hb 110-120 g/l, Ht 29-32%.


RESULTS
We found that in group II during the first 7-10 days Hb decreases to 105.6 (+/- 9.4) g/l, rising up afterwards to 113.5 (+/-11.0) g/l at day 25-30. Ret reach maximal values at day 15-20 when Hb drops below 110 g/l and Ht below 31%. In group I at day 25-30 of treatment is observed a rise in Hb up to 117.3 (+/-11.3) and of Ht up to 32.7% (+/- 2.6) and no decrease of Hb and Ht values during the first 7-10 days, while Ret rise up to maximal values 6.5% (+/- 3.6) at day 7-10. With Hb levels of 116.4 (+/- 4.6) g/l we found an increase in blood lactate levels up to 2.6 (+/- 0.7) mmol/l as an indicator of relative hypoxia and activated HIF. Mean number of blood transfusions in group I is 3.01(+/- 1.7), versus 2.15 (+/- 1.7) in group II (statistically non-significant). In 29 infants in group II treatment was started at Hb 110-120 g/l and the mean number of red blood cell transfusion is 1.8 (1.5)--statistically significant difference with group I. In 32% from the treated infants we found platelets count rising above 500 x 109/l.


CONCLUSIONS
The presence of hypoxia at low levels of Hb and Ht leads to more rapid activation of erythropoiesis. Nevertheless, these babies need more red blood cell transfusions due to clinical symptoms of hypoxia. Normoxia after red blood cell transfusion leads to decrease of reticulocytes count by 30% and platelets by 35% in spite of treatment. The presence of relative hypoxia with Hb 110-120 g/l u Ht 31-32% is optimal for starting treatment with EPO--levels, low enough for activation of HIF and high enough to avoid blood transfusions.
Pramatarova
T
T
Sluncheva
B
B
Jarukova
N
N
Vakrilova
L
L
Emilova
Z
Z
Shishkova
R
R
Dimitrov
A
A
Nikolov
A
A
Radulova
P
P
Chitrova
S
S
D000751:Anemia, Neonatal / Q000188:drug therapy* / Q000628:therapy; D017707:Erythrocyte Transfusion; D004921:Erythropoietin / Q000627:therapeutic use*; D006400:Hematocrit; D006452:Hemoglobinometry; D006801:Humans; D000860:Hypoxia / Q000097:blood*; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D007231:Infant, Newborn; D007234:Infant, Premature / Q000097:blood*; D019344:Lactic Acid / Q000097:blood; D011994:Recombinant Proteins
D051793:Hypoxia-Inducible Factor 1; D011994:Recombinant Proteins; D004921:Erythropoietin; D019344:Lactic Acid