Dose:  0.1 mg/kg/hour
             Altepase or tPA dilution to restore catheter patency

Frequency: Continuous infusion

Comments: Alteplase is a tissue plasminogen activator (t-PA) produced by recombinant DNA from a human melanoma cell line. Alteplase is a proteolytic enzyme that binds to fibrin contained in a thrombus and converts entrapped plasminogen to plasmin. This initiates local fibrinolysis. Because of its low affinity for circulating plasminogen (as opposed to the plasminogen contained in the thrombus), systemic effects are anticipated to be minimal. When given at the site of the thrombus, its effectiveness is similar to systemic heparinization. Coagulation parameters do not change under t-PA therapy, except for fibrinogen that may lower in some cases. The half life of t-PA is 3 to 9 minutes. It is rapidly cleared by the liver, but minor elevations in liver enzymes can be associated with a marked prolongation of the half life. The drug can be administered systemically or locally if perfusion to the area of the thrombus is impaired. In newborn infants without liver dysfunction the following treatment protocol for t-PA may be recommended: a loading dose of 0.5 mg/kg over 10 minutes, followed by 0.1 mg/kg/hr IV infusion. If ultrasound examination shows no effect after 12 hours, increase the dose by 0.1 mg/kg/hr. Fibrinogen must be followed every 6 hours at first (plasmin can also degrade circulating fibrinogen and coagulation factors V and VIII). If it falls to less than 100 mg/dl, lower t-PA dose by 0.05 mg/kg/hr; if fibrinogen is more than 200 mg/dl, increase the dose by 0.1 mg/kg/hr. When fibrinogen levels are stabilized, measurements may be repeated every 24 hours. Do not load if liver dysfunction and do not increase by more than 0.05 mg/kg/hour. Treatment is stopped when complete resolution of the thrombus is achieved. At least three days of treatment must be completed before therapy may be considered as having no effect. Avoid intramuscular, deep venous, and arterial punctures during infusion. Successful fibrinolytic therapy is sometimes accompanied by simultaneous formation of a new thrombus leading to occlusion of the vessel. To prevent this, an infusion of heparin (10 units/kg/hr) given during and after the fibrinolytic therapy has been recommended.   More comments on alteplase.  Telephone number for consultation when caring for children with thromboembolic diseases 1-800-NO CLOTS. This is a free consultative service for physicians in North America from Dr. Maureen Andrew and her colleagues in Toronto.

Toxicity: Drugs that alter platelet function may increase the risk of bleeding, the most common adverse reaction. This occurs at incision or venipuncture sites, then from the GI or GU tracts. There have also been episodes of mild hypersensitivity reactions and urticaria (Facts and Comparisons, Inc. Drug Facts and Comparisons. Olin, B.R. ed. St. Louis, MO:Facts and Comparisons, Inc; 1997, page 88o). Smuts (Am J Perinatol 1996; 13:217) reviewed complications in case reports when t-PA was used in newborns. There were two cases of bleeding from venipuncture sites or from nose or GI tract that improved when the rate of infusion was decreased. There were two cases when there was an extension of a pre-existing IVH and two cases when pre-existing IVH was unchanged by treatment. In older children, agitation, restlessness, and crying are common.

Preparation:
Alteplase (Activase) is available in a 50 mg vial (29 million units). Dissolve 50 mg with 50 ml of sterile water for injection. This 1 mg/ml concentration can be further diluted with an equal volume of normal saline or D5W (0.5 mg/ml) just prior to infusion. The solution must be used within 8 hours of reconstitution. Do not use with other infusion solutions or drugs.

Alteplase can be used as a catheter clearing agent. A solution of 1 mg/ml is available from the pharmacy. 

Compatibility: Alteplase is compatible with D5W, lidocaine, morphine, and propranolol. It is incompatible with TPN, filter, dopamine, dobutamine, and presumably most other drugs.