High Availability of Intravascular Tissue Factor in Neonates

Abstract

In the present study, we compared the levels of intravascular tissue factor (TF) present in cord versus adult whole blood (WB) prior and after lipopolysaccharide (LPS) stimulation. High levels of intravascular TF might help to explain the clinically observed efficient clotting of cord blood despite low levels of procoagulatory factors. Quantitative reverse transcription-polymerase chain reaction revealed same (basal) TF mRNA expression levels in both native cord and adult WB, and approximately same increase in TF mRNA expression owing to LPS incubation in both cord and adult WB (normalized to the housekeeping gene beta-actin). Flow-cytometric (fluorescence activated cell sorting) analysis revealed significantly higher surface TF antigen exposure on the neonatal monocyte membrane in native WB samples, and approximately same ability of neonatal and adult monocytes to express TF upon LPS-stimulation. Thrombelastography revealed significantly shorter clotting times of native cord versus adult WB (527+/-41 vs. 592+/-23 s, P<0.05). Moreover, shortening of clotting times owing to LPS-stimulation was significantly more pronounced in cord versus adult WB (29.65+/-3.35% vs. 12.03+/-6.23%, P<0.05). Because both quantitative reverse transcription-polymerase chain reaction and fluorescence activated cell sorting analysis revealed same capability of both neonatal and adult monocytes to express TF upon LPS-stimulation, this efficient shortening effect in cord WB might be explained by the constitutively high number of monocytes present in neonates. We suggest that the high levels of intravascular TF present in neonates (prior and after LPS-stimulation) might help to explain the clinically observed efficient clotting of cord blood despite low levels of procoagulatory factors.

Clot formation of neonates tested by thromboelastography correlates with gestational age

“…A finding of specific interest was the inverse correlation shown between CT and GA. Low anticoagulant action of activated protein C, antithrombin and tissue factor pathway inhibitor in cord plasma (1)(2)(3)(4), that may explain the good haemostasis observed in neonates despite low levels of procoagulant clotting proteins, may also account for faster clot formation due to delayed clot formation inhibition in neonates. Faster clot formation, as manifested by shorter CT, is indeed supported by our data as well as by previously mentioned reports (25,26).…”

“…This finding may account for poorer clot strength in premature infants, as noted by us. Kattner et al (25) in a smaller study, using TEG, showed similar MA as compared to adults in infants hospitalised in neonatal intensive care already pre-treated with vitamin K and blood products; thus, their results are not in contrast with our baseline cord blood findings. In the same study decreased R (comparable to our shorter CT/CFT) was reported as well.…”

The role of carrier number on the procoagulant activity of tissue factor in blood and plasma

“…In vivo [16] and in vitro [17], circulating TF has been shown to be active in initiating coagulation and indeed contribute to experimental thrombosis at sites of vessel injury [18,19]. However, healthy subjects have been shown to have a basal level of circulating TF without evidence for pathological initiation of coagulation [17,20]. Conversely, induction of TF-bearing microparticles restored hemostasis in a mouse model of hemophilia [21].…”

Clot Strength: A Comparison Between Cord and Adult Blood by Means of Thrombelastometry

“…[1][2][3] Both platelet count and fibrinogen concentration are similar in newborns and adults. [4][5][6] However, various studies have shown an in vitro hypofunctional state of neonatal platelets 7-9 and a delayed aggregation rate of cord versus adult fibrin. 10,11 Thus, an impaired quality of a clot formed in cord whole blood (WB) compared with a clot formed in adult WB has to be expected.…”