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SummaryPrevious studies investigating continuous unfractionated heparin (UFH) therapy report age-related differences in UFH response in children, as measured by APTT and anti-Xa assay. This study determined the age-related response following administration of a single UFH bolus of 75–100 IU/kg in children. Venous blood samples were collected from children (n=56) at 15, 30, 45 and 120 minutes post-UFH. Anti-Xa, anti-IIa, APTT, TCT and protamine titration were performed on all samples. Age-dependent differences in the effect and concentration of UFH were identified for the anti-Xa, anti-IIa and protamine titration as-says, respectively. In addition, a trend suggesting a proportional increase in anti-Xa and anti-IIa-mediated UFH effect with age was evident. Logistic regression demonstrated an increase in protamine titration of 0.6 IU/ml for every year of age in samples collected 15 minutes post-UFH. UFH-mediated anti-IIa activity was reduced compared to anti-Xa activity across childhood, with a two-fold increase in anti-Xa to anti-IIa ratio in infants less than one year of age compared to teenagers in the setting of high UFH concentrations. This study demonstrates that the previously reported age-dependent response to UFH occurs in the context of an age-dependent serum concentration of UFH. The trend toward increased UFH serum concentration and anticoagulant activity with age may be related to short-term differences in UFH binding to coagulant and competitive plasma proteins in vivo.

SummaryProtein S, protein C and antithrombin are important regulators of coagulation. While deficiencies of these proteins have been linked to adverse pregnancy outcomes, testing for these deficiencies during pregnancy is limited by the use of non-pregnant reference ranges and a limited understanding of the changes that occur during pregnancy. Although several small studies have previously reported on the activity of these proteins during pregnancy, potentially important changes have been overlooked by continuing to compare the activity during pregnancy with non-pregnant reference ranges. In the current study, we investigated the activity of protein S, protein C and antithrombin during the first half of pregnancy in 440 otherwise asymptomatic women who went on to have uncomplicated singleton pregnancies. Consistent with previous studies, we found that antithrombin activity remained unchanged, while protein S activity decreased significantly to a mean level of 46%. We did not observe a progressive decrease in protein S during the second trimester as several studies have suggested previously. In contrast, we observed a potentially biologically significant increase in protein C activity throughout the first 22 weeks of pregnancy. Given the physiological role of protein C, we postulate that this increase may play a role in maintaining early pregnancy through both an anticoagulant and an inflammatory regulation pathway.