Thrombolytic Therapy

In contrast to the anticoagulants heparin and warfarin, which function to prevent fibrin clot formation, the thrombolytic agents act to dissolve established thrombus by converting endogenous plasminogen to plasmin, which can lyse existing thrombus. Thrombolytic therapy should be considered for arterial thrombi using tissue plasminogen activator, urokinase, or streptokinase.

Tissue Plasminogen Activator

A t-PA infusion should be given at a rate of 0.5 mg/kg/h IV for 6 hours.

• Heparin should be given (20 units/kg/h) during t-PA infusion if the patient is not already on heparin.

• Following 6 hours of t-PA infusion and if there is no response to treatment, the plasminogen level should be determined. If the plasminogen level is low, fresh frozen plasma (FFP) 20 cc/kg IV q8h should be administered. A repeat infusion of t-PA may be considered.

Urokinase

Urokinase (UK) should be administered in a loading dose of 4000 units/kg over 10 minutes, followed by 4000 units/kg/h for 6 hours.

• Heparin should be given (20 units/kg/h) during UK infusion if the patient is not already on heparin.

• Following 6 hours of UK infusion and if there is no response to treatment, the plasminogen level should be determined. If the plasminogen level is low, FFP 20 cc/kg IV q8h should be administered. A repeat infusion of UK may be considered.

• Streptokinase can be administered when t-PA and UK are not available.

Streptokinase

Streptokinase (SK) should not be administered if it was used previously or if the plasminogen level is low (i.e., newborns). The loading dose consists of 4000 units/kg (maximum 250,000 units) over 10 minutes, followed by 2000 units/kg/h for 6 hours.

• Heparin should be given (20 units/kg/h) during SK infusion if the patient is not already on heparin.

• If there is no response to treatment, the plasminogen level should be determined. If the plasminogen level is low, FFP 20 cc/kg IV q8h should be given. UK or t-PA should be utilized (not SK) for further thrombolytic therapy.

• Patients must be premedicated with Tylenol and Benadryl before SK (repeat every 4-6 hours).

• Patients should not receive more than one course of SK because of the potential for allergic reactions. An anaphylactic reaction can occur in 1-2% of patients receiving SK. In the event of an anaphylactic reaction, discontinue SK immediately and administer epinephrine, steroids, and antihistamines.

Monitoring Response of Thrombolytic Therapy

• Obtain the PT and APTT every 6 hours.

• Determine the fibrinogen level and/or fibrin/fibrinogen degradation products (FDPs) or D-dimer, every 6 hours.

• Determine the plasminogen level at the end of the 6-hour infusion if there is no response or prior to proceeding to another course of therapy.

• The fibrinogen concentration may decrease by at least 20-50%; and the fibrino-gen concentration must be maintained at approximately 100 mg/dL by cryopre-cipitate infusions (1 unit/5 kg).

• When the fibrinogen concentration is less than 100 mg/dL and the patient is still receiving infusion of SK, UK, or t-PA, the dose of the thrombolytic agent should be decreased by 25%.

• The platelet count should be maintained at 100,000/m3 or higher.

• Six hours following thrombolytic therapy, heparin therapy may be sufficient for 24 hours before reinstituting thrombolytic therapy. There may be ongoing thrombolysis even in the absence of continued administration of the throm-bolytic agent.

Complications of Thrombolytic Therapy

Minor bleeding may occur in up to 50% of patients (i.e., oozing from a wound or puncture site). Supportive care and application of local pressure may be sufficient.

When severe bleeding occurs, the infusion of the thrombolytic agent should be terminated, and cryoprecipitate should be administered (usual dose of 1 unit/5 kg).

When life-threatening bleeding occurs, the infusion of the thrombolytic agent should be terminated. The fibrinolytic process can be reversed by infusing Amicar 100 mg/kg (maximum, 5 g) bolus, then 30 mg/kg/h (maximum, 1.25 g/h) until bleeding stops (maximum, 18 g/m2/day). Protamine sulfate may be required to reverse the heparin effect.

The following table lists the management of blocked central venous catheters (CVCs) using t-PA:

Weight Single-lumen CVC

Double-lumen CVC

Subcutaneous CVC (Mediport)

<10 kg 0.5 mg t-PA diluted in 0.9% NaCl to volume required to fill line.

>10 kg 1.0 mg t-PA in 1.0 mL 0.9% NaCl. Use amount required to fill volume of line, to maximum of 2 mL (2 mg t-PA).

0.5 mg t-PA diluted in 0.9% NaCl per lumen to fill volume of line. Treat one lumen at a time.

1.0 mg t-PA in 1.0 mL 0.9% NACl. Use amount required to fill volume of line, to a maximum of 2 mL (2 mg t-PA per lumen). Treat one lumen at a time.

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