Thursday, February 12, 2009

Thrombophilias, miscarriage and bloodthinners - a research review

If you have suffered one or more miscarriages, and are trying to figure out whether or not you may need blood thinners (heparin or lovenox) next time you get pregnant, here is some data to ponder (and share with your doctor):

[Treatment with enoxaparin (“Lovenox”) adapted to the fertility programs in women with recurrent abortion and
Sarto A, Rocha M, Geller M, Capmany C, Martinez M, Quintans C, Donaldson M, Pasqualini RS.

Acquired and inherited thrombophilia are associated with recurrent pregnancy loss (RPL). Antithrombotic therapy could restore hemostatic balance and improve early placentation and gestational outcome. We evaluated the efficacy of enoxaparin adapted to the fertility program for prevention of pregnancy loss in 35 women (W) with early RPL and thrombophilia. Previous to the diagnosis of thrombophilia, they had had a total of 105 gestations of which 89 (85%) ended in early pregnancy loss. After diagnosis of thrombophilia, 35 subsequent pregnancies were treated with enoxaparin. In 5 cases assisted reproductive techniques were necessary to achieve pregnancy due to couple infertility. In 17 W who had had at least one preclinical pregnancy loss, enoxaparin (20 mg/d/s.c.) was started previous to conception and adapted to the fertility program. All the women continued with the gestational regime. Eighteen W with only clinical pregnancy loss started enoxaparin (20 mg twice per day s.c.) after biochemical pregnancy diagnosis. During gestations heparin dose was adjusted with anti Xa test, maintaining a range between 0.3 at 0.6 u/ml. With antithrombotic therapy, 30/35 (85%) of the pregnancies ended in live birth versus 16/105 (15%) of the pregnancies without treatment (p < 0.001).


American Journal Of Reproductive Immunology
Volume 49 Issue 2 Page 90 - February 2003

Successful Pregnancy with Low Molecular Weight Heparin in Two Women with Recurrent Miscarriage of Unknown Etiology

Yoshihiro Miyashita, Masako Waguri, Isao Nakanishi, Noriyuki Suehara, and Tomio Fujita

We report here two cases of recurrent miscarriages that were successfully treated with continuous intravenous administration of low molecular weight heparin (LMWH). One patient experienced 11 spontaneous abortions, and the other eight abortions. Previous treatments including prednisone, aspirin and mononuclear-cell immunization were all unsuccessful. They were negative for anticardiolipin antibodies and lupus anticoagulant, and had no inherited thrombophilic disorder. Intravenous administration of LMWH, 4800 units of dalteparin, was started as soon as the conception was confirmed, and was continued until 34 weeks of gestation. They were delivered of live born infants.


Clin Appl Thromb Hemost. 2005 Jan;11(1):1-13.
Recurrent miscarriage syndrome and infertility due to blood coagulation protein/platelet defects: a review and update.

Bick RL, Hoppensteadt D.

University of Texas Southwestern Medical Center, Dallas, Texas 75231, USA.

Three-hundred fifty-one women were referred for thrombosis and hemostasis evaluation after suffering recurrent miscarriages. All patients were referred by a high-risk obstetrician or reproductive medicine specialist after anatomic, hormonal or chromosomal defects had been ruled out. These patients were assessed over a three year period. The mean patient age at referral was 34 years and the mean number of miscarriages was 2.9 (2-9). All patients underwent a thorough evaluation for thrombophilia and, when indicated, a hemorrhagic disorder. Of the 351 patients, 29 (8%) had no defect. Of the remaining 322 patients, 7 (2%) had a bleeding disorder: 3 with platelet dysfunction, 1 with Factor XIII deficiency, 3 with von Willebrand's and 3 with Osler-Weber-Rendu. The remainder of the patients had a thrombophilia as follows: 195 (60%) had antiphospholipid syndrome, 64 (20%) had Sticky Platelet Syndrome, 38 (12%) had MTHFR mutation, 23 (7.1%) had PAI-1 polymorphism, 12 (3.7%) had Protein S deficiency, 12 (3.7%) had Factor V Leiden, 3 (1%), had AT deficiency, 3 (1%) had Heparin-Cofactor II deficiency, 3 (1%) had TPA deficiency, and 6 (2%) had Protein C deficiency. There were a total of 364 defects found in the 312 patients harboring thrombophilia; thus, several harbored two and a few harbored three separate defects. All patients with thrombophilia were treated with preconception ASA at 81 mg/day with the immediate post-conception addition of heparin or LMW heparin (Dalteparin). Both ASA and heparin/LMW heparin were used to term. The first 120 patients were treated with unfractionated heparin at 5,000 U every 24 hours, subcutaneously and the last 192 have been treated with Dalteparin at 5,000 U/day subcutaneously. The patients with MTHFR were also treated with folate at 5 mg/day + pyridoxine at 50 mg/day. All patients were carefully monitored with CBC and platelet counts, anti-Xa levels, frequent ultrasounds and physical exams. Only 2 of the thrombophilia patients suffered another miscarriage; all others had a normal term delivery. There were no pregnancy-related thromboses, no delivery complications and no episodes of post-partum thrombosis. The only bleeding consisted of 1-4 cm bruises at injection sites. No episodes of thrombocytopenia (HIT) were noted. In our experience, thrombophilia is a common cause of recurrent miscarriage and all patients with no anatomical, hormonal or chromosomal defect should be evaluated for thrombophilia or a bleeding disorder. The success rate of normal term delivery in these 312 patients was 94% using ASA + heparin or Dalteparin. In addition, side effects of therapy were minimal.


