The activity of the von Willebrand factor cleaving protease ADAMTS-13 in newborn infants.
BACKGROUND
Unusually large von Willebrand factor (VWF) multimers have been observed in patients with thrombotic microangiopathies (TMA), and absence of the VWF cleaving protease ADAMTS-13 activity is considered to be involved in the etiology of TMA. Increased amounts of large multimers of VWF have also been identified in neonates.


OBJECTIVE
We assessed ADAMTS-13 activity in healthy neonates, children and adults to establish baseline levels.


METHODS
Cord blood was collected from 38 full-term newborns; venous samples were taken from 15 neonates on day 2-3 of life. Seventeen children, 24 healthy adults and seven patients with TMA were studied as well. ADAMTS-13 activity was quantified by the binding of the subjects' plasma VWF to collagen before and after enzyme activation. The multimer distribution of VWF was also determined.


RESULTS
Neonates and children had percentage ADAMTS-13 activity similar to adults. However, two groups were apparent in the cord blood samples: while 28/38 newborns had percentage activity within the normal range of healthy adults (102 +/- 3.0%), 10 had significantly lower percentage activity (53 +/- 1.1%; P < 0.0001) that normalized by day 2-3. The VWF multimer distribution was the same in all cord blood samples and was not different compared with children and adults. High-molecular-weight VWF multimers were significantly increased in the 2-3-day-old neonates and in TMA patients.


CONCLUSIONS
Although ADAMTS-13 activity was similar in neonates compared with adults, 26% of neonates had mildly reduced activity. Further studies are needed to investigate the complex interaction of VWF production and secretion with its size control by ADAMTS-13 in different age groups.
Hematology, University Children's Hospital, Zurich, Switzerland.
M
M
Schmugge
M S
MS
Dunn
K S
KS
Amankwah
V S
VS
Blanchette
J
J
Freedman
M L
ML
Rand
D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; D000328:Adult; D000367:Age Factors; D002648:Child; D019281:Dimerization; D005260:Female; D005312:Fetal Blood; D006463:Hemolytic-Uremic Syndrome / Q000097:blood; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008666:Metalloendopeptidases / Q000097:blood / Q000378:metabolism*; D011697:Purpura, Thrombotic Thrombocytopenic / Q000097:blood; D014680:Veins; D014841:von Willebrand Factor / Q000032:analysis / Q000378:metabolism
D014841:von Willebrand Factor; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human