Will Factor-2 mutation with clotting factor aid miscarriage?

Question

Hi doctor,

I am a 43-year-old female with a history of four recent miscarriages in the past 11 months, two chemical pregnancies, one blighted ovum, and one miscarriage at 7.5 weeks after a heartbeat was not seen at the second ultrasound. I recently discovered I am heterozygous for the Factor-2 mutation, and the fertility doctor advised me to go on Lovenox if I become pregnant again. I have recently discovered the following clotting factors as attached above. My question is how likely these types of clotting factors could potentially be related to repeated pregnancy loss. I have no history of clots but did have an elevated D-dimer and symptoms related to a potential PE. However, the CT scan was negative three years ago. I have two healthy daughters that are 17 and 13 years old. My fertility specialist has not received the clotting factor report that is attached to this email. How dangerous is a pregnancy, given the history of losses and so many clotting factors? Which ones are most concerning to you? Kindly give your opinion.

Answer 1

Hello,

Welcome to icliniq.com.

I understand your concern.

Clotting factors 1 to 13 are normally present in our body to aid in clotting and bleeding mechanisms in case of injury. The genes that code for these proteins are inherited from both parents, and any mutation in this will lead to changes in the clotting mechanism. According to your reports (attachments removed to protect the patient's identity), you have three mutations (highlighted in white), out of which Factor 2 mutations are the ones causing your symptoms. Factor 2 mutation (prothrombin gene mutation) is seen in 2 to 4% of the Caucasian population. Most people with prothrombin mutations will never develop an abnormal blood clot. But women who are pregnant already have a higher risk of getting a clot during and right after pregnancy (pregnancy is a hypercoagulation state; this is a normal physiological change in pregnancy). If a pregnant woman also has a prothrombin mutation, she will have a higher risk of blood clots.

When a blood clot forms inside a blood vessel like an artery or a vein, it can be dangerous. The clot can break off and travel through the blood into an artery in the lungs, heart, brain, or other organs. It can also cause a miscarriage, stillbirth, and other pregnancy complications. And in some cases, blood clots can be fatal. Apart from blood clots, prothrombin mutations are associated with an increased risk of complications during pregnancy. These complications include:

1) Pregnancy loss (miscarriage or stillbirth).

2) Preeclampsia (increased blood pressure and protein in the urine during pregnancy).

3) Slow fetal growth.

4) Placental abruption (early separation of the placenta from the uterine wall).

However, it is important to note that most women with prothrombin gene mutations have normal pregnancies when adequate precautions are taken. Hence, your doctor has advised you to take Lovenox (Enoxaparin), an anticoagulant, which will prevent the formation of clots and counteract the actions of the mutation. Though the risks of clots in pregnancy and pregnancy loss are high with medication, it is manageable. So if you want to try to conceive, I recommend you consult your doctor before conception and start on appropriate medications. I hope this was helpful.

Answer 2

Hello,

Welcome to icliniq.com.

MTHFR (methylenetetrahydrofolate reductase) mutation causes homocysteinemia, where blood homocysteine levels are increased. This gene is required for the formation of folate, which is required to form blood cells and the normal functioning of nerves in our body. So in the presence of MTHFR mutation with folic acid deficiency, recurrent pregnancy loss can occur. Also, patients with this mutation are always prone to increased clot formation, increased chances of cardiovascular and thromboembolic diseases (specifically blood clots, stroke, embolism, and heart attacks), and mood disorders. The treatment for this is Folic Acid and Lovenox. So if you consider becoming pregnant, like before with the Factor 2 Mutation, this will also add to the risk of clot formation. I hope this was helpful.