III. Mechanism

  1. Tissue Plasminogen Activator (tPA)
    1. Serine protease binds Fibrin and activates Fibrin-bound plasminogen to plasmin
    2. Plasmin breaks down both Fibrin and Fibrinogen to Fibrin
      1. Fibrin Degradation Products result, which in turn also act to inhibit Fibrin formation
    3. tPA has been replaced by recombinant products (r-tPA)
      1. tPA was originally synthesized and extracted from cultured mammalian cells
  2. Recombinant Tissue Plasminogen Activator (r-tPA)
    1. Alteplase (Activase)
    2. Reteplase (Retavase)
    3. Tenectaplase (TNKase, TNK tPA)

IV. Dosing

  1. Myocardial Infarction
    1. See Thrombolysis in ST Elevation Myocardial Infarction
    2. Bolus: 15 mg IV THEN
    3. Next: 0.75 mg/kg (max 50 mg) over 30 minutes THEN
    4. Next: 0.5 mg/kg (max 35 mg) over next 60 minutes
    5. Administer adjunctive Heparin concurrently
      1. See Thrombolysis
  2. Acute Ischemic Cerebrovascular Accident
    1. See Thrombolysis in Cerebrovascular Accident
    2. Calculate total dose: 0.9 mg/kg (max 90 mg)
    3. Bolus: Give 10% total dose as IV bolus over 1 minute
    4. Next: Give remainder of total dose over 60 minutes
  3. Acute Massive Pulmonary Embolus
    1. See Thrombolysis in Massive Pulmonary Embolism
    2. Pulse present
      1. First: 10 mg IV bolus
      2. Next: 90 mg IV over 2 hours
    3. Pulse absent
      1. tPA 50 mg IV bolus and continue CPR for at least 30 minutes (to allow for tPA circulation)
    4. Restart Heparin when PTT below twice normal
  4. Occluded central venous access
    1. Administer 2 mg/ml via occluded catheter for 2 hours
    2. May repeat once if refractory to first dose

V. Efficacy

  1. Disadvantages (compared with other Thrombolytics)
    1. Increased bleeding risk
      1. 3-4% greater risk of bleeding in older than age 75
    2. Re-occludes earlier than other Thrombolytics
      1. Needs Heparin concurrently and afterward
  2. Advantages (compared with other Thrombolytics)
    1. Probably reperfuses arteries earlier
    2. Superior in large, anterior Myocardial Infarctions

VI. Safety

  1. Unknown safety in pregnancy
  2. Unknown safety in Lactation

VII. Drug Interactions

  1. ACE Inhibitor
    1. Increased Angioedema risk when tPA is used

Images: Related links to external sites (from Bing)

Related Studies

Ontology: Alteplase (C0032143)

