Patient Education Blog

Pregnancy Loss and Clotting Disorders

How common is pregnancy loss? What are the causes?

Pregnancy loss (= miscarriage) in the general population is common. Most losses occur in the first trimester. As many as 5 % of women have 2 or more early losses; 1-2 % have 3 or more early losses [ref 1]. Well established risk factors for pregnancy loss are: (a) advanced age of the mother, (b) anatomic abnormalities of the uterus (such as fibroids), (c) chromosome abnormalities of fetus, the mother or the father, (d) underlying diseases of the mother (endocrine, immunologic), (e) maternal hormonal unbalances.  The acquired clotting disorder called “antiphospholipid antibody syndrome” is also a risk factor for pregnancy loss. The role of inherited clotting disorders (= thrombophilias) contributing to pregnancy loss is less clear.

Are clotting disorders risk factors for pregnancy loss?

a)     Acquired Clotting Disorders: Repeatedly and clearly positive antiphospholipid antibodies (= APLA) are associated with pregnancy loss [ref 2]. APLA are proteins that are made by the body’s immune system. Often it is not clear why certain people make them. A person can make a variety of different APLA and there are a number of tests that can be done to test for them:

  1. Lupus anticoagulant
  2. anticardiolipin antibodies
  3. anti-beta-2-glycoprotein-I antibodies
  4. anti-phosphatidyl-serine antibodies
  5. anti-phosphatidyl-inositol antibodies
  6. anti-phosphatidyl-ethanolamine antibodies.

However, only the first three in the list above are well established risk factors for pregnancy loss [ref 2,3]. APLA have to be clearly elevated and repeatedly positive (preferably 3 or more months apart) before they are considered to be relevant / significant.

b)    Inherited Clotting Disorders
A number of inherited clotting disorders exist that put people at risk for blood clots, most commonly clots in the legs (deep vein thrombosis = DVT) and lung (pulmonary embolism = PE). In theory, these clotting disorders may also lead to blood clots in the placenta and, thus, decreased oxygen delivery to the unborn, and miscarriages. Investigators have, therefore, looked whether these clotting disorders are associated with pregnancy loss. And, indeed, some of them are: (a) Factor V Leiden and the prothrombin 20210 mutation are slight risk factors for pregnancy loss [ref 2]; (b) The 3 clotting disorders “Protein C, S, and antithrombin deficiency” are uncommon and, therefore, not enough data exist as to whether they increase the risk for pregnancy loss; (c) Some genetic variants in a gene called MTHFR (methylene-tetrahydrofolate reductase) was, in the past, thought to be a risk factor for blood clots and pregnancy loss. However, in recent years they have been found to neither cause clots nor pregnancy loss, and, therefore, should not be considered any more a clotting disorder [ref 4].

It is important to keep in mind that the risk for pregnancy loss in women with thrombophilia is low: the majority of women with thrombophilia will have a successful pregnancy [ref 5]. To summarize, the potentially relevant  inherited clotting disorders to be considered in pregnancy loss, are:

  1. Factor V Leiden
  2. Prothrombin 20210 mutation (also referred to as factor II mutation)
  3. Protein C deficiency
  4. Protein S deficiency
  5. Antithrombin deficiency

In women with pregnancy loss and thrombophilia, do “blood thinners” prevent future pregnancy losses?

a)     APLA: Treatment with heparin plus aspirin in women with a history of pregnancy losses who have APLA leads to a higher live birth rate in a subsequent pregnancy compared to no treatment. Therefore, heparin plus aspirin treatment is recommended in women with pregnancy loss associated with APLA [ref 2,7,8].

b)    Inherited Clotting Disorders: At present it is not known whether treatment with heparin and/or aspirin in women with a history of pregnancy losses and inherited thrombophilia leads to an increase in live birth rate in a subsequent pregnancy [ref 2]. The potential benefit of therapy – i.e. higher live birth rate – needs to be weighed against the potential downsides of treatment – i.e.  cost, inconvenience, discomfort, risk for bleeding, skin reactions, the complication called “heparin induced thrombocytopenia” or HIT, withholding of epidural anesthesia, induction of labor. An individual decision needs to be made in discussion with the woman.

c)     Women with pregnancy loss and no detectable thrombophilia: Data to this date show that there is no benefit of giving heparin and/or aspirin therapy to women with unexplained pregnancy loss who do not have a detectable clotting disorder.

