Thrombolysis with low dose tissue plasminogen activator.

Abstract

Two cases of vena caval thrombosis in infants were successfully treated with low dose (0-01-0-05 mg/kg/hour) local infusions oftissue plasminogen activator after conventional anticoagulant treatment had been unsuccessful. This approach is useful for clots associated with indwelling intravascular catheters, and a low dose infusion of tissue plasminogen activator as a regional application is recommended to achieve clot lysis with minimal systemic effects. (Arch Dis Child 1992;67:1483-4) An infusion ofrecombinant tissue plasminogen activator was started through the Hickman line at a dose of 0-01 mg/kg/hour. This was increased to 0-05 mg/kg/hour after four hours, and after 24 hours of treatment improvement in the swelling and oedema was noted. An ultrasound examination showed blood flow through the innominate veins and superior vena cava.After 48 hours of treatment there was some bleeding from the Hickman line insertion site. Six weeks after the operation an ultrasound examination of the inferior vena cava showed a large thrombus extending from the tip of a right femoral vein catheter and occupying most of the inferior vena cava. Warfarin was discontinued and recombinant tissue plasminogen activator given through the femoral vein catheter at an initial dose of 0 01 mg/kg/hour. This was increased to 0-02 mg/kg/hour after six hours and was continued for six days. Serial ultrasound examinations showed complete lysis of the clot over this period. The infant was then treated with an intravenous infusion of heparin followed by warfarin by mouth.There was no bleeding during the infusion of tissue plasminogen activator. The fibrinogen concentration was always greater than 1 5 g/l and the D-dimer concentration between 0-2 and 4 mg/I. Discussion Tissue plasminogen activator is a naturally occurring protein which plays a part in the fibrinolytic cascade. It catalyses the conversion of the inactive proenzyme plasminogen into the active serine protease plasmin. Tissue plasmino-

Pulmonary thrombo-embolism in nephrotic syndrome treated with tissue plasminogen activator

“…They recommended a dose of 0.1 mg/kg per hour, and experienced some bleeding complications at higher doses. Doyle et al [2] were successful in using rt-PA to treat two neonates with vena caval thrombosis who had not responded to heparin. Pyles et al [12] infused rt-PA with good eect into the left pulmonary artery of a child who developed pulmonary artery thrombosis despite continous heparin therapy for mild disseminated intravascular coagulation following cardiac surgery.…”

Management of a large organized intraatrial catheter-tip thrombus in a child with acquired immunodeficiency syndrome using escalating tissue plasminogen activator infusions

“…By infusing tPA through the central catheter, locally higher concentrations in proximity to the thrombus may have been achieved. The thrombolysis may have resulted in a manner similar to that described in clearing vena caval thrombi using local tPA infusions (18,19). The dissolution of the thrombus was likely gradual, and we did not observe any discrete cardiorespiratory event suggestive clinically of a large pulmonary embolus, although the possibility of microemboli cannot be ruled out.…”

Management of Preterm Infants with Intracardiac Thrombi

“…An identical concept has been successfully used with urokinase (1000 to 3000 U/kg/h) in preterm infants with intracardiac thrombosis [23] and tPA (0.01 to 0.05 mg/kg/h) in infants with vena cava thrombosis. [60,61] No complications such as cerebral haemorrhages were observed in any of these patients, with the exception of one being treated with tPA in whom the infusion caused a decrease in fibrinogen concentration and an increase in fibrin degradation products, indicating a systemic proteolytic state. Tissue plasminogen activator could, therefore, not be proven to cause less systemic effects than urokinase or streptokinase when used at low doses (as would be expected on theoretical grounds).…”

“…This might have some importance in the premature infant with physiologically low plasminogen and fibrinogen concentrations. [44] Amazingly, despite these advantages, tPA has only rarely been used in preterm infants with vena cava or intracardiac thrombosis (table I) [27,39,60] and it is only recently that two different groups reported the successful use of rt-PA in small series of neonates or preterm infants, respectively, with catheter-related thrombosis. [41,64] Bleeding complications were reported only by one group in a small number of patients.…”

“…Whether these thrombogenic circumstances dictate higher doses of antithrombotic agents such as urokinase or tissue plasminogen activator in neonatal than in adult thromboses is, however, open to question; thus, this concept has been questioned by others who showed effective fibrinolysis, although only in a small number of newborn infants, at much lower infrasystemic doses of urokinase, streptokinase or rt-PA, respectively. [23,[59][60][61] Actually, several different approaches in terms of the choice of the thrombolytic agent and the doses used are defended by different authors, usually based on their limited personal experience with a few patients. This is well reflected in table I, giving an overview of the published case reports and series of preterm infants presenting with intracardiac thrombosis treated with thrombolytic agents.…”