Thrombolysis in children

Abstract

Summary Thrombosis in children may result in vascular occlusion and a potential loss of viability in skin, limbs or organs, or lead to the development of post thrombotic syndrome. Thrombolysis may prevent such complications, and the use of thrombolytics in children has increased in the last three decades. Despite this, optimum paediatric treatment regimens for these drugs remain uncertain, and accurate efficacy and safety profiles for thrombolytics are limited by the lack of controlled, prospective studies in well‐defined patient populations. Restoration of vessel patency has often been achieved but the risk of intracranial and other major haemorrhage secondary to thrombolysis continues to be a significant concern for the clinician deciding on such treatment. This review summarises the use of thrombolytic treatment in children and describes outcome data and adverse events following treatment, as well as the limitations of published studies on paediatric thrombolysis.

Neonatal haemostasis and the management of neonatal thrombosis

“…It is clear from the more recent literature that with increasing experience in the use of rTPA, these contraindications are no longer considered to be absolute. Recombinant tissue plasminogen activator is most often administered systemically but it can by also be locally infused directly into the affected blood vessel (Manco-Johnson, 2006;Williams, 2009). rTPA is also very effective when instilled at low dose to unblock central lines.…”

“…Thrombolysis. Recombinant tissue plasminogen activator has superseded both streptokinase (SK) and urokinase (UK), though recombinant urokinase (rUK) is under clinical assessment (Williams, 2009). rTPA is a very powerful thrombolytic but its potential to cause haemorrhage limits its use to neonates with extensive thrombosis or thrombosis that places life, organ function or a limb in danger (Williams et al, 2002;Greenway et al, 2004;Monagle et al, 2012).…”

“…On day one of life, the term neonate has plasminogen levels that are approximately 60% of the normal adult range, tissue plasminogen activator (TPA) is over twice that of a normal adult, a 2 -antiplasmin (a 2 AP) is moderately reduced and plasminogen activator inhibitor (PAI) is almost double the adult values (Andrew et al, 1990b;Riverdiau-Moalic et al, 1996;Williams, 2009). In the 30-to 36-week premature infant group plasminogen and a 2 AP are approximately 10% lower than the term infants with no significant differences in TPA or PAI.…”

“…Many different regimens have been described for systemic rTPA. Dosage advice varies from relatively high dose infusions of 0Á1-0Á6 mg/kg/h for arterial and for some cases of extensive venous thrombosis, usually administered over 6 h to low dose rTPA at 0Á01-0Á06 mg/kg/h for up to 48 h for venous thrombosis (Manco-Johnson, 2006;Williams, 2009;Monagle et al, 2012). Theoretically prolonged, low-dose regimens might allow for a longer duration of contact of rTPA with the thrombus and because rTPA preferentially acts on fibrin-bound plasminogen, i.e., acting on the clot surface, this may increase its effectiveness.…”

“…Because rTPA does not immediately affect clot propagation, heparin is sometimes used concomitantly, usually at a low dose of 10 lg/kg/h (Manco- Johnson, 2006;Williams, 2009).…”