Thrombolytic Therapy Considerations

Mechanisms and Risks

The breakdown of blood-brain barrier can occur due to fibrinolytic activity, increasing permeability, as stated by the American Heart Association 1
Reperfusion injury and vessel wall damage can result from rapid restoration of blood flow to ischemic areas, according to the American College of Cardiology 2
Systemic hypofibrinogenemia can occur due to tenecteplase, causing some degree of systemic fibrinolysis, as reported by the American Heart Association 3

The American College of Cardiology recommends strict adherence to contraindications, including previous intracranial hemorrhage, known cerebral vascular lesion, ischemic stroke within 3 months, active bleeding, and severe uncontrolled hypertension 2
The European Heart Journal suggests adhering to absolute contraindications, including previous intracranial hemorrhage, known structural cerebral vascular lesion, ischemic stroke within 3 months, active bleeding, and severe uncontrolled hypertension, to minimize tenecteplase-related bleeding risk 4, 5

Careful blood pressure management is necessary, with the American College of Cardiology recommending maintenance of SBP <180 mmHg and DBP <110 mmHg 2
More than 70% of bleeding episodes occur at vascular puncture sites, highlighting the importance of careful patient selection and avoidance of unnecessary invasive procedures, as emphasized by the European Society of Cardiology 6
The American Heart Association suggests stabilizing the patient by securing the airway, breathing, and circulation, establishing large-bore IV access, administering oxygen as needed, and positioning the patient appropriately, especially in cases of suspected intracranial hemorrhage 4
Frequent vital sign checks (every 15 minutes initially), serial hemoglobin/hematocrit measurements (every 4-6 hours until stable), coagulation studies (PT/INR, aPTT, fibrinogen) every 6 hours until normalized, and repeat imaging as clinically indicated to assess bleeding resolution are recommended, according to the European Heart Journal 4

The European Heart Journal recommends reversing anticoagulation by administering protamine sulfate (1 mg per 100 units of heparin given in the previous 2-3 hours) if concurrent heparin was administered, with a maximum single dose of 50 mg, and monitoring aPTT 7
Protamine partially neutralizes enoxaparin (1 mg protamine per 1 mg enoxaparin), as suggested by the European Heart Journal 4
The American College of Cardiology recommends administering cryoprecipitate (10 units) to replenish fibrinogen, fresh frozen plasma (15-20 mL/kg) to replace coagulation factors, and platelet transfusion if platelet count <100,000/μL or if on antiplatelet therapy, as suggested by the European Heart Journal 4, 7
Packed red blood cells should be administered for hemodynamic instability or significant drop in hemoglobin, according to the European Heart Journal 4, 7
The European Heart Journal suggests considering tranexamic acid (1 g IV over 10 minutes, followed by 1 g over 8 hours) as an antifibrinolytic therapy 7

In cases of intracranial hemorrhage, urgent neurosurgical consultation, consideration of reversal agents, control of blood pressure (SBP <140-160 mmHg), and urgent CT scan are recommended, as suggested by the Stroke journal 8
For gastrointestinal bleeding, endoscopic evaluation and intervention are necessary, while for access site bleeding, direct pressure, compression devices, or surgical repair may be required, according to the European Heart Journal 4
Retroperitoneal bleeding may require interventional radiology consultation for possible embolization, as suggested by the European Heart Journal 4
Reduced dosing in high-risk populations (elderly >75 years) should be considered, as suggested by the European Heart Journal 4, 5
Elderly patients (>75 years) have a higher risk of intracranial hemorrhage with tenecteplase and may require more aggressive management, as suggested by the European Heart Journal 4, 9
Patients on concurrent antiplatelet therapy (aspirin, clopidogrel) have an increased bleeding risk and may require platelet transfusion, according to the European Heart Journal 4
Renal impairment may prolong the half-life of tenecteplase and associated anticoagulants, requiring closer monitoring, as suggested by the European Heart Journal 4