What is the role of tenecteplase (tissue plasminogen activator) in treating high-risk or intermediate-high risk pulmonary embolism (PE) in patients with impaired renal function or other comorbidities?

Tenecteplase in Pulmonary Embolism

High-Risk PE: Clear Indication for Tenecteplase

Administer systemic thrombolytic therapy, including tenecteplase, immediately to all patients with high-risk PE (defined as hemodynamic instability with systolic BP <90 mmHg or cardiogenic shock). 1

• Tenecteplase is an acceptable alternative to alteplase (rtPA) for high-risk PE, with the standard dose being 100 mg over 2 hours or an accelerated regimen of 0.6 mg/kg over 15 minutes (maximum 50 mg) 1
• In high-risk PE, tenecteplase increases 30-day survival (16% vs 6% without thrombolysis, p=0.005) without significantly increasing bleeding complications 2
• Surgical pulmonary embolectomy should be performed if thrombolysis is absolutely contraindicated or has failed 1

Intermediate-Risk PE: Thrombolysis NOT Routinely Recommended

Do not routinely administer tenecteplase or any systemic thrombolysis as primary treatment in patients with intermediate-risk PE, even when right ventricular dysfunction or elevated cardiac biomarkers are present. 1, 3

Evidence Against Routine Use:

• The PEITHO trial (n=1,006) demonstrated that while tenecteplase reduced hemodynamic decompensation (1.6% vs 5.0%), it significantly increased major bleeding (6.3% vs 1.5%, p<0.001) and intracranial hemorrhage (2.0% vs 0.2%) 3
• No mortality benefit was observed at 7 days (2.4% vs 3.2%, p=0.42) or at 3-year follow-up, with no difference in persistent symptoms or chronic thromboembolic pulmonary hypertension rates 3
• Recent multicenter data shows tenecteplase has significantly higher major bleeding rates compared to alteplase (31.1% vs 10.9%, p=0.004) in intermediate-high risk PE 4

Rescue Thrombolysis Protocol:

Administer rescue thrombolytic therapy only if the patient develops hemodynamic deterioration while on adequate anticoagulation. 1, 3

Specific criteria for rescue tenecteplase include:

• Persistent hypotension (systolic BP <90 mmHg) 5, 6
• New requirement for vasopressor support 3, 5
• Clinical signs of cardiogenic shock 6
• Progressive hemodynamic deterioration with rising lactate or altered mental status 5

Management in Patients with Renal Impairment

In patients with severe renal impairment, initiate unfractionated heparin (UFH) immediately rather than LMWH or fondaparinux, targeting aPTT 1.5-2.5 times normal. 1, 5, 6

• Do not use NOACs in patients with severe renal impairment, as they are contraindicated 1, 5
• UFH is preferred because it does not accumulate renally and can be rapidly reversed if bleeding occurs 6
• Administer UFH as 80 U/kg IV bolus followed by 18 U/kg/h continuous infusion 6

Thrombolysis Considerations with Renal Dysfunction:

• The decision to use tenecteplase in intermediate-risk PE with renal impairment should be even more conservative, as bleeding risk is already elevated 5
• Reserve thrombolysis strictly for rescue therapy if hemodynamic collapse occurs despite adequate UFH anticoagulation 5

Management in Cancer Patients

For cancer-associated PE with intermediate risk, avoid routine tenecteplase and focus on optimal anticoagulation with LMWH once renal function permits. 5, 6

• LMWH is superior to warfarin for cancer-associated thrombosis and should be continued for at least 6 months, then indefinitely while cancer remains active 1, 6
• Transition from UFH to therapeutic-dose LMWH (dalteparin or enoxaparin) once creatinine clearance is >30 mL/min 6
• The combination of cancer, renal impairment, and intermediate-risk PE represents a particularly high bleeding risk scenario where routine thrombolysis is contraindicated 5

Contraindications to Tenecteplase

Absolute Contraindications: 1

• History of hemorrhagic stroke or stroke of unknown origin
• Ischemic stroke in previous 6 months
• Central nervous system neoplasm
• Major trauma, surgery, or head injury in previous 3 weeks
• Active bleeding
• Bleeding diathesis

Relative Contraindications: 1

• Transient ischemic attack in previous 6 months
• Oral anticoagulation (assess INR and bleeding risk)
• Refractory hypertension (systolic BP >180 mmHg)
• Advanced liver disease
• Active peptic ulcer

Monitoring Strategy for Intermediate-Risk PE

Implement close hemodynamic monitoring to identify patients requiring escalation to rescue thrombolysis. 3, 5

Monitor for:

• Serial vital signs with continuous telemetry 5
• Oxygen saturation and supplemental oxygen requirements 5
• Serial echocardiography to assess right ventricular function 5
• Cardiac biomarkers (troponin, BNP) to detect worsening myocardial injury 3
• Lactate levels as marker of tissue hypoperfusion 5

Hemodynamic Support Without Thrombolysis

Avoid aggressive fluid boluses in intermediate-risk PE, as they worsen right ventricular failure by increasing RV afterload. 5, 6

• Administer supplemental oxygen for hypoxemia (target SaO2 >90%) 1, 5
• Use vasopressors (norepinephrine and/or dobutamine) if hypotension develops, which signals need for rescue thrombolysis 1, 5, 6

Multidisciplinary Team Involvement

Consider activating a Pulmonary Embolism Response Team (PERT) for complex cases with multiple comorbidities, borderline hemodynamic instability, or contraindications to thrombolysis. 3, 5

PERT consultation is particularly valuable for:

• Intermediate-risk PE with severe RV dysfunction and refractory hypoxemia 3
• Patients with cancer, renal impairment, and intermediate-risk PE 5
• Progressive clinical deterioration on anticoagulation requiring consideration of catheter-directed interventions 3

Common Pitfalls to Avoid

• Do not administer tenecteplase prophylactically based solely on RV dysfunction or elevated biomarkers in stable intermediate-risk PE - bleeding risk outweighs theoretical benefit 3, 5
• Do not delay anticoagulation while awaiting complete diagnostic confirmation - start UFH or LMWH immediately if clinical probability is high or intermediate 3, 6
• Do not use aggressive fluid resuscitation - this worsens RV failure in PE patients 5, 6
• Do not prescribe DOACs to patients with severe renal impairment, pregnancy, or antiphospholipid syndrome 1, 5