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Medicine and Health

Does your blood clot too fast or too slow?

Historical diagrams of thrombosis
Source: J Cruveilhier, Anatomie pathologique du corps humain. vol 3. Paris (1842)

Thrombosis, a blood clotting condition, can be controlled with drugs that are taken orally. To make sure that they are safe and effective, much testing must be performed and the results must be comparable to World Health Organisation regulations. Reference materials are needed to aid laboratories in converting their measurements into results which can be compared internationally, regardless of which test reagents are used.


Thrombosis is a medical condition where blood starts to clot in blood vessels and organs. The word thrombosis comes from the Greek word for "curdling" and the problem affects thousands of people across Europe. However, it can be treated with drugs called anticoagulants. Some of these are taken orally and they work by interfering with the liver's production of the proteins which cause blood to clot. The treatment must not, however, stop the blood from clotting altogether. This would mean that patients may have trouble with internal bleeding. If they were, for example, to cut themselves or have an operation whilst taking the medicine, external bleeding may also cause problems. Clearly, this is undesirable.

To make sure that the anticoagulants strike the right balance with blood clotting, standardised laboratory tests are required. It is essential to have a universal scale to compare the effects of different anticoagulants and test systems between laboratories and countries.

Testing blood clotting times

Tests to measure the time it takes for blood to clot are performed on blood from patients taking the anticoagulants. These tests are called "prothrombin time" (PT) tests. In the test, a substance called thromboplastin is used. It is obtained in extracts from animal or human tissues. Test results for a given patient's specimen may vary depending on where the thromboplastin comes from. The PT test results will differ if the thromboplastin comes from an animal rather than a human, for instance.

Relating the results to WHO standards

A reference thromboplastin has been developed and produced, on a large-scale, to calibrate the different thromboplastins used by laboratories. The reagents will vary depending on how they are made and who the commercial supplier is. Through using this material, any PT results can be converted into a globally-accepted scale called the "International Normalised Ratio" or INR. The INR is defined as the prolongation factor of the clotting time which would be obtained if the original World Health Organisation (WHO) reference preparation was used. The potency of different anticoagulants can then be readily compared, in terms of INR. If these tests are accurate, the efficacy and safety of oral anticoagulants can be improved.

A reference material was produced several years ago for this purpose. Before the supplies were exhausted, a project began to produce another batch.

This reference material was made at the Thame Thrombosis and Haemostasis Research Foundation in the UK. The large batch of thromboplastin was extracted and prepared from rabbit brains; 10 000 ampoules were prepared and the thromboplastin was freeze-dried for preservation. Eleven laboratories took part in making the necessary measurements to make sure that the certified value for the thromboplastin was correct. Each of them used it to test blood plasma samples from twenty healthy volunteers and sixty patients on long-term oral anticoagulant treatment. Each blood specimen was tested both using the newly developed reference material and using the WHO's international reference preparation. This way, the results obtained for calibration using the new reference material could be correlated directly to the INR.

Networking thrombosis experts

The project partners had to collaborate closely to develop the material and perform the necessary measurements to ensure that the thromboplastin certified values were accurate. They are all either institutions treating thrombosis patients or national centres for research into blood coagulation. Many of them had worked on previous projects together and because many technical meetings were held to discuss results, this project reinforced the links of a European network of organisations interested in standardising anticoagulation treatment.

Ultimately, results from any blood testing laboratory should be comparable when this reference material is used. The objective is to harmonise the most important coagulation tests. It is vital that the test results used for diagnosis and the treatment of thrombosis be comparable independently of testing laboratory.



Project Title:  The Certification of the Third Reference Material for Rabbit Thromboplastin for Blood Coagulation Testing

Programmes: Standards, Measurements and Testing
Contract Reference:  

Cordis DatabaseFor more information on this project,
go to the Cordis Database Record