Acta Obstet Gynecol Scand. 2000 Aug;79(8):655-9.
Birth outcomes in pregnant women treated with low-molecular-weight heparin.

Sorensen HT, Johnson SP, Larsen H, Pederson L, Nielsen GL, Moller M

The Danish Epidemiology Science Center at the Department of Medicine V, Aarhus University Hospital.

BACKGROUND: Pregnancy and puerperium are associated with an increased risk of venous thromboembolism. Low-molecular-weight heparin is the anticoagulant of choice in pregnant women because, unlike warfarin, it does not cross the placenta. However, there are limited data on the risk of adverse birth outcomes following use of low-molecular-weight heparin in pregnancy. PATIENTS AND METHODS: We performed a population-based cohort study to examine the safety of low-molecular-weight heparin use in pregnancy using data from the Pharmacoepidemiological Prescription Database, The Danish Medical Birth Registry and the Regional Hospital Discharge Registry in North Jutland County, Denmark. The birth outcomes in a cohort of 66 pregnant women treated with low-molecular-weight heparin between 1991-98 were compared with the birth outcomes of 17,259 pregnant women who did not receive any prescriptive drugs during pregnancy. RESULTS: No increased risk of malformations, low birth weight or stillbirth was found. However, an increased risk of pre-term delivery was found (odds ratio: 2.11, 95%, confidence interval: 0.96-4.65), which could reflect inherited thrombophilia as an indication of low-molecular-weight heparin. CONCLUSION: We have provided additional evidence of the safety of low-molecular-weight heparin use in pregnancy.


Fertil Steril. 2005 Sep;84(3):770-3.
Effects of enoxaparin on late pregnancy complications and neonatal outcome in women with recurrent pregnancy loss and thrombophilia: results from the Live-Enox study.
Brenner B, Ellis M, Yarom I, Yohai D, Samueloff A, Live-Enox Investigators

Rambam Medical Center, Haifa, Israel.

Women with thrombophilia and a history of recurrent pregnancy loss have poor pregnancy outcomes. Prophylaxis with enoxaparin 40 mg/day or 80 mg/day resulted in favorable gestational and neonatal outcomes.

PMID: 16169422 [PubMed - in process]


  1. Here is some additional information about the "genetics" of this condition that was written by our Genetic Counselor and other genetic professionals: I hope it helps. Thanks, AccessDNA

  2. here i love to share a blog about women health
    pregnancy and tubal reversal

  3. I like what I read and im gone take it to my doctor because I had 3miscarraigesand 1stillbirth:(

    1. Your case is calling for proper treatment.
      You are a patient and your doctor should be familiar with the new advances in medicine.

  4. Yesterday, May 23,2013 I saw an Internal Medicine doctor in Calgary, Alberta, and she replied to my concerns about having multiple pregnancy losses and Factor II that no matter if I am on Lovenox or not my chances of miscarrying again are the same. And she also stated that Lovenox works solely on the veins not the arteries, and the arteries are what flow into the uterus, so when conception occurs and implanation takes place the Lovenox can not help the outcome and it is not possible for me to throw a clot into my uterus killing the fetus. This conversation took away all hope I had for my current pregnancy to progress. I walked out of this office with no hope and I thanked her for taking that away from me. However, this article has helped me feel better about my situation and its outcome.

    I had a miscarriage in 2013. We’d only been trying to get pregnant for a couple of months, and when I got that first positive pregnancy test, it felt a little bit like a whoops! Well, okay. One evening, I came home from a book reading and was bleeding. I quickly turned to all my pregnancy books, and to the internet, all of which told me that a little bleeding could be normal and fine, but the longer it went on, and the more pain I was in, what was happening became clear. The bleeding wasn’t stopping, and neither was the pain. Even though it was obvious enough what was going on, I refused to take any pain medication. Because you’re not supposed to take blood thinners when you’re pregnant. That was how I lost my first pregnancy. And in two others in the same year I had to look for solution, because our family Doctor could not help, he has given us a lot of prescription but non worked, I had to look for solution on line and saw the contact of Dr Steve I contacted him through the mail and made purchase for his product which is a permanent solution to Miscarriage. Now am having two kids and I promise to tell the whole world about him if he helps me out. You can contact him for solution on for a good solution to miscarriage.