When you’ve been trying to get pregnant, a miscarriage is a heartbreaking event.  One common cause of miscarriages is blood clots.   Looking at some genetic risk factors as you’re trying to conceive can guide your choices which may reduce the risk of a future miscarriage.

Miscarriages are more common than most people think.  As women get older, so does the miscarriage rate.

For women between 30-30 years, the miscarriage rate is 25%.  For women 40-44 years, that goes up to 50%.  The risk for women over 45 years increases to 95%.

Blood clots and Miscarriage

Thrombophilia is a general term for disorders that cause blood clots.  A potential cause of miscarriages are blood clots that form in the placenta, cutting off blood flow to the baby.

Genetic causes of thrombophilia can increase the risk to the mother of getting a blood clot, such as a deep vein thrombosis, during pregnancy.

Two main causes of blood clots in pregnancy are known:

1. Autoimmune causes such as antiphospholipid syndrome
2. Genetic mutations that are linked to clotting disorders

Let’s take a look at both of these in more detail.

Autoimmune Causes of Blood Clots

A research study from a hematology clinic detailed the causes of blood clot disorders from women referred to them by an obstetrician for recurrent miscarriages.  The study found that 60% of the patients had an autoimmune condition called antiphospholipid syndrome and the rest had various genetic-based causes of blood clots. (study)

Antiphospholipid syndrome (APS) is an autoimmune disorder in which the body is attacking itself, causing an increased risk of blood clots.  This can result in an increased risk of miscarriages, stillbirths, pre-eclampsia, and preterm births.  Other symptoms of APS can include headaches, rash, seizures, and dementia.

APS can be classified as either a primary or secondary antiphospholipid syndrome, with the secondary classification given when it occurs along with other autoimmune diseases such as lupus.

APS is diagnosed in people who have both antiphospholipid antibodies in their blood (detected with a blood test) and who also have either blood clots or pregnancy-related complications. The antiphospholipid antibodies are reacting against the phospholipids in the cell membrane and cause an interaction with the cascade of events necessary for blood clotting.

Studies on APS note that it is the most frequent acquired cause for recurrent miscarriages and pregnancy complications. (study)(study)

Genetic causes of blood clot disorders:

There are four different genes that are often investigated by physicians when faced with recurrent miscarriages.

• MTHFR
• Factor V
• Prothrombin
• PAI-1

Let’s take a look at each of these individually to explain how they increase the risk for miscarriage.

MTHFR – methyltetrahydrofolate reductase gene:

The MTHFR gene codes for an enzyme that converts folate from foods and synthetic folic acid from supplements (vitamin B9) into the active form (methylfolate) used by your body.

A change in this gene referred to as MTHFR C677T causes the enzyme to have a decrease in its function. If you carry two copies of the variant (homozygous), you have a 70% decrease in the enzyme function.  About 10 – 15% of women are homozygous for the variant, which is tied to an increase in blood clots and miscarriages. (study)(study)

Numerous studies show women homozygous for the C677T variant are at an increased risk of recurrent miscarriages. The studies don’t always agree on how much of an increase there is, though, and this may be dependent on how much folate women in the study normally eat. (study)(study)

Folate is very important for healthy pregnancies, and this is especially true if you carry the MTHFR C677T variant.

Foods high in folate include beef liver, avocados, asparagus, broccoli, avocado, brussels sprouts, and dark, leafy greens.

One study showed that there might be a significant benefit to taking methylfolate instead of folic acid for women with the MTHFR C677T variant. The study looked at women who had been dealing with infertility or recurrent miscarriages for four years, and the patients had all been previously using high doses of folic acid (5 mg).  Switching the women from the high dose folic acid to a 600 mcg methylfolate supplement showed very promising results with most couples conceiving either naturally or with IVF. The study concluded “The conventional use of large doses of folic acid (5 mg/day) has become obsolete. Regular doses of folic acid (100-200 μg) can be tolerated in the general population but should be abandoned in the presence of MTHFR mutations, as the biochemical/genetic background of the patient precludes a correct supply of 5-MTHF, the active compound.” (study)

If you have your results from genetic testing, such as through 23andMe, you can check to see if you carry the MTHFR C677T variant.

Check your genetic data for rs1801133:

• AA: two copies (homozygous) for the MTHFR C677T variant
• AG: one copy (heterozygous) for the MTHFR C677T variant
• GG: normal

This is one genetic variant for which “knowledge is power”. Knowing that you carry the variant can guide you to make the necessary dietary or supplement changes that are right for your body.

If you carry the variant, consider supplementing with 800 mcg of methylfolate.

Factor V Leiden – F5 gene:

Factor V is a protein that is important in your body’s ability to form blood clots.  The F5 gene codes for the factor V protein, which is mainly synthesized in the liver.

There is a mutation known as factor V Leiden that causes it to be too active, which causes increased clotting.

