Utility of heparin in recurrent miscarriages

The role of low molecular weight heparin in women with repeated miscarriages originated in the 1990s, when several English researchers began to use it in conjunction with salicylic acid in patients who had suffered repeated miscarriages and in whom antiphospholipid antibodies were detected.

As good initial results were achieved in seven out of ten pregnancies, its use was subsequently extended to cases of congenital thrombophilia, i.e. women with low quantities of coagulation regulators, in whom spontaneous thrombosis easily arises, and even, with little justification, in other cases in which repeated miscarriages could not be related to demonstrable circumstances.

The scientific literature referring to these facts is full of contradictions, and there are many articles that advise against its use as well as those that do, although it should be mentioned that the most widespread doctrine is that of NO, except in cases of pregnancies with antiphospholipid antibodies.

Although I stopped being interested in this subject because of the amount of confusing literature, due to the request of some Gynecologists and patients to receive heparin, about three years ago I began to control the administration of heparin, although measuring the levels of heparin in the blood and adjusting the dose to stabilize the figures of antiXa factor in the blood around 0.3 Ul/Ml, and never less than 0.2 IU/Ml during the entire pregnancy.

Despite initial objections, I soon decided that it would be better to have the treatment monitored by a Hematologist with experience in the field of anticoagulants.

Heparin in repeat miscarriages: encouraging results

The first result in a patient with a history of three previous miscarriages resulted in an uneventful pregnancy and a healthy child. Since then, I have monitored the administration of heparin in controlled doses in women close to 40 years of age who had repeated miscarriages, and the results have been a pregnancy without miscarriage.

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Regardless of the existence of any biological circumstance related to thrombotic processes, the results have always been positive. The most important finding was the need to vary the dose of heparin, increasing it normally throughout the pregnancy in nine of the eleven patients, in order to maintain the levels of anti-Xa factor above 0.2 Ui/Ml.

The physiological changes that occur in a pregnant woman could justify the irregular response of heparin, so that the administration of fixed doses would be insufficient in a large number of patients.

The fact that it works in women without antiphospholipid antibodies or other biological abnormalities normally associated with thrombophilia has led to the idea that the efficacy of the treatment may not be directly associated with the antithrombotic capacity of heparin, but with its biological properties.

In fact, in several studies, heparin has been shown to stimulate various cytokines that promote growth and proper vascular rearrangement, trophoblast structure and chorionic villi in various situations, such as preeclampsia.

Other anti-inflammatory properties may also play a role. For example, with the association with low-dose aspirin.

Conclusions

For all these reasons, it is possible that the guidelines that currently deny the benefits of heparin in pregnancy in women with a history of repeated miscarriages may not be well founded and may require revision.

In conclusion, and in our experience -limited but encouraging- the use of heparin should be done by adjusting the dose to achieve adequate anti-factor Xa activity. The use of low fixed doses may be useful only in low weight women.

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It remains a topic of extraordinary interest, but large trials of a different design than those so far conducted are needed to establish firm recommendations.