Thrombolysis is the breakdown (lysis) of blood clots formed in blood vessels, using medication. It is used in ST elevation myocardial infarction, stroke, and very large pulmonary embolisms.
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.
Contents
1Medical uses
2Contraindications
2.1Myocardial infarction
2.2Stroke
3Side-effects
4Agents
5Research
6See also
7References
Medical uses
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.[1] 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.[2][3][4]
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.[5]
Severe deep vein thrombosis
Acute limb ischaemia
Apart from streptokinase, all thrombolytic drugs are administered together with heparin (unfractionated or low molecular weight heparin), usually for 24 to 48 hours.[citation needed]
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).[6]
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.
Contraindications
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.
Myocardial infarction
Absolute contraindications[7]
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
Relative contraindications[7]
Oral anticoagulant therapy
Acute pancreatitis
Pregnancy or within 1 week postpartum
Active peptic ulceration
Transient ischemic attack within 6 months
Dementia
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
Stroke
Absolute contraindications:[8]
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.
Relative contraindications:[9]
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
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.
Side-effects
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.
Agents
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)[10]
Anistreplase (Eminase)[10]
Recombinant tissue plasminogen activators (rtPA)
Alteplase (Activase or Actilyse)[10]
Reteplase (Retavase)[11]
Tenecteplase[11]
Research
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.[12]
See also
TIMI – thrombolysis in myocardial infarction
References
^"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.
^ abHarvey 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.
^ abc"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: |date= (help)
^ ab"Therapeutic Biologics Applications (BLA)". US Food and Drug Administration. 07-10- 2016. Retrieved 2016-12-28. Check date values in: |date= (help)
^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.
v
t
e
Proteins involved in coagulation
Coagulation factors
Primary hemostasis
vWF
platelet membrane glycoproteins: Ib (A
B
IX)
IIb/IIIa (IIb
IIIa)
VI
Intrinsic pathway
HMWK/Bradykinin
Prekallikrein/Kallikrein
XII "Hageman"
XI
IX
VIII
Extrinsic pathway
III "Tissue factor"
VII
Common pathway
X
V
II "(Pro)thrombin"
I "Fibrin"
Fibrinogen (FGA, FGG)
XIII
Coagulation inhibitors
Antithrombin (inhibits II, IX, X, XI, XII)
Protein C (inhibits V, VIII)/Protein S (cofactor for protein C)
Protein Z (inhibits X)
ZPI (inhibits X, XI)
TFPI (inhibits III)
Thrombolysis/fibrinolysis
Plasmin
tPA/urokinase
PAI-1/2
α2-AP
α2-macroglobulin
TAFI
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4. 急性ST上昇型心筋梗塞の血栓溶解療法：治療開始 fibrinolysis for acute st elevation myocardial infarction initiation of therapy
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English Journal
Recent advances in the management of pulmonary embolism: focus on the critically ill patients.
Annals of intensive care.Ann Intensive Care.2016 Dec;6(1):19. doi: 10.1186/s13613-016-0122-z. Epub 2016 Mar 3.
The aim of this narrative review is to summarize for intensivists or any physicians managing "severe" pulmonary embolism (PE) the main recent advances or recommendations in the care of patients including risk stratification, diagnostic algorithm, hemodynamic management in the intensive care unit (IC
Journal of enzyme inhibition and medicinal chemistry.J Enzyme Inhib Med Chem.2016 Dec;31(6):1411-4. doi: 10.3109/14756366.2016.1142985. Epub 2016 Feb 12.
The aim of this research is to evaluate the current streptokinase thrombolytic treatment and to identify or improve new techniques that will base new approaches with a higher efficiency in this area of expertise. In order to be as realistic as possible a new method was set up using magnetic vectoriz
INTRODUCTION: Acute ischemic stroke (AIS) represents a major cause of death and disability all over the world. The recommended therapy aims at dissolving the clot to re-establish quickly the blood flow to the brain and reduce neuronal injury. Intravenous administration of recombinant tissue-type pla
