Monitoring unfractionated heparin in children: a parallel-cohort randomized controlled trial comparing 2 dose protocols.

Monitoring unfractionated heparin (UFH) is crucial to prevent over- or under-anticoagulation. However, the optimal parameters for monitoring UFH in children are not well established. The study objectives were to investigate (1) the relationship between UFH dose and its anticoagulant effect as assessed by anti-Xa, activated partial thromboplastin time (aPTT) and activated clotting time (ACT); (2) other factors influencing UFH effect; (3) the agreement between the assays; and (4) the association between UFH effect and clinical outcome. HEARTCAT was a parallel-cohort randomized controlled trial comparing high-dose (100 U/kg bolus followed by age-based continuous infusion in randomized children) vs low-dose UFH (50 U/kg bolus) during cardiac catheterization in children. Blood samples were drawn before and after UFH administration at 30, 60, and 90 minutes. Four-hundred and two samples of 149 patients were evaluable. Anti-Xa, aPTT, and ACT all showed good discrimination between UFH doses. Regression models demonstrated the following determinants of UFH effect: UFH dose, age, baseline antithrombin (for anti-Xa), and baseline levels of aPTT and ACT, respectively. UFH effects were lower in infants compared with older children, which was more pronounced at low-dose than at high-dose UFH. Agreement between the 3 assays was poor. Most aPTT values were above therapeutic range or beyond measuring limit and thus of limited value for UFH monitoring. No association of UFH dose or effect with clinical outcome could be observed. In conclusion, all assays reflected a significant UFH dose-effect relationship, however, with poor agreement between the respective tests. The age-dependency of UFH effect was confirmed. Notably, the influence of age on UFH effect was dose-dependent.

Reptilase time (RT).

The reptilase time is a functional plasma clotting assay, which is based on the enzymatic activity of batroxobin. By specifically cleaving fibrinogen A from fibrinogen, batroxobin leads to the formation of a stable fibrin clot. The time, starting from the addition of batroxobin to the plasma sample, until clot formation is the reptilase time and is given in seconds. Clot formation can be detected manually or on automated coagulation systems. Reference values for healthy adults are 18-22 s. Healthy newborns may have a slightly prolonged reptilase time of up to 24 s. In addition to other coagulation assays, the reptilase time is usually performed to confirm or to exclude the suspicion of dysfibrinogenemias. The reptilase time is independent of thrombin generation disturbances or disturbances in the action of thrombin on fibrinogen. Therefore, it can be used to confirm heparin contamination or to obtain similar information as with the thrombin clotting time in heparinized and hemophiliac patients.