Thrombolysis

Thrombolysis is the breakdown (lysis) of blood clots^[1] by pharmacological means, and commonly called clot busting. It works by stimulating secondary fibrinolysis by plasmin through infusion of analogs of tissue plasminogen activator (tPA), the protein that normally activates plasmin.

Medical uses

Diseases where thrombolysis is used:

• Myocardial infarction
• Stroke (ischemic stroke)^[2]
• Massive pulmonary embolism
• 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.

Thrombolysis is usually intravenous. It may also be used during an angiogram (intra-arterial thrombolysis), e.g. when patients present with stroke beyond three hours.

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. 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.

Contraindications

There are absolute and relative contraindications to thrombolysis.

Absolute

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, septic embolus.

Relative

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.

Agents

Thrombolysis mainly involves the use of thrombolytic drugs, which dissolve blood clots. These drugs 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:

• Streptokinase
• Urokinase
• Recombinant tissue plasminogen activators
  • Alteplase (tPA)
  • Reteplase
  • Tenecteplase

Principles

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) prevent 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.

References