Rat poison to be replaced?

20 Jul

Warfarin has been used to thin the blood to decrease the tendency for thrombosis or as secondary prophylaxis (prevention of further episodes) in those individuals that have already formed a blood clot (thrombus) since I was born – for many years.
As GP’s we are now committed and compelled to take part in clinical-led commissioning and I shall be referring examples of this frequently.
Clinically-led commissioning is a continual process of analysing the needs of a community, designing pathways of care, then specifying and procuring services that will deliver and improve agreed health and social outcomes, within the resources available.
One such example is the provision of anticoagulation therapy services and for many months in Ealing Central Commissioning Group (ECCG) have been reviewing
how anticoagulation therapy is currently initiated including looking at recommendations for the new oral anticoagulants (noac) dabigatran, rivaroxaban and apixaban and the anticipated reduction in need for vitamin K antagonist monitoring services (INR monitoring).

You may be aware that anyone who takes warfarin must be monitored on a regular basis by blood test(INR) which until recently involved regular visits to the hospital to attend a clinic. As part of the commissioning we have taken over the monitoring of INR in general practise. But due to the complexity of initiating and stabilising treatment commissioning has been a long involved process to assure generalised commitment, safe practise and most of all taking into account the full cross section of patients needing this treatment.
The discovery of warfarin was centered in Canada and the United States1. In the early part of the 20th century, farmers in the northern prairie states of Canada and the USA began planting sweet clover plants imported from Europe. Although the sweet clover proved to be nutritious when used as fodder, it also brought a fatal disease which decimated cattle herds and horrified farmers: sweet clover disease, in which affected cattle developed relentless, spontaneous bleeding. Schofield, a veterinary pathologist in Alberta, reported in 1921 that the disease was caused by consumption of spoilt sweet clover hay. The fresh plant was known to contain the compound coumarin, which was not pathogenic. The mystery of why spoilt hay caused the disease was solved by Karl Paul Link and his co-workers in 1940 : in mouldy hay, coumarin is oxidised to 4-hydroxycoumarin and then coupled with formaldehyde and another coumarin moiety to form dicoumarol, an anticoagulant. This was responsible for the disease. Dicoumarol was patented in 1941 and was therapeutically used as an anticoagulant.
In 1951, a navy recruit unsuccessfully attempted suicide with 567 mg of warfarin. His surprising full recovery induced research into the anticoagulant potency of warfarin in humans. It was found to be far superior to dicoumarol. Clinicians quickly discarded dicoumarol in favour of “rat poison” warfarin : it was introduced commercially in 1954. In that same year, President Eisenhower was treated with warfarin following a heart attack.
As an aside I remember several years ago a delightful 98year old lady appearing in surgery asking to register provided she was not too old. She had been the Professor of Agriculture of Warsaw ( and honorary Professor at Glasgow)and believe or not in the waiting room at the same time she rediscovered an old student ( at that time 88yrs) a patient well known to me and he had been a farrier and a reputable breeder of Welsh mountain Ponies in South Wales before retiring to Ealing. It turned out that she had introduced sweet clover to Poland!

Warfarin is used used by more than 75,000 patients for short term or long term use and not only is it cheap at 2p a tablet but its anticoagulant effect is well tried and tested and its effect can be easily reversed in the event of gastro-intestinal bleeding or need of surgery. The anticoagulant level is easily measured. However, warfarin is slow to take effect and stabilise; constant monitoring is necessary as there is significant interaction with alcohol and some medication, food stuffs commonly leafy vegetables and cranberry juice and all foods containing Vitamin K and should be taken carefully
diet sheet

Patients must be totally compliant and maintain a record of INR readings(the yellow book)image
there is a risk of bleeding but someone would have to fall 200 times to have significant blood loss ie from bruising.
Recently a new class of drugs have been released and Rivaroxaban will be the drug of choice in Ealing- this decision has been met after consultation with our local consultant cardiologists, who we meet with in the surgery or at joint meetings. At present it will only be used in those patients who may need to be travelling frequently, with a uncontrolled INR, adverse effect with Warfarin or those who have had a stroke whilst taking Warfarin. As it is a new drug careful monitoring needs to take place and trials carried out to support a more widespread use.


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