Definition (MSH) A proteolytic enzyme in the serine protease family found in many tissues which converts PLASMINOGEN to FIBRINOLYSIN. It has fibrin-binding activity and is immunologically different from UROKINASE-TYPE PLASMINOGEN ACTIVATOR. The primary sequence, composed of 527 amino acids, is identical in both the naturally occurring and synthetic proteases.
Definition (CHV) a kind of clot-dissolving enzyme
Definition (CHV) a kind of clot-dissolving enzyme
Definition (CHV) a kind of clot-dissolving enzyme
Definition (CHV) a kind of clot-dissolving enzyme
Definition (CHV) a kind of clot-dissolving enzyme
Definition (NCI_NCI-GLOSS) A form of tissue plasminogen activator that is made in the laboratory. It helps dissolve blood clots and is used to treat heart attacks, strokes, and clots in the lungs. It is also being studied in the treatment of cancer. It is a type of systemic thrombolytic agent.
Definition (NCI) A recombinant therapeutic agent which is chemically identical to or similar to endogenous tissue plasminogen activator (tPA). tPA is a serine protease which converts plasminogen to plasmin, a fibrinolytic enzyme. Upon administration, alteplase increases plasmin enzymatic activity, resulting in hyperfibrinolysis and potential dissolution of a thrombus or embolism.
Definition (PDQ) A recombinant therapeutic agent which is chemically identical to or similar to endogenous tissue plasminogen activator (tPA). tPA is a serine protease which converts plasminogen to plasmin, a fibrinolytic enzyme. Upon administration, recombinant tPA increases plasmin enzymatic activity, resulting in hyperfibrinolysis and potential dissolution of a thrombus or embolism. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42033&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42033&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C39607" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Amino Acid, Peptide, or Protein (T116) , Enzyme (T126)
MSH D010959
SnomedCT 391744002, 130625007, 386956006, 27638005, 387152000, 37411004, 108997009
LNC LP16891-1, MTHU019721
English Alteplase, Plasminogen Activator, Tissue, Plasminogen Activator, Tissue Type, Plasminogen Activator, Tissue-Type, Tissue Activator D 44, Tissue Activator D-44, Tissue Plasminogen Activator, Tissue Type Plasminogen Activator, Tissue-Type Plasminogen Activator, T-PA - tissue plasm activator, Tissue-type plasminogen activator, rt-PA, t-PA, recombinant tissue plasminogen activator, TPA (tissue plasminogen activator), tissue plasminogen activator, tissue plasminogen activator (medication), thrombolytics tissue plasminogen activator, TTPA, tPA (tissue plasminogen activator), alteplase, alteplase, recombinant, Tisokinase, T Plasminogen Activator, T-Plasminogen Activator, Recombinant Tissue Plasminogen Activator, Plasminogen Activator (Human Tissue-Type Protein Moiety), Tissue Plasminogen Activator [Chemical/Ingredient], t-plasminogen activator, t-pa, tpa, ALTEPLASE, EC 3.4.21.68, Alteplase - chemical (substance), T-plasminogen activator (substance), T-plasminogen activator, Alteplase - chemical, Tissue plasminogen activator preparation (substance), Plasminogen activator tissue type, Activase, r-tPA, tPA, T-PA, T-PA - tissue-type plasminogen activator, Tissue plasminogen activator, Tissue-type plasminogen activator preparation, rt-PA preparation, t-PA preparation, Alteplase (product), Alteplase (substance), Tissue plasminogen activator (substance), Tissue plasminogen activator preparation (product), Tissue plasminogen activator preparation, TPA, PLAT, ALTEPLASE,RECOMBINANT
Swedish Vävnadsplasminogenaktivator
Czech alteplasa, plasminogen - aktivátor tkáňového typu
Finnish Kudoksen plasminogeenin aktivaattori
Italian Attivatore del plasminogeno T, Attivatore del plasminogeno di tipo tissutale, tPA, Attivatore tissutale D-44, Attivatore del plasminogeno tissutale
Russian ALTEPLAZA, PLAZMINOGENA TKANI AKTIVATOR, PLAZMINOGENA AKTIVATOR TKANEVOGO TIPA, АЛТЕПЛАЗА, ПЛАЗМИНОГЕНА АКТИВАТОР ТКАНЕВОГО ТИПА, ПЛАЗМИНОГЕНА ТКАНИ АКТИВАТОР
Japanese プラスミノーゲン活性化物質-組織型, グルトパ注, 組織プラスミノーゲンアクチベーター, 組織プラスミノゲンアクチベーター, 組織プラスミノゲンアクチベータ, 組織型プラスミノーゲン活性化物質, アクチバシン, 組織プラスミノーゲンアクチベータ, Grtpa注, アルテプラーゼ
Spanish activador del plasminógeno tisular (producto), preparado con activador del plasminógeno tisular (producto), preparado con activador del plasminógeno tisular, Activador de Plasminógeno Tipo Tisular, activador del plasminógeno - T, preparado de activador tisular del plasminógeno (sustancia), preparado de activador tisular del plasminógeno, activador del plasminógeno - T (sustancia), TPA, activador del plasminógeno hístico, activador del plasminógeno tisular (sustancia), activador del plasminógeno tisular, alteplasa (producto), alteplasa (sustancia), alteplasa, preparado de TPA, preparado de activador del plasminógeno tipo tisular, preparado de activador del plasminógeno tisular (sustancia), preparado de rt-PA, preparado de t-PA, Alteplasa, Activador de Plasminógeno T, Activador de Tejido Plasminógeno
French tPA (tissue Plasminogen Activator), Activateur tissulaire du plasminogène, t-PA (t-Plasminogen Activator), Altéplase
Polish t-PA, Aktywator plazminogenu tkankowy, Tkankowy aktywator plazminogenu, Alteplaza
Croatian Tkivni aktivator plazminogena
German Gewebe-Plasminogen-Aktivator, Gewebetyp-Plasminogen-Aktivator, Plasminogen-Aktivator, Gewebetyp, Alteplase, T-Plasminogen-Aktivator
Portuguese Alteplase, Ativador de Plaminogênio T, Ativador de Plasminogênio Tecidual, Ativador de Plasminogênio Tipo Tecidual

Ontology: Activase (C0701942)

Concepts Pharmacologic Substance (T121) , Amino Acid, Peptide, or Protein (T116) , Enzyme (T126)
MSH D010959
French Activase
English activase, Alteplase Genentech Brand, Genentech Brand of Alteplase, Hoffmann La Roche Brand of Alteplase, Hoffmann-La Roche Brand of Alteplase, Activase

Ontology: Tissue Plasminogen Activators [MoA] (C1383102)

Concepts Molecular Function (T044)
English Tissue Plasminogen Activators [MoA], Tissue Plasminogen Activators