The main complication is bleeding (which can be dangerous), and in some situations thrombolysis may therefore be unsuitable. Thrombolysis can also play an important part in reperfusion therapy that deals specifically with blocked arteries.
Diseases where thrombolysis is used:
- ST elevation myocardial infarction: Large trials have shown that mortality can be reduced using thrombolysis (particularly fibrinolysis) in treating heart attacks. It works by stimulating secondary fibrinolysis by plasmin through infusion of analogs of tissue plasminogen activator (tPA), the protein that normally activates plasmin.
- Stroke: Thrombolysis reduces major disability or death when given within 3 hours (or perhaps even 6 hours) of ischaemic stroke onset when there are no contraindications to treatment.
- Massive pulmonary embolism. For the treatment of a massive pulmonary embolism, catheter-directed therapy is a safer and more effective alternative to systemic thrombolysis. This involves the injecting of drugs directly into the clot.
- Severe deep vein thrombosis
- Acute limb ischaemia
Thrombolysis is usually intravenous. It may also be used directly into the affected blood vessel during an angiogram (intra-arterial thrombolysis), e.g. when patients present with stroke beyond three hours or in severe deep vein thrombosis (catheter-directed thrombolysis).
Thrombolysis is performed by many types of medical specialists, including interventional radiologists, vascular surgeons, cardiologists, interventional neuroradiologists, and neurosurgeons. In some countries such as the United States of America, emergency medical technicians may administer thrombolytics for heart attacks in prehospital settings, by on-line medical direction. In countries with more extensive and independent qualifications, prehospital thrombolysis (fibrinolysis) may be initiated by the emergency care practitioner (ECP). Other countries which employ ECP's include, South Africa, the United Kingdom, and New Zealand. Prehospital thrombolysis is always the result of a risk-benefit calculation of the heart attack, thrombolysis risks, and primary percutaneous coronary intervention (pPCI) availability.
Thrombolysis is not without risks. Therefore, clinicians must select patients who are to be best suited for the procedure, and those who have the least risk of having a fatal complication. An absolute contraindication is in itself enough to avoid thrombolysis, while a relative contraindication needs to be considered in relation to the overall clinical situation.
- Any previous history of hemorrhagic stroke, ischemic stroke within 3 months.
- History of stroke, dementia, or central nervous system damage within 1 year
- Head trauma within 3 weeks or brain surgery within 6 months
- Known intracranial neoplasm
- Suspected aortic dissection
- Internal bleeding within 6 weeks
- Active bleeding or known bleeding disorder
- Traumatic cardiopulmonary resuscitation within 3 weeks
- Oral anticoagulant therapy
- Acute pancreatitis
- Pregnancy or within 1 week postpartum
- Active peptic ulceration
- Transient ischemic attack within 6 months
- Infective endocarditis
- Active cavitating pulmonary tuberculosis
- Advanced liver disease
- Intracardiac thrombi
- Uncontrolled hypertension (systolic blood pressure >180 mm Hg, diastolic blood pressure >110 mm Hg)
- Puncture of noncompressible blood vessel within 2 weeks
- Previous streptokinase therapy
Major surgery, trauma, or bleeding within 2 weeks
- Uncertainty about time of stroke onset (e.g. patients awakening from sleep).
- Coma or severe obtundation with fixed eye deviation and complete hemiplegia.
- Hypertension: systolic blood pressure ≥ 185mmHg; or diastolic blood pressure >110mmHg on repeated measures prior to study. (if reversed, patient can be treated)
- Clinical presentation suggestive of subarachnoid haemorrhage even if the CT scan is normal.
- Presumed septic embolus.
- Patient having received a heparin medication within the last 48 hours and has an elevated Activated Prothrombin Time (APTT) or has a known hereditary or acquired haemorrhagic diathesis
- INR >1.7
- Known advanced liver disease, advanced right heart failure, or anticoagulation, and INR > 1.5 (no need to wait for INR result in the absence of the former three conditions).
- Known platelet count <100,000 uL.
- Serum glucose is < 2.8 mmol/l or >22.0 mmol/l.
- Severe neurological impairment with NIHSS score >22.
- Age >80 years.
- CT evidence of extensive middle cerebral artery (MCA) territory infarction (sulcal effacement or blurring of grey-white junction in greater than 1/3 of MCA territory).
- Stroke or serious head trauma within the past three months where the risks of bleeding are considered to outweigh the benefits of therapy.
- Major surgery within the last 14 days (consider intra-arterial thrombolysis).
- Patient has a known history of intracranial haemorrhage, subarachnoid haemorrhage, known intracranial arteriovenous malformation or previously known intracranial neoplasm
- Suspected recent (within 30 days) myocardial infarction.
- Recent (within 30 days) biopsy of a parenchymal organ or surgery that, in the opinion of the responsible clinician, would increase the risk of unmanageable (e.g. uncontrolled by local pressure) bleeding.
- Recent (within 30 days) trauma with internal injuries or ulcerative wounds.
