HomeColumnsEvidence MattersGenetic testing of patients with blood clots: No brainer or no point?

Genetic testing of patients with blood clots: No brainer or no point?

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We don’t often think about the delicate balance of our blood. On one hand, we need to be able to form blood clots if we injure ourselves so that we don’t lose too much blood. On the other hand, we need the blood not to clot so that it flows through our arteries and veins to bring oxygen and nutrients to all parts of our body. How does our blood form clots when it should, and not clot when it shouldn’t?

A clotting cascade – a series of chemical reactions between cells and proteins in our blood – is the key. Some of these proteins are clotting factors, chemicals that help our blood to form a clot when needed. Other proteins, called anti-clotting factors help to make sure we don’t form clots when we shouldn’t.

However, sometimes our blood fails to achieve this delicate balance and unnecessary clots form, often in the deep veins of the body, such as those found in our legs. This type of clot is known as a deep vein thrombosis or DVT. If a DVT breaks free, it can lodge in the small vessels of the lung, causing a pulmonary embolus (PE) – which can be life-threatening.

There are many reasons why a clot might form when it shouldn’t. These include trauma, surgery, immobilization (e.g., a long car trip), pregnancy, some medications, cancer, and other medical conditions. But some of us have gene mutations in our DNA that can affect the clotting factors in our blood. These mutations result in thrombophilia – a group of disorders, either inherited or acquired, that lead to an increased risk of DVT and PE.


The most common of these mutations, Factor V Leiden (FVL), affects the blood clotting protein factor V. In people with this mutation, their factor V doesn’t deactivate as quickly as it should which can lead to the formation of clots. We inherit one gene for factor V from our mother and one from our father. If we have one mutated gene for factor V that means we are heterozygous and our risk of forming a clot is increased, but not by a lot – people with no mutation have a risk of developing a DVT of about one in 1000, those who are heterozygous for the mutation have a DVT risk of about three to eight in a 1000. If both genes are mutated (homozygous), the clot risk is higher at about 80 in a thousand.

A second mutation can affect factor II, another important clotting factor which is also known as prothrombin. Again, people who are heterozygous for the mutation (only one mutated gene) have only a small increased risk of developing a blood clot – from one in a 1000 without the mutation to two or three in a 1000 with the mutation. If homozygous for a prothrombin mutation, the risk is increased further to about 20 in a 1000.

Commercial tests, that are highly accurate, are available in Canada to test for Factor V Leiden and prothrombin mutations. But whether these tests are useful to help guide management of patients with a DVT and to predict their risk of developing future clots is uncertain. This question is particularly important for patients who have developed a DVT but have no other known risk factors – and that accounts for around half of patients with a first DVT. Should we be testing these patients for Factor V Leiden and prothrombin mutations? Will it improve their care and their future health?

CADTH — an independent, evidence-based agency that finds and summarizes the research on drugs, medical devices, and procedures – recently looked at the evidence on testing for Factor V Leiden and prothrombin mutations in patients with a first, unexplained DVT. The review found that there was evidence that Factor V Leiden or prothrombin mutations are a risk factor for a first, unexplained PE but the rate of these mutations was the same in patients who had another identified risk factor for PE. The review also found that the chance of a DVT happening again after a first DVT seemed to be similar whether or not patients were tested for Factor V Leiden and prothrombin mutations. And the risk of recurrence was similar in patients who were found to be heterozygous for one of the mutations and for patients who tested negative for either mutation. No association was found between having Factor V Leiden or a prothrombin mutation and an increased risk of having a DVT recurrence.


Evidence-based guidelines state that having Factor V Leiden or a prothrombin mutation should not affect the treatment patients receive to avoid another DVT. In other words, the treatment recommendations are the same whether or not a mutation is present.

Testing for either of the mutations did not appear to have any major adverse effects, but increased worry is reported amongst patients who test positive for either mutation. People who test positive also tend to overestimate the risk of having another DVT. However, lifestyle choices to reduce DVT risk that may result from knowing about the mutation could potentially be beneficial, but evidence is lacking.

When CADTH’s expert committee reviewed the evidence gathered on Factor V Leiden and prothrombin mutation testing, they recommended not to routinely test patients who have had a first, unexplained DVT. The reasons for their recommendation were that testing positive for the mutations did not help to predict the risk of having another DVT, there was no evidence to show that testing improved patient health outcomes, and testing brings with it additional costs.

The availability of genetic testing for a variety of conditions raises many questions for patients and health care professionals about whether or not to test, and what to do with the testing results. Knowing what the evidence is on Factor V Leiden and prothrombin mutation testing in patients with a first, unexplained DVT is helpful to make informed choices about whether or not to test.

If you’d like more information about the CADTH project on Factor V Leiden and prothrombin mutation testing – or on a variety of other drugs, devices, or procedures – they are all freely available on the CADTH website: www.cadth.ca. To learn more about CADTH, visit www.cadth.ca, follow us on Twitter: @CADTH_ACMTS, or talk to our Liaison Officer in your region:



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