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


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
  • 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
  • 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

Intravenous Dosing Of Thrombolytic Agents In Acute MI
(All patients with acute MI should receive one chewable aspirin 160-325 mg as soon as the diagnosis is suspected)
Drug Loading Dose Maintenance Dose Duration Of Infusion Concurrent Heparin
Streptokinase No 1.5 million IU (45 mL NaCl) 1 hr No
tPA (Alteplase) 15 mg 50 mg over 30 min** and 35 mg over next hr*** (100 mL sterile H2O) 90 min Yes
tPA (Reteplase) Given by 10 + 10 U double bolus, 10 U bolus over 2 min, wait 30 min and repeat 10 U over 2 min. 34 min Yes
tPA (Tenecteplase) 30-50 mg by single bolus body weight
(see package insert for precise dosing)
5-10 sec Yes
** 0.75 mg/Kg, not to exceed 50 mg over 30 min. *** 0.50 mg/Kg, not to exceed 35 mg over the next hour.

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.

Rapid Evaluation Of Patients With Suspected Acute Myocardial Infarction

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

Dosing Thrombolytic Agents In PE/DVT
Drug Indication Loading Dose Maintenance Dose Duration Of Infusion Concurrent Heparin
Streptokinase PE

DVT or arterial thromboembolism
250,000 IU over 30 min,
250,000 IU over 30 min
100,000 IU/hr

100,000 IU/hr

24 hrs.

24-72 hrs



tPA (Alteplase) PE None 100 mg 2hrs. Optional
Urokinase PE 2,000 IU/lb over 10 min 2,000 IU/lb/hr 12 hrs. NO

Interfacing Heparin And Thrombolytic Agents
Drug First Step Second Step Third Step Last Step
SK, UK Stop heparin Infusion Infuse thrombolytic agent in prescribed fashion Stop thrombolytic agent infusion Restart heparin Infusion with or without a loading dose when APTT or thrombin time returns to less than twice normal (usually after 3-4 hours)
tPA If it is elected to discontinue heparin during tPA Infusion for PE, follow directions for the other thrombolytic agents given above.