What are thrombolytics?

Thrombolytics: Mechanism, Types, and Clinical Applications

Thrombolytics are medications that dissolve blood clots by activating plasminogen to plasmin, which breaks down fibrin and dissolves thrombi to restore blood flow in occluded vessels. These agents are critical in the management of various thrombotic conditions including pulmonary embolism, acute ischemic stroke, and myocardial infarction 1.

Mechanism of Action

Thrombolytic agents work by:

• Converting plasminogen to plasmin
• Breaking down fibrin clots
• Restoring blood flow to ischemic tissues
• Reducing morbidity and mortality in thrombotic conditions

Types of Thrombolytic Agents

Fibrin-Specific Agents

• Recombinant tissue plasminogen activator (rtPA/Alteplase): Administered as 100 mg over 2 hours or 0.6 mg/kg over 15 minutes (maximum 50 mg) 2
• Tenecteplase (TNK): More fibrin-specific than rtPA, administered as a single bolus 3
• Reteplase: Enhanced fibrin specificity 2

Non-Fibrin-Specific Agents

• Streptokinase: 250,000 IU loading dose over 30 minutes, followed by 100,000 IU/h over 12-24 hours; alternatively, accelerated regimen of 1.5 million IU over 2 hours 2
• Urokinase: 4,400 IU/kg loading dose over 10 minutes, followed by 4,400 IU/kg/h over 12-24 hours; alternatively, accelerated regimen of 3 million IU over 2 hours 2

Key Differences Between Thrombolytic Agents

• Fibrin selectivity: rtPA and r-pro-UK are fibrin-selective and active primarily at the site of thrombosis, while streptokinase and urokinase are non-fibrin-selective and can cause systemic hypofibrinogenemia 2
• Half-life: Varies between agents, affecting administration protocols
• Stability: Different stability profiles impact storage and handling
• Administration: Some require continuous infusion while others can be given as bolus doses

Clinical Applications

Pulmonary Embolism (PE)

• High-risk PE: Thrombolytic therapy is first-line treatment for patients with cardiogenic shock and/or persistent arterial hypotension 2, 1
• Intermediate-risk PE: Thrombolysis may be considered in selected patients after careful consideration of bleeding risks 2, 1
• Low-risk PE: Thrombolytic therapy is not recommended 2

Acute Ischemic Stroke

• Used within specific time windows (typically within 3-4.5 hours of symptom onset)
• Alteplase is the most commonly used agent 2
• Higher risk of intracranial hemorrhage (6.4% to 20%) compared to other indications 4

Myocardial Infarction

• Most effective when administered within the first hour of symptom onset (50% reduction in mortality) 5
• Should be administered as soon as possible to eligible patients presenting within 12 hours of symptom onset 6

Contraindications

Absolute Contraindications 2, 1

• Hemorrhagic stroke or stroke of unknown origin at any time
• Ischemic stroke within the preceding 6 months
• Central nervous system damage or neoplasms
• Recent major trauma/surgery/head injury (within preceding 3 weeks)
• Gastrointestinal bleeding within the last month
• Known active bleeding
• Intracranial neoplasm, arteriovenous malformation, or aneurysm 3
• Severe uncontrolled hypertension 3

Relative Contraindications 2

• Transient ischemic attack in preceding 6 months
• Oral anticoagulant therapy
• Pregnancy or within 1 week postpartum
• Non-compressible punctures
• Traumatic resuscitation
• Refractory hypertension (systolic BP >180 mmHg)
• Advanced liver disease
• Infective endocarditis
• Active peptic ulcer

Complications and Risks

• Bleeding: The most common adverse effect, especially at arterial and venous puncture sites 1, 7
• Intracranial hemorrhage: Occurs in 1.5-2% of patients in clinical trials and up to 3-5% outside trials 1
• Hypersensitivity reactions: Including urticaria, anaphylaxis, and angioedema 7
• Thromboembolism: Increased risk in patients with high likelihood of left heart thrombus 7
• Cholesterol embolization: Rare but potentially fatal complication 7

Monitoring During Therapy

• Continuous hemodynamic monitoring
• Frequent neurological assessments
• Monitoring for signs of bleeding
• Serial hemoglobin measurements 1

Alternative Approaches

• Catheter-directed therapy: For patients with high bleeding risk or failed systemic thrombolysis 1
• Surgical embolectomy: For patients with contraindications to thrombolysis or who fail to respond to thrombolytic therapy 2, 1

Thrombolytic therapy represents a critical intervention for life-threatening thrombotic conditions, but requires careful patient selection and monitoring to balance the benefits of reperfusion against the risks of bleeding complications.