Published online March 2, 2009
PEDIATRICS Vol. 123 No. 3 March 2009, pp. 784-790 (doi:10.1542/peds.2007-2304)

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ARTICLE

Vascular Endothelial Growth Factor as Marker for Tissue Hypoxia and Transfusion Need in Anemic Infants: A Prospective Clinical Study

Edda Tschirch, MD^a, Benedikt Weber, MD^b, Petra Koehne, MD^c, Florian Guthmann, PhD^b, Alexander von Gise, MD^b, Roland R. Wauer, PhD^b, Mario Rüdiger, PhD^a,b

^a Department of Pediatrics IV, Neonatology, Medical University Innsbruck, Innsbruck, Austria
^b Clinic for Neonatology, Charité Universitätsmedizin Berlin, Berlin, Germany
^c Department of Neonatology and Pediatric Intensive Care, University Hospital Carl Gustav Carus Dresden, Dresden, Germany

OBJECTIVE. Oxygen-carrying capacity of blood is reduced in anemic infants because of low hemoglobin levels. Red blood cell transfusions become necessary if low hematocrit causes tissue hypoxia. No reliable parameters exist for detecting chronic tissue hypoxia. Vascular endothelial growth factor is upregulated by hypoxia; hence, elevated vascular endothelial growth factor levels may be a marker for tissue hypoxia and may indicate the need for red blood cell transfusions.

METHODS. In a prospective study, plasma vascular endothelial growth factor levels were measured in 3 groups of infants suspected of requiring red blood cell transfusions to find a vascular endothelial growth factor cutoff value indicative of tissue hypoxia. The 3 groups were acute anemic (an episode of acute bleeding [hematocrit drop > 5%] per day); chronic anemic (hematocrit drop < 5% per day); and nontransfused (hematocrit drop < 5% per day) but not meeting clinical criteria for a transfusion. Blood was sampled before transfusion and again 48 hours after transfusion if required. Plasma vascular endothelial growth factor and erythropoietin concentrations were measured.

RESULTS. Vascular endothelial growth factor concentrations were lower in acutely anemic compared with chronically anemic infants, whereas erythropoietin levels did not differ between these groups. The vascular endothelial growth factor concentration was <140 pg/mL in all acutely anemic infants, and this was deemed the threshold level indicating sufficient tissue oxygenation in subsequent analysis. We found that 30% of chronically anemic and 43% of nontransfused infants had vascular endothelial growth factor levels of >140 pg/mL. In transfused infants, with elevated vascular endothelial growth factor levels, red blood cell transfusion resulted in lowering of vascular endothelial growth factor concentrations.

CONCLUSIONS. Vascular endothelial growth factor concentrations of >140 pg/mL may indicate insufficient oxygen delivery to tissues and may serve as a marker of the need for transfusion or of tissue hypoxia in other diseases.

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Key Words: anemia of prematurity • blood • transfusion medicine

Abbreviations: BPD—bronchopulmonary dysplasia • HIF—hypoxia-inducible factor • IQR—interquartile range • RBC—red blood cell • VEGF—vascular endothelial growth factor

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Accepted Jun 16, 2008.

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