Thrombolytic Therapy

Thrombolytic agents are proteins that activate a plasma proenzyme, plasminogen, to the active enzyme plasmin. Plasmin then solubilizes fibrin and degrades a number of other plasma proteins, most notably fibrogen.

Agents Available And Indications

Agents

Streptokinase (SK)- Derived from group C, ß-hemolytic streptococci. Not fibrin specific. Activates adjacent plasminogen by forming a non-covalent SK-plasminogen activator complex. Plasma half-life 30 min. Stimulates antibody production making retreatment difficult.

Urokinase (UK)- Derived from cultured human cells. Not fibrin specific. Activates plasminogen directly by enzymatic action. Plasma half-life 20 min.

Tissue Plasminogen Activator- Derived by recombinant genetics from human DNA. Fibrin specific. Activates plasminogen associated with fibrin directly by enzymatic action. Short plasma half-life. Two preparations of tPA are available.

• Alteplase (tPA) is the glycosylated protein of 527 amino acids produced by recombinant DNA technology.

• Reteplase (sometimes called rPA) is the 39,571 molecular weight non-glycosylated deletion mutein of tPA. It contains 355 of the 527 amino acids of native tPA and includes the kringle 2 and the protease domains of the parent molecule.

• Tenecteplase is the 527 amino acid protein produced by recombinant DNA technology. It differs from alteplase by 6 amino acids
  

Indications

• Acute myocardial infarction- streptokinase, tPA (Alteplase, Reteplase & Tenecteplase)
• Acute ischemic stroke - tPA (Alteplase)
• Acute pulmonary embolism - SK, UK, tPA (Alteplase)
• Acute deep venous thrombosis - SK
• Clotted AV fistula and shunts - UK

Precautions

• Bleeding is the major complication of thrombolytic therapy. Consequently, absolute contraindications include dissecting aortic aneurysm, pericarditis, stroke, or neurosurgical procedures within 6 months or known intracranial neoplasm. Relative contraindications include major surgery or bleeding within 6 weeks, known bleeding diathesis, and severe uncontrolled hypertension.
• Allergic reactions: SK and anistreplase are potentially allerogenic. Patients are usually pretreated with intravenous hydrocortisone 100 mg.
• Antibody production: SK and anistreplase induce antibody production, which makes retreatment with either of these agents less effective.

 

Thrombolytic Therapy In Myocardial Infarction

Other Regimens For Thrombolytic Agents

Peripheral Intra-arterial Infusion

SK: 20,000 IU bolus followed by 2,000 IU/min for 60 min.

UK: 6,000 IU/min for 1-2 hrs. (Both SK and UK should be given with concurrent systemic heparin.)

Clotted IV Catheter Clearance with UK

Inject UK 5,000 IU in 1 mL into catheter. For central venous catheter inject 5,000 IU/mL in volume equal to volume of the catheter. Allow 30-60 min for thrombolysis.

 

Clotted AV Cannula Clearance with SK

Inject SK 250,000 in 2 mL in each end of cannula. Clamp ends and allow 30-60 min for thrombolysis.

Chest pain or other symptoms suggestive of acute myocardial ischemia

ECG shows one of these: ST-segment elevation >0.1 mV in at least 2 contiguous leads New or presumed new left bundle branch block ST depression with prominent R wave in V2-V3, if thought to represent posterior MI

Give one chewable aspirin 160 mg - 325 mg

Confirm absence of contraindications to thrombolytic agents*

Symptoms present less than 6 hrs.	Symptoms present between 6 & 12 hrs.	Symptoms present more than 12 hrs.
Give thrombolytic agent, therapy most beneficial	Strongly consider thrombolytic agent, therapy moderately beneficial	Therapy less effective, but consider if pain continues or recurs

* See section on indications. Thrombolytic agents seem to offer less benefits in patients over 75 although age is not a contraindication.

Thrombolytic Therapy In Ischemic Stroke

Dosing tPA (Alteplase) In Acute Ischemic Stroke

Inclusion Criteria

• Duration of symptoms and findings less than 3 hours
• CT scan of head shows no intracranial bleeding
• Blood pressure not higher than 185/100 mm Hg (BP must be kept below 185/110 mm Hg during and after therapy)

tPA (Alteplase) Dose

• 0.9 mg/kg IV over one hour (no concurrent heparin or aspirin)

Note: Patients must be carefully selected and treated within 3 hours. Other thrombolytic agents cannot be substituted for tPA. Please refer to the reference given below before using tPA in ischemic stroke.

Clinical debate: should thrombolytic therapy be the first-line treatment of acute ischemic stroke? New England Journal Of Medicine 1997; 337:1309-13

 

Thrombolytic Therapy In Pulmonary Embolism and Deep Venous Thrombosis