Thrombolysis for Peripheral Vascular Disease

What is thrombolysis?

Thrombolysis is a treatment that uses naturally occurring enzymes to break up and dissolve blood clots that are blocking veins or arteries. It is only useful for arterial blockages they are causing significant problems by impeding blood flow to the tissues. In deep venous thrombosis it may also prevent the development of complications. 

What enzymes are used in thrombolysis?

Urokinase, streptokinase and tissue plasminogen activator (tPa) are the main enzymes in common use.

tPa is produced by the cells that line the blood vessels (vascular endothelial cells). tPa is resonsible for thrombolysis that occurs naturally in normal blood vessels (fibrinolysis). Urokinase is also a naturally occurring compound causing fibrinolysis, first discovered in urine, but present in many cells. Streptokinase is a substance that causes thrombolysis, but is not naturally occurring in man. It is produced by certain bacteria (streptococci).

Why is thrombolysis used?

Thrombolysis is used to break up blood clots when they are causing clinical problems.  Not all blood clots are dangerous.  Without blood clotting we would die from a minor cut, but clots that form in arteries taking blood and oxygen to vital organs can be dangerous and even fatal. Blood clots also form in veins that drain blood from the tissues back to the heart.

In principle thrombolysis can be used to unblock blood vessels anywhere in the body. For instance a blockage to an artery to the brain causing a stroke could be treated by thrombolysis and lessen the severity of a stroke. A blockage to an artery to the heart causing a heart attack can be treated by thrombolysis, lessening the effect of the heart attack and reopening the blocked artery to the heart. In the legs thrombolysis can be used to dissolve blood clots in arteries to the legs and also unblock arterial bypass grafts in the legs.

Thrombolysis can also be used to dissolve blood clots in the veins of the legs when a deep vein thrombosis occurs. This is especially useful when a clot or thrombosis takes place in a larger vein because it will assist with resolution of immediate symptoms but also potentially reduce the risk of long term complications from DVT.

The most common use for thrombolysis is in patients that have suffered heart attacks.

What are the different types of thrombolysis?

Apart from the different enzymes that can be used the method of administration can be altered depending on circumstances.

The most common method of administration is intravenous, that is into a vein, usually a visible vein in the arm.  It is the most simple method of administration. The disadvantage of this method is that the thrombolytic agent is not delivered directly to the blood clot, but circulates around the blood stream until some of the enzymes reach the blockage. This lessens the effect of the enzymes because of dilution, but makes the administration of the treatment much easier. It is the method most used to treat heart attacks. 

Intra-arterial administration, that is into an artery, usually means placing a fine catheter (tube) into an artery using xrays to guide placement of the catheter directly into the area where the blood clot is present. The enzymes can then be administered directly into the blood clot. This maximises the effect of the treatment but it is a much more complicated  procedure.

When used in patients with extensive deep venous thrombosis a catheter is placed into the deep vein and the clot treated directly. This usually acts rapidly and a combination of thrombolysis and mechanical disruption of the blood clot can be used.

Occasionally thrombolysis can be used during the course of an operation (intraoperative thrombolysis) to optimise the outcomes from the operation by opening up blocked veins or arteries.

When is thrombolysis useful?

Although there are many areas where thrombolysis could be useful it is definitely not appropriate for everyone and great care needs to be taken in selecting patients who will potentially benefit.  In general thrombolysis is most useful in fresh blood clot as this will dissolve most easily, although on exceptional occasions it can be used up to 8 weeks after clot has formed.

Thrombolysis is most useful in the treatment of heart attacks where it is given very frequently as an intravenous injection when the patient presents with a confirmed heart attack.  The benefit is greatest when the injection is given as soon as possible after the heart attack starts but always within the first hour. Although there is some benefit from thrombolysis in patients with strokes this is more limited and logistically more difficult as it is vital to confirm the stroke has not been caused by bleeding into the brain by performing a CT scan of the brain. This is because if thrombolysis is given and the stroke has been caused by bleeding, thrombolysis will worsen the stroke. In addition the brain is very sensitive and even a few minutes without oxygen can result in brain tissue that is damaged beyond repair.

In selected patients with blockages in the arteries of the legs (acute limb ischaemia) or blockages of bypass grafts in the legs thrombolysis can be used to restore blood flow to the leg and foot.

Are there any risks from thrombolysis?

Bleeding – The main risk attached to thrombolysis is the risk of bleeding. Usually if significant bleeding develops whilst being treated with thrombolysis then the treatment must be stopped.  Bleeding can occur from any puncture wounds on the skin that have been used to insert tubes into the arteries. Spontaneous bleeding can also develop. Sometimes more serious and even fatal bleeding can occur inside the brain (1% or 1 in 100 patients) . Major bleeding anywhere in the body can occur in up to 5% (1 in 20) patients.  More minor bleeding can develop in up to 15% of patients.

Reperfusion injury occurs when the arterial blood supply and hence oxygen supply to the tissues improves after the blockages in the arteries are opened up. Because the tissues have been altered by being starved of oxygen they respond differently when oxygen levels return to normal. Free radicals are produced which cause further damage to the tissues so that the original damage is made worse by improving the circulation.

Distal embolisation – occurs when bits of clot break off as they are being dissolved. The clots can be dislodged further down the arteries and cause further problems by preventing blood reaching the tissues. In the veins clots can break off and travel to the lungs causing pulmonary embolus. One way to prevent this is to place a metal filter into the larger veins to catch the clots before they reach the lungs.

Allergic reactions are a rare event but if they occur will require the thrombolysis to stop.

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