Higher concentrations of heparin and hirudin are required to inhibit thrombin generation in tissue factor-activated cord plasma than in adult plasma.
Neonatal plasma clots slower than adult plasma, and only 30-50% of peak adult thrombin activity can be produced in neonatal plasma when high amounts of tissue factor (TF) are added to trigger clotting, as used in standard clotting assays. Plasma activation by addition of low amounts of TF probably better reflects conditions in vivo. Under these conditions, cord plasma clots faster than adult plasma. In the present study, we show that after activation with low amounts of TF, higher amounts of the anticoagulants heparin and hirudin are required in cord plasma for effective inhibition of thrombin generation compared with adult plasma. After strong activation with high amounts of TF (30 microM), the thrombin potential was significantly more suppressed in cord plasma compared with adult plasma in the presence of 0.4 IE/mL heparin (-92 versus -75%; p < 0.01) and in the presence of 2 IE/mL hirudin (-18 versus -8%; p < 0.01). In contrast, after weak activation with low amounts of TF (30 pM), the thrombin potential was significantly more suppressed in adult plasma compared with neonatal plasma in the presence of 0.025 IE/mL heparin (-93 versus -8%; p < 0.01) and in the presence of 2 IE/mL hirudin (-89 versus -48%; p < 0.01). Our results show that in neonates, effects of anticoagulants very much depend on the type of activation used to initiate clotting, and doses of anticoagulants should not be derived from studies done in adults, because potentially higher doses of anticoagulants may be required.
Baier
Katrin
K
Ludwig Boltzmann Researrch Institute for Pediatric Hemostasis and Thrombosis, Medical University of Graz, Graz, Australia.
Cvirn
Gerhard
G
Fritsch
Peter
P
Köstenberger
Martin
M
Gallistl
Siegfried
S
Leschnik
Bettina
B
Muntean
Wolfgang
W
D000328:Adult; D000367:Age Factors; D000925:Anticoagulants / Q000494:pharmacology; D000991:Antithrombins / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D004305:Dose-Response Relationship, Drug; D005312:Fetal Blood / Q000378:metabolism*; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology*; D006629:Hirudins / Q000494:pharmacology*; D006801:Humans; D007231:Infant, Newborn; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism*
D000925:Anticoagulants; D000991:Antithrombins; D005343:Fibrinolytic Agents; D006629:Hirudins; D006493:Heparin; D013925:Thromboplastin; D013917:Thrombin