Factor V Leiden and the Pill

The oral contraceptive was first introduced in the US in 1960. Within two years, over a million women in the US were taking the “pill” as a safe, effective form of contraception. The use snowballed, and hundreds of millions of women now use oral contraceptives. Some regard it as the most socially significant advance in modern medicine as it gave women reproductive freedom.

The first reports that the pill could be associated with thrombosis came to light as early as 1962. The drug company, G D Seattle, the manufacturer of an early contraceptive, received 132 reports of thrombosis with 11 fatal cases. An initial review stated no conclusive evidence of a link between the pill and thrombosis. This report led the FDA to issue a statement to reassure doctors that the “pill” was safe. It was several years before the true thrombosis risk from the pill became apparent. It was not until the book, A Doctor’s Case Against the Pill by Barbara Seaman was published that the general public became aware of the serious nature of the risks of taking the pill.

The high risk of thrombosis was due to the high oestrogen content in early oral contraceptives. When first introduced, the pill contained 100 to 175mcg of oestrogen. Newer forms of contraception only have 35mcg, and the risk of thrombosis is far lower.

Risk

In medicine, we tend to use two terms when discussing risk: relative and absolute. These terms can be confusing and, if misused, can be alarming.

Relative risk is best thought of as a comparison between two groups. For example, the relative risk of having a blood clot from taking the pill is about 4 to 5. That means that blood clots occur four or five times more frequently in women taking the pill than in those not taking the pill. However, this does not tell us exactly how many women get blood clots in each group. This is where you need the absolute risk.

The absolute risk tells us how many people are affected. For example, the incidence of blood clots in women in their twenties is about 1 in 10,000. That means that amongst 10,000 women, only one will have a blood clot in the next year. If these 10,000 women all took the pill, four or five would have a clot. Although we know the pill is associated with a risk of blood clots, the risk is very low.

Factor V Leiden – risk

People with Factor V Leiden (FVL) have an increased risk of having a blood clot. The risk is only for deep vein thrombosis (DVT) or pulmonary embolus (PE). The risk of heart disease or stroke is not higher in people with Factor V Leiden. Various studies have reported slightly different levels of risk. But, the consensus is that a person with Factor V Leiden is 5 to 7 times more likely to get a blood clot than somebody without the mutation.

Factor V Leiden and the Pill

As both the pill and Factor V Leiden increase the risk of thrombosis, there is a combined risk for women with FVL who take an oestrogen-containing contraceptive. A large study in the 1990s found that women with FVL taking the pill had a risk 27 times higher than women without FVL not taking the pill. Subsequent studies have quoted a rate as high as 35 times higher. Therefore the absolute risk for a woman in her twenties is 35 in 10,000 or around 1 in 300. Although this is significantly higher than the DVT or PE background rate, the incidence remains low. It means most women with FVL do not get blood clots on the pill. The incidence is higher in older women as the background rate of clots in the 30 to 40yr age group is around 1 in 2000. Therefore a 35-year-old woman with FVL taking the pill has a risk of about 1 in 60.

Should we test all women before starting the pill?

The proposal to test all women before starting the pill has been discussed in the medical literature at some length. The current recommendation is not to test everyone. Why is this recommended practice?

There are several things to consider. The primary considerations are,

Will testing change practice?
Will testing cause any harm?
How much would screening cost?
Are resources available to provide testing?

Will testing change practice?

About 1 in 25 women will have a positive test. Should we advise all women with Factor V Leiden to avoid the pill? Remember, only 1 in 300 affected women will get a clot. The oestrogen-containing pill is the most effective form of contraception. Advising women to avoid the pill could lead to an increased rate of pregnancies. You might think this is unlikely, but previous pill scares have led to increased pregnancy rates.

In 1995 three reports were published in the Lancet suggesting that third-generation oral contraceptives had a higher risk of thrombosis than the second-generation pill. Immediately a significant number of women stopped taking the pill, and the pregnancy rate went up in several countries.

The current view is that women with no family history of venous thrombosis who have factor V Leiden can safely take an oestrogen-containing contraceptive. Therefore there is no reason to screen all women as the results will not change practice. Women with a family history of thrombosis should avoid oestrogen-containing contraceptives anyway, whether they have factor V Leiden or not.

Will testing cause harm?

The main concern is the psychological impact of labelling somebody with a condition that might carry some risk. Being told you have an inherited condition that increases your risk of thrombosis can be alarming, especially if you are not given appropriate counselling. But remember that only 1 in 2000 women with FVL at 20 will develop a blood clot. The vast majority of people with this condition will never have a clot. Once labelled with this condition, it will potentially impact your life. When you are pregnant or go for surgery, people will worry and may put you on treatment you do not need. There is a psychological burden knowing you have a medical condition; some people can handle the information without concern, but a significant amount of counselling is necessary for others. One of the primary diktats of medicine is: first, do no harm.

How much does screening cost and are there resources available?

Screening for Factor V Leiden costs approximately $100 per test. Some labs can offer it cheaper, and the price would most likely come down if mass screening was performed. But screening all young women in the country would have a considerable cost for the health service. The cost of testing, however, is only part of the picture. The major impact on resources is the time necessary to provide appropriate counselling. Ideally, all women should receive counselling before testing to understand the significance of the results. They would then require further counselling if they had a positive result. With the current shortage of GPs in New Zealand and many other countries, it may be impractical to implement a screening program.