In Vitro Fibrinolysis After Adding Low Doses of Plasminogen Activators and Plasmin Generation with and without Oxidative Inactivation of Plasmin Inhibitors in Newborns and Adults

Ries, M.; Klinge, J.; Rauch, Ralf; Trusen, B.; Zenker, Martin; Keuper, H.; Harms, D.

doi:10.1097/00043426-199611000-00003

Cited by 26 publications

(17 citation statements)

References 36 publications

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“…[28] Reis et al used microtiter clot lysis assay for comparing in vitro fibrinolysis between newborns and adults. [29] Both studies demonstrated a more active fibrinolytic system in the neonates, and their findings are compatible with our current results. Unlike our rapid, feasible technique, those studies employed complicated laboratory tests.…”

Section: Discussionsupporting

confidence: 93%

Assessment of Functional Fibrinolysis in Cord Blood Using Modified Thromboelastography

Sidlik

Strauss

Morag

et al. 2016

Pediatr Blood Cancer

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Section: Discussionsupporting

confidence: 93%

Assessment of Functional Fibrinolysis in Cord Blood Using Modified Thromboelastography

Sidlik

Strauss

Morag

et al. 2016

Pediatr Blood Cancer

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“…One possible reason for the results of the clot lysis experiments is an alteration of the reaction kinetics between fetal plasmin and plasmin inhibitors. Direct comparison of plasmin generation with and without oxidative inactivation of plasmin inhibitors demonstrated a diminished inhibitory effect of plasmin inhibitors toward fetal plasmin, 14 which provides an explanation for the more rapid clot ly sis in newborns at low plasminogen activator concentra tions, where the inhibitors play a more potent role.…”

Section: Discussionmentioning

confidence: 99%

“…12,13 In contrast, fibrin clot lysis was faster and more efficient in new borns compared with adults at low concentrations of rt-PA and urokinase (UK). 14 suits of the clot lysis experiments is the diminished in hibitory effect of plasmin inhibitors toward fetal plasmin. 14 Although there are data on plasma clot lysis in newborns, the potential for dissolution of whole blood clots has not been explored.…”

mentioning

confidence: 99%

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Whole Blood Clot Lysis in Newborns and Adults after Adding Different Concentrations of Recombinant Tissue Plasminogen Activator (Rt-PA)

Trusen¹,

Ries²,

Zenker³

et al. 1998

Semin Thromb Hemost

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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.

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“…The same group of investigators also presented in vitro data indicating a more rapid clot lysis at low urokinase and rt-PA concentrations in newborns despite significantly reduced plasminogen levels. [69] Based on these observations it is un- Table I © Adis International Limited. All rights reserved.…”

Section: Systemic Versus Local and High Dose Versus Low Dose Thrombomentioning

confidence: 99%

Management of Preterm Infants with Intracardiac Thrombi

2001

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Improvement in neonatal care has led to improvements in survival and patient outcome in preterm infants; however, this improved survival has been associated with the development of secondary complications, such as catheter-associated intravascular and intracardiac thrombus formation with a non-negligible morbidity and mortality. The sick preterm infant is at high risk of catheter-related thrombus formation because of the combination of a high prothrombotic activity, low levels of natural anticoagulants, and various imbalances in the fibrinolytic systems. Based on clinical experience in adults and children, and several neonatal case reports demonstrating the efficacy and tolerability of specific thrombolytic treatment, this approach should be recommended as a first choice treatment in the premature infant with intracardiac or intravascular thrombosis. The thrombolytic agents of choice are urokinase or tissue plasminogen activator (tPA); however, none of them have proven to be superior to the other in terms of efficacy or tolerability, either in adult patients or premature infants. In the past, it has been suggested that newborn infants may require higher doses of thrombolytic agents than adults for effective systemic thrombolysis; however, based on more recent in vitro studies, it seems unlikely that this is true. Nevertheless, systemic (high dose) fibrinolysis is of concern as premature neonates present an increased risk of cerebral haemorrhage during the first weeks of life; therefore, low dose treatment has been proposed with, if possible, direct infusion of the fibrinolytic agent into, or close to, the thrombus. This approach has proven to be efficient and well tolerated in several small case series of newborn and preterm infants. Recommended doses are 1000 to 3000 U/kg/h for urokinase or 0.01 to 0.05 mg/kg/h for tPA. A systemic proteolytic state will not be induced by this low dose; however, specific monitoring of fibrinogen plasma levels has to be recommended. Fibrinogen levels should remain above 100 mg/dL during low dose treatment. Lower levels of fibrinogen will indicate the presence of an unwanted systemic fibrinolytic state. After successful thrombolysis, a follow-up treatment, preferentially with low-molecular-weight heparin for neonates at adjusted doses, should be instituted for at least 6 weeks in the absence of any persisting thrombophilic factor. A longer course (3 to 6 months) of anticoagulation therapy is recommended when thrombophilic factors (i.e. hereditary thrombophilia or central venous catheter still in place) are present. Furthermore, it is recommended that any neonate with thrombosis should be evaluated for hereditary thrombophilia later in life.

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In Vitro Fibrinolysis After Adding Low Doses of Plasminogen Activators and Plasmin Generation with and without Oxidative Inactivation of Plasmin Inhibitors in Newborns and Adults

Cited by 26 publications

References 36 publications

Assessment of Functional Fibrinolysis in Cord Blood Using Modified Thromboelastography

Assessment of Functional Fibrinolysis in Cord Blood Using Modified Thromboelastography

Whole Blood Clot Lysis in Newborns and Adults after Adding Different Concentrations of Recombinant Tissue Plasminogen Activator (Rt-PA)

Management of Preterm Infants with Intracardiac Thrombi

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