Whole blood clot lysis in newborns and adults after adding different concentrations of recombinant tissue plasminogen activator (Rt-PA)
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1Klinik mit Poliklinik für Kinder und Jugendliche, Universität Erlangen-Nürnberg, Erlangen, Germany.
Insights
Newborns show more efficient whole blood clot lysis than adults. This suggests lower recombinant tissue plasminogen activator (rt-PA) dosages may be needed for neonatal thrombolytic therapy.
Area of Science:
- Neonatal Medicine
- Hematology
- Pharmacology
Background:
- Thromboembolic complications in newborns require tailored treatments due to developmental differences in coagulation and fibrinolysis compared to adults.
- Existing research on neonatal clot lysis primarily focuses on plasma clots, leaving whole blood clot dissolution unexplored.
- Understanding neonatal whole blood clot lysis is crucial for developing effective antithrombotic therapies.
Purpose of the Study:
- To investigate and compare the sensitivity of whole blood clots to lysis by recombinant tissue plasminogen activator (rt-PA) in newborns versus adults.
- To determine optimal rt-PA concentrations for neonatal whole blood clot lysis.
- To inform the development of specific guidelines for thrombolytic therapy in neonates.
Main Methods:
- Whole blood clots were generated from 15 newborns and 13 adults using thrombin and calcium after anticoagulation with sodium citrate.
- Clots were incubated in autologous plasma and exposed to varying concentrations of rt-PA (0–3 μg/mL).
- Clot weight was measured over time (0.5, 1, 2, and 3 hours) to assess lysis efficiency.
Main Results:
- Whole blood clots from newborns demonstrated significantly more efficient spontaneous lysis and rt-PA-induced lysis compared to adult clots at all measured time points.
- Optimal lysis in newborns occurred at 1 μg/mL rt-PA, while adults required the highest concentration tested (3 μg/mL) for maximal lysis.
- Plasminogen consumption rates were comparable between newborns and adults, despite differences in fetal plasminogen levels and activation kinetics.
Conclusions:
- Neonatal whole blood clots are more susceptible to lysis than adult clots, indicating distinct responses to thrombolytic agents.
- The findings suggest that current antithrombotic therapy recommendations for newborns, often extrapolated from adults, may not be optimal.
- A lower dosage of rt-PA is likely appropriate for thrombolytic therapy in newborns compared to adults, necessitating further clinical guideline development.
Abstract:
Optimal treatment of newborns with thromboembolic complications likely differs from that for adults because of ontogenetic features of both coagulation and fibrinolysis that affect the thrombotic processes and the response to thrombolytic agents. Although there are data on plasma clot lysis in newborns, the potential for dissolution of whole blood clots has not been explored. We investigated whether there is a difference between newborns and adults in sensitivity of whole blood clots to lysis with recombinant tissue plasminogen activator (rt-PA). Blood was obtained from 15 newborns and from 13 adults and anticoagulated with sodium citrate. Whole blood clots were generated by addition of thrombin and calcium. After 3 hours of retraction the clots were put into tubes containing 1.45 mL plasma of the same patient. After 1 hour of incubation, rt-PA was added to result in final concentrations of 3, 1, 0.3, 0.1, and 0 microg/mL. Clots were weighed after 0.5, 1, 2, and 3 hours. At any time point measured, whole blood clot lysis was more efficient in newborns than it was in adults. This was true for spontaneous clot lysis (p <0.05 at 1, 2, and 3 hours) as well as for all concentrations of rt-PA tested (p <0.05 at 1 hour). Whole blood clot lysis in new-borns was most efficient at 1 microg/mL rt-PA, whereas adults showed best lysis at the highest concentration tested (3 microg/mL rt-PA). The rate of plasminogen consumption was similar in newborns and adults. Recommendations for antithrombotic therapy in new-borns have been loosely extrapolated from recommendations for adults. Our data can be helpful in establishing guidelines for thrombolytic therapy in the neonatal period. Retracted whole blood clots mimic better the in vivo situation than previously reported in studies of lysis of nonretracted plasma clots. Based on our data, we think that despite low levels and slower activation kinetics of fetal plasminogen, the dosage of rt-PA should be lower in newborns than in adults.
