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Thrombolysis is the breakdown (lysis) of blood clots by pharmacological means. It is colloquially referred to as clot busting for this reason. It works by stimulating fibrinolysis by plasmin through infusion of analogs of tissue plasminogen activator (tPA), the protein that normally activates plasmin.
Thrombolysis suggests the use of thrombolytic drugs, which are either derived from Streptococcus species, or, more recently, using recombinant biotechnology whereby tPA is manufactured by bacteria, resulting in a recombinant tissue plasminogen activator or rtPA.
Some commonly used thrombolytics are:
- Recombinant tissue plasminogen activators
Formation of blood clots lies at the basis of a number of serious diseases (see below). By breaking down the clot, the disease process can be arrested, or the complications reduced. While other anticoagulants (such as heparin) decrease the "growth" of a clot, thrombolytic agents actively reduce the size of the clot.
Most thrombolytic agents work by activating the enzyme plasminogen, which clears the cross-linked fibrin mesh (the backbone of a clot). This makes the clot soluble and subject to further proteolysis by other enzymes, and restores blood flow over occluded blood vessels.
A recent multicenter randomized trial (DUET) compared standard catheter-directed thrombolysis (CDT) versus ultrasound-accelerated thrombolysis (USAT, EKOS Corporation) for the treatment of acute peripheral arterial thrombotic occlusions. Results showed that, on average, patients treated with USAT were completed 12 hours sooner than those treated with standard CDT with no increase in "serious adverse events." Plans are underway to commence the DUET II study, which will be a non-randomized trial using the EKOS system with an even lower hourly drug dose with an expectation of further reducing bleeding complications.
Diseases where thrombolysis is used:
Thrombolysis is performed by many types of medical specialists, including interventional radiologists, vascular surgeons, cardiologists, interventional neuroradiologists, and neurosurgeons. In some settings 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. Emergency Care Practitioners exist in, among other countries, South Africa, United Kingdom, and New Zealand. Prehospital thrombolysis is always the result of a risk benefit calculation of the heart attack, thrombolysis risks, and PPCI availability. As such, the prehospital practitioner will often consult with the receiving cardiologist as to treatment decisions—many cardiologists have personal preferences to available treatment options.
There are absolute and relative contraindications to thrombolytic therapy.
Previous intracranial bleeding at any time, stroke in less than 6 months, closed head or facial trauma within 3 months, suspected aortic dissection, ischemic stroke within 3 months (except in ischemic stroke within 3 hours time), active bleeding diathesis, uncontrolled high blood pressure (>180 systolic or >100 diastolic), known structural cerebral vascular lesion, arterio-venous malformations, thrombocytopenia, known coagulation disorders, aneurysm, brain tumors, pericardial effusion.
Current anticoagulant use, invasive or surgical procedure in the last 2 weeks, prolonged cardiopulmonary resuscitation (CPR) defined as more than 10 minutes, known bleeding diathesis, pregnancy, hemorrhagic or diabetic retinopathies, active peptic ulcer, controlled severe hypertension.
- "thrombolysis" at Dorland's Medical Dictionary
- Schrijver, AM; et al (2011). "Dutch randomized trial comparing standard catheter-directed thrombolysis versus ultrasound-accelerated thrombolysis for thromboembolic infrainguinal disease (DUET): design and rationale". Trials. doi:10.1186/1745-6215-12-20. PMID 21255459.
- Randomized Controlled Multi-Center Trial Demonstrates Reduced Treatment Time and Drug Dose with EKOS vs. Catheter-Directed Thrombolysis in Peripheral Arterial Occlusions, EKOS Corporation/Bothell, WA. www.ekoscorp.com (April 15, 2013). Retrieved on April 19, 2013.
- Wardlaw JM, Zoppo G, Yamaguchi T, Berge E (2003). "Thrombolysis for acute ischaemic stroke". In Wardlaw, Joanna M. Cochrane database of systematic reviews (Online) (3): CD000213. doi:10.1002/14651858.CD000213. PMID 12917889.