What is the reversal for Tenecteplase (TNK-tissue plasminogen activator)?

Reversal of Tenecteplase (TNK)

There is no specific reversal agent for tenecteplase; management relies on supportive care, discontinuation of the drug, and administration of antifibrinolytic agents (cryoprecipitate, fresh frozen plasma, or tranexamic acid) for life-threatening bleeding complications. 1

Key Pharmacologic Characteristics

Tenecteplase is a genetically engineered tissue plasminogen activator with a terminal half-life of 65-132 minutes and initial disposition half-life of 17-24 minutes, meaning the drug's fibrinolytic effects dissipate relatively quickly after administration. 2 Unlike streptokinase, TNK does not cause antibody formation and is not associated with hypotension or severe allergic reactions requiring reversal. 1, 3

Management of Major Bleeding Complications

Immediate Actions

• Stop any ongoing infusion immediately (though TNK is typically given as a single bolus). 3
• Assess the bleeding source and severity - intracranial hemorrhage occurs in approximately 1-2% of patients, while major non-cerebral bleeding occurs in 4-6%. 1
• Obtain emergency imaging for suspected intracranial hemorrhage. 1

Pharmacologic Interventions for Life-Threatening Bleeding

Administer cryoprecipitate (10 units) or fresh frozen plasma (2-4 units) to replace fibrinogen and clotting factors depleted by fibrinolysis. 1 Cryoprecipitate is preferred as it provides concentrated fibrinogen without excessive volume.

Consider tranexamic acid (1 gram IV over 10 minutes) as an antifibrinolytic agent to inhibit plasminogen activation and stabilize clot formation. 1 This is particularly relevant given TNK's mechanism as a plasminogen activator.

Platelet transfusion may be necessary if thrombocytopenia is present or if the patient was on antiplatelet therapy. 1

Special Considerations for Anticoagulated Patients

Dabigatran Reversal Before TNK

If a patient on dabigatran requires TNK for acute ischemic stroke, administer idarucizumab (5 grams IV) to reverse dabigatran before giving tenecteplase. 4 A case series of 13 patients demonstrated this approach was safe with no symptomatic hemorrhagic transformation and 62% achieving favorable functional outcomes. 4

Other Anticoagulants

For patients on direct factor Xa inhibitors (rivaroxaban, apixaban) or warfarin who develop bleeding after TNK, standard reversal protocols apply: prothrombin complex concentrate (PCC) for warfarin or factor Xa inhibitors, with dosing based on the specific agent and INR if applicable. 1

Hypotension Management (Not a Reversal Issue)

TNK does not typically cause hypotension unlike streptokinase, but if hypotension develops, stop the infusion, position the patient flat with legs elevated, and assess for alternative causes including cardiogenic shock, right ventricular infarction, or bleeding. 3 Atropine or IV crystalloids may be needed based on the underlying cause. 1, 3

Critical Pitfalls to Avoid

• Do not confuse TNK with streptokinase - streptokinase causes antibodies and hypotension requiring specific management, while TNK does not. 1, 3
• Do not delay supportive care waiting for a "reversal agent" - none exists, and time is critical in managing bleeding complications. 1
• Monitor high-risk patients closely: elderly patients, those with low body weight, females, and patients with uncontrolled hypertension have higher bleeding risk. 1, 5
• Weight-based dosing errors up to 20 kg do not increase ICH risk, but verify dosing was appropriate (30-50 mg based on weight). 1, 5