What is an alternative lytic agent to streptokinase (Streptokinase) for prosthetic valve thrombosis?

Alternative Lytic Agent to Streptokinase for Prosthetic Valve Thrombosis

Urokinase is the preferred alternative to streptokinase for prosthetic valve thrombosis, administered at 4,400 U/kg per hour using the same dosing protocol as for pulmonary embolism. 1

Primary Alternative: Urokinase

Patients with known allergy to streptokinase or those who have been previously exposed to streptokinase should be given urokinase. 1 This is particularly important because previous exposure to streptokinase or APSAC (anistreplase) is an absolute contraindication to reusing any streptokinase-containing agent. 1

Dosing Protocol for Urokinase

• Administer urokinase at 4,400 U/kg per hour, using the same protocol established for pulmonary embolism treatment 1
• Continue infusion until hemodynamic improvement is achieved or thrombus disappears on echocardiography 1

Comparative Efficacy

• Streptokinase and urokinase have been the most commonly used fibrinolytic agents with no statistically significant difference in their success rates 1
• In a large single-center study of 127 cases, when streptokinase or rtPA were used as first-line agents, they appeared significantly superior to urokinase in terms of valve reopening 2
• However, urokinase remains the guideline-recommended alternative when streptokinase cannot be used 1

Secondary Alternative: Recombinant Tissue Plasminogen Activator (rt-PA)

While rt-PA has been used for prosthetic valve thrombosis, the guidelines express significant concern about its safety profile compared to streptokinase and urokinase. 1

Safety Concerns with rt-PA

• Two fatal strokes and one additional death occurred in 21 patients treated for prosthetic valve thrombosis with rt-PA 1
• rt-PA is more costly and no advantage over streptokinase or urokinase has been demonstrated for valve thrombosis 1
• Despite these concerns, rt-PA has been used successfully in some cases, particularly in pediatric patients 3

When rt-PA Might Be Considered

• In patients with contraindications to both streptokinase and urokinase 2
• When used in doses established for pulmonary embolism treatment 1
• In recurrent thrombosis after failure of other agents 2

Monitoring During Thrombolytic Therapy

Regardless of which agent is used, perform Doppler echocardiography every 2 to 3 hours in obstructive prosthetic valve thrombosis to monitor hemodynamic response. 1

Duration of Treatment

• Stop thrombolytic infusion when pressure gradient and valve area return to normal or near normal 1
• If no hemodynamic improvement occurs at 24 hours, or after 72 hours even without complete recovery, discontinue the lytic agent 1
• Treatment duration has varied between 2 and 120 hours in reported cases 1

For Nonobstructive Thrombosis

• Perform transesophageal echocardiography (TEE) at 24 hours, and repeat at 48 and 72 hours if thrombus persists 1
• TEE is the only useful technique for monitoring treatment in nonobstructive cases 1

Critical Safety Considerations

Absolute Contraindications to Any Thrombolytic

• Active internal bleeding 1
• History of hemorrhagic stroke 1
• Recent cranial trauma or neoplasm 1
• Blood pressure >200/120 mm Hg 1
• Diabetic hemorrhagic retinopathy 1

Management of Complications

• If neurological symptoms of stroke develop, immediately stop thrombolytic treatment and perform urgent CT scan of the brain to exclude hemorrhage 4
• For peripheral embolism during treatment, continue thrombolytic therapy followed by antithrombotic therapy regardless of hemodynamic results 4
• Do not use adjuvant anticoagulation during active thrombolytic infusion 4

Common Pitfalls to Avoid

• Do not use rt-PA as a first-line alternative given the documented increased mortality risk compared to streptokinase and urokinase 1
• Do not readminister streptokinase in patients with previous exposure due to antibody formation and risk of allergic reactions 1
• Do not delay treatment while debating agent selection in hemodynamically unstable patients—urokinase should be initiated promptly when streptokinase is contraindicated 1