- Gastrointestinal or urinary tract haemorrhage within the last 30 days or any active or recent haemorrhage that, in the opinion of the responsible clinician, would increase the risk of unmanageable (e.g. by local pressure) bleeding.
- Arterial puncture at non-compressible site within the last 7 days.
- Concomitant serious, advanced or terminal illness or any other condition that, in the opinion of the responsible clinician would pose an unacceptable risk.
- Minor or Rapidly improving deficit.
- Seizure: If the presenting neurological deficit is deemed due to a seizure.
- Pregnancy is not an absolute contraindication. Consider intra-arterial thrombolysis.
Hemorrhagic stroke is a rare but serious complication of thrombolytic therapy. If a patient has had thrombolysis before, an allergy against the thrombolytic drug may have developed (especially after streptokinase). If the symptoms are mild, the infusion is stopped and the patient is commenced on an antihistamine before infusion is recommenced. Anaphylaxis generally requires immediate cessation of thrombolysis.
Thrombolysis therapy uses thrombolytic drugs that dissolve blood clots. Most of these drugs target fibrin (one of the main constituent of blood clots) and are therefore called fibrinolytics. These drugs are either derived from Streptococcus species, or, more recently, using recombinant biotechnology whereby tPA is manufactured using cell culture, resulting in a recombinant tissue plasminogen activator or rtPA.
Some fibrinolytics are:
- Streptokinase (Kabikinase)
- Anistreplase (Eminase)
- Recombinant tissue plasminogen activators (rtPA)
In people who receive thrombolytic therapy delivered through a catheter, there is a risk of hemorrhage as a side effect. Scientists have studied whether measuring fibrinogen in blood can be used as a biomarker to predict hemorrhage. As of 2017 it was not known if this works or not.
- TIMI – thrombolysis in myocardial infarction
- "Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients. Fibrinolytic Therapy Trialists' (FTT) Collaborative Group". Lancet. 343 (8893): 311–22. 5 February 1994. doi:10.1016/s0140-6736(94)91161-4. PMID 7905143.
- Wardlaw JM, Murray V, Berge E, Del Zoppo GJ (2014). "Thrombolysis for acute ischaemic stroke". Cochrane Database Syst Rev (7): CD000213. doi:10.1002/14651858.CD000213.pub3. PMC 4153726. PMID 25072528.
- Wechsler LR (2011). "Intravenous thrombolytic therapy for acute ischemic stroke". N Engl J Med. 364 (22): 2138–46. doi:10.1056/NEJMct1007370. PMID 21631326.
- Mistry EA (2017). "Mechanical Thrombectomy Outcomes With and Without Intravenous Thrombolysis in Stroke Patients: A Meta-Analysis". Stroke. 48 (9): 2450–2456. doi:10.1161/STROKEAHA.117.017320. PMID 28747462.
- Kuo WT1, Gould MK, Louie JD, Rosenberg JK, Sze DY, Hofmann LV. Catheter-directed therapy for the treatment of massive pulmonary embolism: systematic review and meta-analysis of modern techniques. J Vasc Interv Radiol. 2009 Nov;20(11):1431-40. doi: 10.1016/j.jvir.2009.08.002. PMID 19875060.
- Catanese L, Tarsia J, Fisher M (Feb 3, 2017). "Acute Ischemic Stroke Therapy Overview". Circ Res. 120 (3): 541–558. doi:10.1161/CIRCRESAHA.116.309278. PMID 28154103.
- Harvey D. White; Frans J. J. Van de Werf (1998). "Clinical Cardiology: New Frontiers Thrombolysis for Acute Myocardial Infarction". Circulation. 97 (16): 1632–1646. doi:10.1161/01.CIR.97.16.1632. PMID 9593569.
- Department of Health, Western Australia. "Protocol for Administering Alteplase in Acute Ischaemic Stroke Guidelines" (PDF). Perth: Health Networks Branch, Department of Health, Western Australia. Retrieved 2013-06-12.
- Jason Thurman; Edward C. Jauch (2002). "Acute ischemic stroke: emergent evaluation and management". Emergency Medicine Clinics of North America. 20 (3): 609–630. doi:10.1016/s0733-8627(02)00014-7.
- "Therapeutic Biologic Applications (BLA) > Difficulties in Obtaining Sufficient Amounts of Urokinase (Abbokinase)". US Food and Drug Administration. 10/07/2016. Retrieved 2016-12-28. Check date values in:
- "Therapeutic Biologics Applications (BLA)". US Food and Drug Administration. 07-10- 2016. Retrieved 2016-12-28. Check date values in:
- Poorthuis, Michiel H. F.; Brand, Eelco C.; Hazenberg, Constantijn E. V. B.; Schutgens, Roger E. G.; Westerink, Jan; Moll, Frans L.; de Borst, Gert J. (2017-03-05). "Plasma fibrinogen level as a potential predictor of hemorrhagic complications after catheter-directed thrombolysis for peripheral arterial occlusions". Journal of Vascular Surgery. 65 (5): 1519–1527.e26. doi:10.1016/j.jvs.2016.11.025. ISSN 1097-6809. PMID 28274749.