Medical uses Tissue plasminogen activator

1 medical uses

1.1 ischemic stroke
1.2 pulmonary embolism
1.3 recombinant tissue plasminogen activators

medical uses

tpa used in cases of diseases feature blood clots, such pulmonary embolism, myocardial infarction, , stroke, in medical treatment called thrombolysis. common use ischemic stroke. can either administered systemically, in case of acute myocardial infarction, acute ischemic stroke, , cases of acute massive pulmonary embolism, or administered through arterial catheter directly site of occlusion in case of peripheral arterial thrombi , thrombi in proximal deep veins of leg.

a theoretical structure of full t-pa enzyme in humans. sugar residues light cyan-grey molecules, , different domains marked in different colours


ischemic stroke

there have been twelve large scale, high-quality trials of rtpa in acute ischemic stroke. meta-analysis of these trials concluded rtpa given within 6 hours of stroke increased odds of being alive , independent @ final follow-up, particularly in patients treated within 3 hours. however, there excess of mortality in treated patients in first week after event, intracranial haemorrhage @ 7 days mortality @ final follow not significant between treated , untreated patients.

it has been suggested if tpa effective in ischemic stroke, must administered possible after onset of stroke symptoms. indeed, tpa has become considered standard of care in acute ischemic stroke, long patient presents after onset of stroke symptoms. many national guidelines including aha have interpreted cohort of studies suggesting there specific subgroups may benefit tpa , recommend use within limited time window after event. protocol guidelines require use intravenously within first 3 hours of event, after detriments may outweigh benefits. example, canadian stroke network guideline states patients disabling acute ischemic stroke can treated within 4.5 hours of symptom onset should evaluated without delay determine eligibility treatment tpa. delayed presentation ed leads decreased eligibility; few 3% of people qualify treatment. in united states, window of administration used 3 hours onset of symptoms, newer guidelines recommend use 4.5 hours after symptom onset. tpa appears show benefit not large artery occlusions lacunar strokes. since tpa dissolves blood clots, there risk of hemorrhage use.

use of tpa in united states in treatment of patients eligible use, no contra-indications , arrival @ treating facility less 3 hours after onset of symptoms, reported have doubled 2003 2011. use on patients mild deficits, of nonwhite race/ethnicity, , oldest old age increased. however, many patients eligible treatment not treated.

tpa has been given patients acute ischemic stroke above age 90 years old. although small fraction of patients 90 years , above treated tpa acute ischemic stroke recover, patients have poor 30-day functional outcome or die. nonagenarians may octogenarians following treatment iv-tpa acute ischemic stroke. in addition, people frostbite treated tpa had fewer amputations not treated tpa.

there consensus amongst stroke specialists tpa standard of care eligible stroke patients , benefits outweigh risks. there significant debate in emergency medicine community regarding recombinant tpa s effectiveness in ischemic stroke. nnt group on evidence-based medicine concluded inappropriate combine these twelve trials single analysis, because of substantial clinical heterogeneity (i.e., variations in study design, setting, , population characteristics). examining each study individually, nnt group noted 2 of these studies showed benefit patients given tpa (and that, using analytical methods think flawed); 4 studies showed harm , had stopped before completion; , remaining studies showed neither benefit nor harm. on basis of evidence, nnt group recommended against use of tpa in acute ischaemic stroke. nnt group notes case 3-hour time window arises largely analysis of 2 trials: ninds-2 , subgroup results ist-3. however, presuming (0-3h) administration better later administration (3-4.5h or 4.5-6h) subgroup results of ist-3 suggest implausible biological effect in administration beneficial, 3-4.5h administration harmful, , 4.5-6h administration again beneficial. indeed, original publication of ist-3 trial found time-window effects not significant predictors of outcome (p=0.61). in uk, concerns stroke specialists have led review medicines , healthcare products regulatory agency.

pulmonary embolism

pulmonary embolism (blood clots have moved lung arteries) treated heparin followed warfarin. if pulmonary embolism causes severe instability due high pressure on heart ( massive pe ) , leads low blood pressure, recombinant tpa recommended.

recombinant tissue plasminogen activators

recombinant tissue plasminogen activators (r-tpas) include alteplase, reteplase, , tenecteplase (tnkase).

activase (alteplase) fda-approved treatment of myocardial infarction st-elevation (stemi), acute ischemic stroke (ais), acute massive pulmonary embolism, , central venous access devices (cvad).

reteplase fda-approved acute myocardial infarction, has more convenient administration , faster thrombolysis alteplase. because second generation engineered tpa, hence half life 20 minutes allows administered bolus injection rather infusion alteplase.

tenecteplase indicated in acute myocardial infarction, showing fewer bleeding complications otherwise similar mortality rates after 1 year compared alteplase.

additional r-tpas, such desmoteplase, under clinical development.