Factor V Leiden causes an increased risk for deep vein thrombosis, pulmonary embolism, and an increase in the risk for miscarriages.  (study)  The increase in the risk of miscarriage is found in women carrying either one or two copies of the mutation. (study)(study)

Factor V Leiden also increases the risk of pregnancy-related venous thromboembolism, a type of blood clot that can form in the veins in the leg or arm and then travel through the circulatory system. (study)

If you have your genetic results, you can check to see if you are likely to carry the factor V Leiden variant. Keep in mind that tests from companies like 23andMe are not clinically certified, so your doctor may want to run another genetic test just to be sure of the results.

Check your genetic data for rs6025:

• TT: two copies of factor V Leiden
• CT: one copy of factor V Leiden
• CC: normal

Natural remedies such as salmon, turmeric, ginger, cayenne pepper, and cinnamon can help reduce blood clotting.

Prothrombin – F2 gene:

Another genetic variant that has been tied to recurrent miscarriages is the F2 (prothrombin) mutation known as G20210A.

When the body needs to form a blood clot, the prothrombin protein is activated into thrombin, an enzyme which is what makes up the fibrin strands in a clot.

The G20210A mutation increases the production of prothrombin, thus increasing the risk of blood clots.

There have been many studies on the prothrombin mutation and the risk of recurrent miscarriages. A meta-analysis that combined the information from 37 case-controlled studies found that the miscarriage risk for women over age 29 was increased by 1.9X to 2.4X, depending on the population studied.  (study)

If you have your genetic data, you can check to see if you carry the G20210A mutation. It is referred to in some genetic data as rs1799963, but, in 23andMe data, you would need to look for i3002432.

Check your genetic data for rs1799963 or i3002432:

• AA: two copies of the G20210A mutation
• AG: one copy of the G20210A mutation
• GG: normal

PAI1 – plasminogen activator inhibitor 1, SERPINE1 gene:

While prothrombin and factor V are involved in the creation of clots, the ability to break down a clot at the right time is also vitally important.  PAI-1 is involved in the activation of plasminogen, which is what breaks down clots.

There is a fairly common variant of PAI-1 known as the 4G/5G variant that has been linked to an increase in the risk for atherosclerosis and strokes. (study)

The PAI1 variant is often included in genetic testing for women who have recurrent miscarriages. Some studies find that the 4G variant slightly increases the risk for miscarriage, but not all of the studies agree. (study)(study)(study) So this may be a genetic risk factor that is not quite as big a factor as the others listed above.

Check your genetic data for rs1799762:

• DD or -/-: two copies of 4G variant, some increase in risk of miscarriage
• DI or -/ G: one copy of 4G, one copy of 5G variant
• II or G/G: two copies of 5G variant

If you carry the 4G variant, there are several natural supplements that have been shown to help.

• EGCG, the polyphenol found in green tea, has been shown to decrease PAI-1 level. (study)
• Resveratrol, a polyphenol found abundantly in grapes, has also been shown to suppress PAI-1 levels. (study)
• If you are overweight, losing weight will also help decrease PAI-1 levels. (study)

Natural Options for Blood Thinners:

Mother nature provides several natural solutions for reducing blood clots.

If your medical practitioner doesn’t have you on a prescription blood thinner, here are some natural options to investigate.

One of the many great benefits of fish oil is that it is a natural anticoagulant. Try incorporating fish into your diet several days a week, or look for a high quality fish oil supplement that contains 400 mg of DHA. (study)  Limit your exposure to mercury in seafood. Consumer Reports tested mercury levels in fish and found that Alaska salmon, tilapia, sardines, scallops and shrimp are usually the lowest in mercury. Labdoor is a great resource for finding out the amount of mercury (and other contaminants) in fish oil supplements.

Cinnamon contains coumarin, a natural blood thinner.  The less expensive cinnamon, cassia cinnamon, has the highest amounts of coumarin in it. (study)

Green tea contains polyphenols that inhibit blood clots. Just drinking green tea probably won’t affect your blood clot risk much, but taking supplements that contain EGCG may reduce your clotting risk. (study)

Studies show that people with low vitamin D levels are at a higher risk of deep vein thrombosis. (study)(study)  Spending time outside in the sunshine is a great way to boost your vitamin D levels! Supplemental vitamin D3 is another great option, especially if your vitamin D levels are low on a blood test.  More about vitamin D here.

Eat more dark chocolate! The flavanols in the cocoa bean have been shown to have a similar effect to low-dose aspirin for preventing clotting. (study)(study)  Looking for a healthier alternative to a chocolate bar? Try some cocoa nibs, which are simply 100% cocoa.  Use cacao, instead of cocoa which is more processed.

Get moving! One risk factors for blood clots is simply lack of exercise. This doesn’t mean that you have to spend hours in the gym on intense workouts. Take a walk around the block each morning and evening. Park farther from work and walk for a few blocks. Make it a priority to move more during the day!

Although the risks of miscarriage are real, making the necessary lifestyle changes CAN reduce the likelihood of it happening.