 

Existing Professional Guidelines

1.  ACOG (Am College of Obstetricians and Gynecologists):  ACOG has published 2 relevant Practice Bulletins/ guidelines:

  • The ACOG Practice Bulletin in “Inherited Thrombophilias in Pregnancy” states that inherited thrombophilia testing in women who have experienced recurrent fetal loss is not recommended because it is unclear whether anticoagulation (blood thinning medication) reduces future losses [ref  6].
  • The ACOG Practice Bulletin on “Antiphospholipid Syndrome” states: (a) that testing for antiphospholipid antibodies is indicated in women with a history of one fetal loss after week 10 of pregnancy, of 3 or more recurrent early losses before week 10; and (b) that in women with antiphospholipid antibody syndrome and a history of stillbirth or recurrent pregnancy loss treatment with the “blood thinner” heparin and low-dose aspirin should be considered [ref  7].

2.  ASRM (American Society for Reproductive Medicine): A clinical practice guideline on recurrent pregnancy loss by the Practice Committee of the organization is in development. I have been told that completion and publication is anticipated sometime before the end of 2011.

3.  ACCP (American College of Chest Physicians: ACCP recommends to screen women with recurrent early pregnancy loss or unexplained lat loss for antiphospholipid antibodies and, if positive, treat during future pregnancy with heparin plus aspirin [ref 8, section 9.1.1.]. Given the uncertainty about the role of inherited thrombophilias in causing pregnancy loss and whether there is benefit treating women with thrombophilia and pregnancy loss with “blood thinners”, ACCP does not give any recommendations on this topic.

My Own Clinical Approach

What should the woman WITH pregnancy loss know?

  • One or more pregnancy losses are common in the general population.
  • The majority of women with 1, 2 or 3 pregnancy losses have a successful subsequent pregnancy WITHOUT any treatment.
  • The majority of pregnancy losses is not explained by clotting disorders, but is due to other causes.
  • The woman with 3 or more 1st trimester pregnancy losses or 1 or more losses after week 10 should be worked up for a variety of causes (chromosomal abnormalities, anatomic uterus abnormalities, endocrine disorders, hormonal abnormalities) before being defined as having “unexplained” pregnancy losses.
  • If the woman truly has recurrent early or one or more later UNEXPLAINED losses, thrombophilia work-up can be considered. Appropriate testing should/could be:
    • Lupus anticoagulant
    • anticardiolipin IgG and IgM antibodies
    • anti-beta-2-glycoprotein-I IgG and IgM antibodies
    • factor V Leiden
    • prothrombin 20210 mutation
    • protein C activity (also called functional protein C)
    • protein S activity (also called functional protein S)
    • antithrombin activity (also called functional antithrombin).
    • If one of these clotting disorders is clearly / unequivocally found, then discussion of heparin therapy with or without aspirin can be discussed, weighing all the risks and benefits of treatment.

What should the woman with a known thrombophilia, but WITHOUT a history of pregnancy loss know if she plans to get pregnant?

  • The majority of women who have a thrombophilia have uneventful pregnancies
  • Thrombophilias are only very mild risk factors for pregnancy loss.
  • A discussion should be held with the woman’s physician whether heparin therapy might be needed to prevent blood clots in the legs (deep vein thrombosis = DVT) or lung (pulmonary embolism = PE).
  • Barely ever is there an indication for therapy with “blood thinners” purely to prevent pregnancy loss.

 Support Forums

Clot Connect has a Support Forum, including one for “Women’s Health and Clotting“.  A number of other support forums for women with thrombophilia and pregnancy loss also exist on the internet.

References

  1. Rai R et al. Recurrent miscarriage. Lancet. 2006;368:601-611.
  2. Bates SM. Consultative hematology: the pregnant patient pregnancy loss.  Am Soc Hematol Educ Program.  2010;2010:166-172.
  3. Alijotas-Reig J et al. Anti-β2-glycoprotein-I and anti-phosphatidylserine antibodies in women with spontaneous pregnancy loss. Fertility and Sterility 2010;93:2330-2336.
  4. Rey E et al. Thrombophilic disorders and fetal loss: a meta-analysis. Lancet 2003 Mar 15;361(9361):901-8.
  5. Rodger MA et al. The association of factor V Leiden and prothrombin gene mutation and placenta-mediated pregnancy complications: a systematic review and meta-analysis of prospective cohort studies. PLoS Med. 2010 Jun 15;7(6):e1000292.
  6. Am College of Obstetricians and Gynecologists (ACOG) Practice Bulletin. Inherited thrombophilias and pregnancy. July 2010;number 113, page 1-11.
  7. Am College of Obstetricians and Gynecologists (ACOG) Practice Bulletin. Antiphospholipid Syndrome. Jan 2011;number 118, page 192-199.
  8. Bates SM et al. Venous thromboembolism, thrombophilia, antithrombotic therapy, and pregnancy: Amercian College of Chest Physicians evidence-based clinical practice guideline (8th edition). Chest. 2008 Jun;133(6 Suppl):844S-886S.

