Make thick my blood, stop up th'access . . .
- Lady Macbeth, Macbeth
A man comes to see me regularly, and the same conversation always ensues. "How much rat poison will I take this month?" he says, to which I always reply, "that depends on how thin your blood is". This seemingly surreal conversation actually makes sense, as will be seen later.
Blood flows through the circulatory system, starting with the heart, which pumps blood along arteries to the vital organs and periphery. Having delivered oxygen and other nutrients, the oxygen-depleted blood travels along veins to the lungs to pick up more oxygen, and then returns to the heart where the process continues. In the healthy circulation, a delicate balance exists whereby blood flows when appropriate and coagulates when necessary.
Haemorrhage, the leakage of blood outside the circulatory system, is abnormal with one exception - the physiological bleeding during menstruation, when the lining of the womb is shed each month in the absence of pregnancy.
Blood has a very efficient in-built mechanism to stop bleeding. When you bleed following a cut, for instance, there is initially a brisk blood flow followed by a coagulation process which stops the bleeding by clot formation.
It is the absence of one or more of these clotting factors which causes haemophilia and other clotting disorders, which can cause damage through internal bleeding into joints and other structures. Potentially the most serious internal bleeding is into the brain, which can be disabling and often fatal.
Conversely, thrombosis (clot formation within the circulation) is always abnormal and can be dangerous. This can come about when clots develop in pre-existing diseased narrowed arteries, as in coronary and peripheral arterial disease. This can lead to death of heart tissue ("heart attack") and gangrene of extremities. It can also occur when there is sluggish flow within the veins after prolonged immobility, such as after surgery and, as recently described, after long air journeys in cramped conditions.
Smoking and certain medicines, such as the older generation of contraceptive pills, can also slightly increase the tendency to thrombosis.
A serious complication of thrombosis is embolism, when a piece of a thrombus breaks off and can travel to another part of the body causing further damage. Conditions such as a trial fibrillation (AF), in which one of the upper chambers of the heart beats irregularly and inefficiently, and deep vein thrombosis (DVT) in the calves are common sources of embolism. Emboli can also detach from diseased or artificial heart valves and arterial grafts. Pulmonary embolism, when an embolus blocks the main arteries in the lungs, is a common cause of sudden post-operative death.
Patients at risk of embolism from recurrent DVT, AF and other conditions causing excessive coagulation can benefit from having their blood made less likely to coagulate, but not to such an extent that even a small haemorrhage could be life-threatening. This is where the rat poison comes in.
Farmers and gardeners are familiar with warfarin, an anti-coagulant which kills rodents by causing massive internal bleeding. Warfarin is used in much smaller doses in humans to reduce the chances of further clot and embolus formation.
The effect of warfarin is measured by comparing a patient's coagulation ability to a standard normal value known as the International Normalisation Ratio (INR). Depending on the laboratory and individual condition, the INR should be between 2 and 4.5 for maximum efficacy. Below this range, anticoagulation is insufficient; above it, there is risk of haemorrhage.
If the INR is outside this range, warfarin dosage is adjusted accordingly. Most people take between one and five milligrams daily, but higher doses are not uncommon.
Warfarin's effect can be enhanced by other drugs, such as aspirin and alcohol, and it can be difficult to maintain the INR within the acceptable range. This is why monthly and even fortnightly INR testing is essential.
Blood for INR must be tested fairly quickly, otherwise the result may be inaccurate. This causes difficulties in rural practice where laboratory access is not close. In some parts of the west of Ireland, patients may have to travel over 50 miles to a hospital laboratory to have blood taken, a procedure which takes 30 seconds to do.
A recent pilot study by Dr Martin Daly of Ballygar, Co Galway, for the Western Health Board and NUI Galway, using near-patient testing (i.e. analysing the blood sample immediately in the surgery, using machines similar to glucometers familiar to diabetics), showed that warfarin adjustment can be made instantly, accurately and safely, with greater satisfaction and convenience for doctor and patient. The results were validated as accurate when compared to simultaneous standard laboratory testing of the same samples.
Running coagulation screening properly in general practice has implications for manpower, cost and maintenance of equipment, as well as protected time and infrastructure, if it is to work successfully. With more and more elderly patients returning from hospital on warfarin, this is a problem which will not go away.