alpha 2-Macroglobulin remains as important as antithrombin III for thrombin regulation in cord plasma in the presence of endothelial cell surfaces.
Infants and children rarely develop thrombotic complications compared with adults, suggesting that there are protective mechanisms in place for the young. Because endothelial cell surfaces regulate thrombin formation and inhibition, we compared thrombin regulation by human umbilical vein endothelial cell surfaces exposed to defibrinated cord and adult plasmas. After activation by either 10% activated partial thromboplastin reagent (strong activator) or coagulant phospholipids (weak activator) the following were measured: free thrombin, thrombin bound to antithrombin III (ATIII), heparin cofactor II, alpha 2-macroglobulin (alpha 2M), and prothrombin concentration. Free thrombin activity was expressed as remaining activity, after subtraction of thrombin-alpha 2M activity. After 10% activated partial thromboplastin reagent, 100% of prothrombin was consumed and significant amounts of thrombin generated by 2 min. Cord plasma generated significantly less thrombin than adult plasma, reflecting the lower initial plasma concentration of prothrombin. correspondingly, concentrations of thrombin inhibitor complexes were significantly greater in adult plasma than in cord plasma. After coagulant phospholipids, 50% of prothrombin was consumed and negligible thrombin activity measured for both adult and cord plasma. Similar amounts of thrombin inhibitor complexes were formed. ATIII was the predominant inhibitor of thrombin in adult plasma, whereas alpha 2M was as important as ATIII in cord plasma for both activators. When cord plasma concentrations of ATIII were increased to adult values, the proportion complexed to alpha 2M decreased. We conclude that on human umbilical vein endothelial cells, the capacity to generate thrombin is decreased in adult and cord plasmas.(ABSTRACT TRUNCATED AT 250 WORDS)
Ling
X
X
Division of Hematology, St. Joseph's Hospital, London, Ontario, Canada.
Delorme
M
M
Berry
L
L
Ofosu
F
F
Mitchell
L
L
Paes
B
B
Andrew
M
M
D000328:Adult; D000375:Aging / Q000097:blood; D000595:Amino Acid Sequence; D000990:Antithrombin III / Q000502:physiology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D005312:Fetal Blood / Q000502:physiology*; D005326:Fetal Proteins / Q000096:biosynthesis*; D006801:Humans; D007223:Infant; D008969:Molecular Sequence Data; D010314:Partial Thromboplastin Time; D010743:Phospholipids / Q000502:physiology; D010969:Plastics; D011516:Prothrombin / Q000378:metabolism; D013499:Surface Properties; D013917:Thrombin / Q000096:biosynthesis / Q000502:physiology*; D000511:alpha-Macroglobulins / Q000502:physiology*
D005326:Fetal Proteins; D010743:Phospholipids; D010969:Plastics; D000511:alpha-Macroglobulins; D000990:Antithrombin III; D011516:Prothrombin; D013917:Thrombin