Michael J. Paidas, M.D.
Associate Professor
Co-Director, Yale Women and Children’s Center for Blood Disorders
Pregnancy and Coagulation (Blood Clotting)
Pregnancy poses unique challenges to the blood clotting equilibrium in humans, probably more than in any other species. In order to orchestrate a healthy and clot free pregnancy, the body must achieve just the right balance between bleeding and clotting. In the beginning of pregnancy, preventing maternal bleeding and loss of the pregnancy is of prime importance. Closer to birth, the body prepares to prevent against the major risk for pregnant women: too much bleeding during childbirth. As part of this preparation, clotting factors increase during pregnancy, and protein S—a factor regulating clot breakdown—decreases. In addition, the effects of the pregnancy hormones, especially progesterone, cause blood vessels to dilate, creating a situation in which the blood pools, particularly in the legs. All of these changes place a pregnant woman at increased risk for thromboembolism (a blood clot).
How common are blood clots during pregnancy?
The risk of developing a blood clot is higher during pregnancy, delivery, and the 6-12 week period after birth. The chance of developing a blood clot is about 4-6 times more likely in pregnant women compared to non-pregnant women who are the same age. A blood clot occurs only in about one pregnant woman in 1,000-1,500. Blood clots remain a leading cause of maternal death in all parts of the world, and account for 11% of maternal deaths in the U.S.
What types of blood clots occur?
Deep vein thrombosis (DVT), a blood clot that occurs in the deep veins, usually in one leg, accounts for about 75% of all blood clots that happen during or right after pregnancy. An embolism happens when a blood clot in the leg travels to the lungs, and pulmonary embolism (PE) accounts for about 25% of blood clots in pregnancy. PE is likely to be fatal than DVT.
When in pregnancy is a woman most at risk?
DVT and PE may occur during pregnancy or up to 12 weeks after birth.
Are there certain factors that put women at greater risk to develop a blood clot related to pregnancy?
The most common risk factors for PE in the postpartum period are Cesarean delivery and obesity. Given the steadily increasing use of Cesarean section as a delivery choice (currently done in about three out of every 10 women), coupled with the obesity epidemic, the risk of having a blood clot related to pregnancy is rising in the United States. Scholars have highlighted the blood clotting risk associated with maternal obesity and recommended that obesity be managed in an effort to prevent thromboembolism (Duhl A, Paidas MJ et al. Am J Obstet Gynecol 2007).
Inherited thrombophilic conditions may also predispose women to develop blood clots in pregnancy. Understanding of thrombophilias (predisposition to clotting) and their impact on pregnancy continues to advance. As is often the case in medical research, initial small studies tend to magnify the impact of inherited risk factors for clotting, while further research either contradicted the initial findings or showed a weaker risk. For example, a case control study published in the New England Journal of Medicine (Gerhardt, 2000) compared the frequency of common thrombophilic conditions (factor V Leiden, prothrombin gene mutation, antithrombin deficiency and protein C deficiency) in two groups of pregnant women: one group of women who developed blood clots with or after pregnancy, and another group who were clot free.
The study found that the pregnant women who developed clots had significantly higher rates of the inherited thrombophilic conditions. In fact, factor V Leiden alone was found in more than 2 out of every 5 women with clots, as compared to fewer than 1 in 10 women who did not have any clots. However, when a large prospective (looking forward in time) study was performed on almost 5,000 women across the United States, the findings were different.
This study found that among women with no history of blood clots, having factor V Leiden was not found to be associated with clotting in pregnancy (Dizon Townson D, et al, Obstet Gynecol 2005). Because of these inconsistent results, it is difficult to analyze or conclude what the true risk is of developing a blood clot in pregnancy when a woman has an inherited thrombophilia. At this time, typically quoted risk estimates for thromboembolism in pregnancy consist of 0.2% for heterozygous factor V Leiden and 0.5% for heterozygous prothrombin gene mutation.
Does thrombophilia pose other risks to the pregnancy?
The strongest link between thrombophilia and pregnancy complications is women with antiphospholipid antibodies. Many studies have looked at the potential link between other thrombophilias and pregnancy complications, with mixed results. Thrombophilia might predispose a pregnant woman to complications associated with damage to the blood vessels of, or blood clots in, the placenta or recurrent pregnancy loss.
Are women who have thrombophilia managed differently during pregnancy?
Presently, if a pregnant patient has a thrombophilia and has had a blood clot prior to becoming pregnant, anticoagulation (i.e. use of a “blood thinning” medication) is recommended during and after pregnancy. Typically, low molecular weight heparin or heparin is the treatment of choice. In most ‘lower risk’ scenarios, low molecular weight heparin does not require any monitoring of blood levels.
However, with higher dosing to achieve greater levels of anticoagulation (therapeutic levels), monitoring of blood levels (factor Xa level) is usually performed, to ensure an adequate level of anticoagulation and prevent bleeding complications with “too high” levels.
If a woman does not have an identified thrombophilia, and her prior clotting event occurred because of a temporary risk factor, the risk of a repeat clot in pregnancy is low. In this case, only postpartum anticoagulation (with low molecular weight heparin, heparin or warfarin) is recommended.
The American Society of Hematology and other guidelines have proposed recommendations regarding the use of blood thinners to prevent a first venous thrombosis in the context of pregnancy and inherited thrombophilias, however there are sight differences in recommendations given the lack of high quality data to guide treatment approaches. There are recommended guidelines regarding the use of a blood thinner during pregnancy (antepartum) and/or in the postpartum period (after delivery).
What is the right dose of blood thinner to prevent VTE while pregnant?
A international trial in 2022 (Highlow study) evaluated two doses of low molecular weight heparin to prevent pregnancy associated recurrent VTE. This study included pregnant women with a prior history of an unexplained blood clot or a blood clot that happened in a setting of hormonal or minor risk factors. This study showed that standard low dose of low molecular weight heparin was the preferred preventative strategy to prevent recurrent blood clot in pregnant women with prior VTE.