For Health Care Professionals:  This same information, written for health care professionals, can be found here.

Disclosure: I have no financial conflict of interest relevant to this educational post.

Last updated:  June 14th, 2011

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ClotConnect.org, its contributors, authors, advisors, members and affiliate organizations do not assume any liability for the content of the website, blog and educational materials. Medical information changes rapidly. While information is believed to be correct, no representation is made and no responsibility is assumed for the accuracy of information contained on or available through this web site and blog. Information is subject to change without notice. 

 

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8 Responses to “Pregnancy Loss and Clotting Disorders”

  1. Jennifer says:

    I have been browsing the internet hoping to find a site that has a forum or chat group for individuals who have protein c deficiency. Have you ever thought of extending for this group?

    • Stephan Moll says:

      Clot Connect has a Forum for any individual with a clotting disorder, including protein C deficiency. The Forum has a subgroup “Thrombophilia (clotting disorders)”. It is not specific for protein C deficiency, as many of the issues relevant for indivdiuals with protein C deficiency also apply to individuals with other clotting disorders. Also: Clot Connect recently started a discussion forum – http://forum.clotconnect.org – which has a group on “Women’s Health”. Please feel free to visit. Finally, there is a discussion of protien C deficiency at http://clotconnect.wordpress.com/2011/06/15/protein-c-deficiency.

    • Susan says:

      Hi Jennifer,

      Not sure if you are pregnant or trying to conceive (or neither), but there’s a helpful community group on Babycenter.com called “Lovely Lovenox Ladies”. Many of them, like me, have protein deficiencies, and they are a great resource. Good luck with everything.

      Susan

  2. Jo says:

    I was reading CNN — ‘When a Miscarriage isn’t a Fluke’ and found this site from there. I tried having a baby at 34 (USA). I had two miscarriages then a baby girl and then two more miscarriages and an ectopic pregnancy. By this time I was 40 and we gave up — but at 43 I became pregnant again. I was living in Australia and the doctor I saw looked at my miscarriage history and said I needed to take baby aspirin every day to stop possible blood clots forming and that was linked to reoccurring miscarriages. At 44 I had a perfect baby boy. I was never given a diagnoses so was interested to read this article and find this site — although sad that I didn’t know earlier.

  3. Sharon says:

    I was diagnosed with antiphospholipid antibody syndrome after having 2 miscarriages, and was put on baby aspirin at first, then a neonatologist switched me to heparin then lovenox. I carried that pregnancy to term, and my “baby” just turned 3 years old, happy and healthy. I REALLY had to push my doctors to do any kind of testing b/c of that 3 consecutive miscarriage rule. (This was a few years ago, before they rescinded that rule – I’m so glad they did!) I had 2 babies born healthy, so they felt that nothing could be wrong, but we had a strong family history of miscarriages within my siblings, and I felt very strongly that there was a reason. After a lot of pushiness on my part, one of my doctors listened and ran the tests. Kudos for having this story put out there! I think there is not enough awareness among doctors, and definitely among patients. Sometimes you have to follow your instincts and advocate for yourself (and baby) even when it is not well received. Thanks again for posting the story.

  4. hayley says:

    i lost my baby to a placenta abruption in march this year. i was put on clexane 60mg a day injection as my sister died of a pe ten years ago, so they put me on it as a percaution while i was pregnant, but i never had a clot before then. when i lost my baby in march the next month i got pe even tho i was still on the clexane injections, and then got told i carry a gene hetro somthing; but i was tested when my sister died and got told i was fine. how come ten years later i get the gene disorder and still got a pe even while on clexane. i did have a emergency section and was put under while they did the section. now am on warfarin and keep thinking am i to get more clots? my heads amess at the minute about all this and my anxietys through the roof. please can you help answer some of this as i dont understand.

    • Stephan Moll says:

      (a) Blood thinners (like the low molecular weight heparin Clexane) are quite effective in preventing clots, but not 100 % effective; (b) to understand the issue with the test results and the absence or presence of a heterozgyous mutation, you would need to know what tests were done. Ask your physicians to explain what was done and what it means.