What are the guidelines for using alteplase (tissue plasminogen activator) and dornase (deoxyribonuclease) alpha together?

Guidelines for Using Alteplase and Dornase Alpha Together

There are currently no specific guidelines addressing the combined use of alteplase (tissue plasminogen activator) and dornase alpha (deoxyribonuclease) for systemic administration, but their combination has shown effectiveness in treating complex pleural effusions and empyema.

Intrapleural Use of Alteplase and Dornase Alpha

Evidence for Combined Use

• The combination of intrapleural alteplase and dornase alpha has been shown to be more effective in treating empyema than either agent alone in experimental models 1
• A modified low-dose protocol of 5 mg alteplase with 5 mg dornase alfa has been successfully used to drain complex hemoserous malignant pleural effusions in patients with anemia without significant risk of intrapleural bleeding 2
• The combination therapy has been safely used with a modified protocol in pregnant patients with complicated parapneumonic effusions, suggesting its safety can be maintained even in high-risk populations 3

Mechanism of Action

• Alteplase (tPA) acts as a fibrinolytic agent that breaks down fibrin clots 1
• Dornase alpha (DNase) breaks down extracellular DNA that contributes to the viscosity of purulent collections 1
• When used together, alteplase disrupts the fibrin network while dornase alpha reduces the viscosity of the fluid, resulting in more effective drainage 1

Alteplase Administration Guidelines (When Used Alone)

Indications and Timing

• IV alteplase (0.9 mg/kg, maximum dose 90 mg) is recommended for selected patients with acute ischemic stroke within 3 hours of symptom onset 4
• Treatment can be extended to 3-4.5 hours in selected patients ≤80 years of age without a history of both diabetes mellitus and prior stroke, with NIHSS score ≤25, not taking oral anticoagulants, and without imaging evidence of ischemic injury involving more than one-third of the MCA territory 4
• Treatment should be initiated as quickly as possible as time to treatment is strongly associated with outcomes 4

Contraindications

• Evidence of intracranial hemorrhage on CT 4
• Severe head trauma within 3 months 4
• Ischemic stroke within 3 months 4
• History of intracranial hemorrhage 4
• Coagulopathy (platelets <100,000/mm³, INR >1.7, aPTT >40 s, or PT >15 s) 4
• Treatment with low molecular weight heparin within the previous 24 hours 4
• Active internal bleeding or recent (within 21 days) gastrointestinal or urinary tract hemorrhage 4

Special Considerations

• Blood pressure should be lowered safely to <185/110 mm Hg before starting IV alteplase 4
• In patients treated with alteplase for stroke, initiation of antiplatelet agents should be delayed until after the 24-hour post-thrombolysis scan has excluded intracranial hemorrhage 4

Practical Considerations for Combined Use

• Dosing: When used together for intrapleural administration, a modified low-dose protocol of 5 mg alteplase with 5 mg dornase alfa has been reported as effective and safe 2
• Timing: In experimental models, the combination was administered every 12 hours for a total of six treatments 1
• Monitoring: Close monitoring for bleeding complications is essential, especially in patients with pre-existing coagulopathies or those at high risk for bleeding 2, 3
• Precautions: The combination therapy produces larger volumes of pleural fluid compared to either agent alone or saline, which may necessitate more frequent drainage 1

Emerging Alternatives

• Recent evidence suggests tenecteplase may be non-inferior to alteplase for acute ischemic stroke treatment, with logistical advantages of single bolus administration versus the 1-hour infusion required for alteplase 5
• This may impact future guidelines regarding thrombolytic therapy, though specific recommendations regarding combination with dornase alpha have not been established 5

Important Caveats

• Most evidence for combined alteplase and dornase alpha use comes from intrapleural administration for empyema or complex pleural effusions, not systemic administration 2, 1, 3
• There are no established guidelines for systemic co-administration of these agents
• When considering combined use, the bleeding risk associated with alteplase must be carefully weighed against potential benefits 2, 3