When to Start Anticoagulation Therapy for Recurrent Early Pregnancy Loss | Fruit of the Womb
Fruit of the Womb
Fruit of the Womb

When to Start Anticoagulation Therapy for Recurrent Early Pregnancy Loss

For many years now, we have placed women with recurrent early pregnancy loss on low-dose aspirin (81 mg) and heparin, or low molecular-weight heparin such as lovenox, to help them improve their prospects for pregnancy outcome. In some instances this regimen is used because an acquired (e.g., lupus anticoagulant; antiphospholipid antibodies) or genetic (e.g., Factor V Leiden; MTHFR polymorphism; protein C, protein S, and antithrombin III deficiencies; prothrombin G20210 mutations, etc.) ‘thrombophilia’ (tendency to form or maintain blood clots) has been identified. In other instances it is used simply as ‘empiric therapy’ because no particular reason has been identified and, quite frankly, we know that we do NOT have all the answers, because patients request that “anything be done that can be,” and because on the whole it is a fairly safe regimen, although it can be somewhat expensive.

Under these circumstances and, particularly, when used as ‘empiric therapy’, even when a successful pregnancy results, we cannot be entirely sure if our treatment was the deciding factor or it if was simply the result of chance. The original thinking was that somehow the anticoagulation properties of these agents prevented abnormal clotting of the placenta that was preventing the early pregnancy from developing normally. In recent years, we have discovered that other factors may be equally, if not more, important in early growth and development of the placenta as I allude to in my response to our reader’s questions below…

• At Sat Jan 19, 02:46:00 PM 2008, ONE OUT OF SIX said…

Dr. T - what are your thoughts on starting lovenox prior to implantation - either right before, or right after ovulation? And is your opinion the same in regard to a natural cycle as opposed to an ovulation induction cycle in which ovulation is then triggered with HCG? Also - does the patient already being on a daily baby aspirin have an impact one way or the other?

It has been suggested to me that being on both baby aspirin and lovenox (40mg/once a day) could actually inhibit implantation by causing a bleed at implantation site.

Others have said this is not the case at all - and in fact the opposite is true - healthier blood flow to uterus will assist with implantation (that may have been prevented in the past by diagnosed clotting disorders - homo MTHFR C677T and hetero Factor V.)

Last question - can you move to Pittsburgh, PA so I can become a patient? ;-)

Thanks for your insight.

• At Fri Jan 25, 10:53:00 AM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To One out of Six: Flattery will get you an answer EVERY TIME! Personally, I rarely will start lovenox or heparin before midway through the luteal phase after spontaneous ovulation or ovulation induction (about day 20-21) unless you have documented antiphospholipid syndrome or another condition that requires chronic anticoagulation. The reasons for that are it may increase bleeding from the ovarian ovulatory site (and, personally, I have taken two young women, who were not even on lovenox or aspirin, to the operating room in the past month with bellies full of blood from that very thing) and I sincerely doubt it does much good until the embryo has reached the uterine cavity and attachment has actually taken place. With all that said and done, on prophylactic doses of lovenox such as you are taking, it probably would not hurt or put you at much risk.

With regard to recurrent early pregnancy loss, however, the anticoagulation properties of lovenox and aspirin may be LESS important than their roles in improving trophoblast invasion and migration! This may be especially true under those circumstances in which 'thrombophilic antibodies' such as lupus anticoagulants, antiphospholipid antibodies, and anti-?2-glycoprotein-1 antibodies are present. These antibodies can bind to the trophoblasts in association with ?2-glycoprotein-1 and impair both trophoblast invasion and migration that are necessary for early pregnancy success. Interestingly, heparin and lovenox can reverse the effects of these antibodies by blocking their binding to ?2-glycoprotein-1. Anyway, I will put your question and my answer into a brief post on this subject soon (and perhaps a larger series later on) so, thanks for reading, for the excellent questions, and best of luck!

Dr T
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