Use of heparin to prevent gestational loss

Thrombophilia is directly related to gestational failure. Dr. Fariñas, an expert in Hematology, talks about the use of heparin in patients with numerous miscarriages, over 35 years of age and thrombophilia.

Why does the gynecologist refer women with fertility problems to the hematologist?

To perform a thrombophilia study. Thrombophilia is the predisposition to venous thrombosis. Pregnancy is a procoagulant situation and in vascular complications of pregnancy it is even more intensified. Thrombophilia would increase it even more. Studies have mainly studied genetic venous thrombophilia, mainly Factor V Leiden mutation and prothrombin gene mutation. In 2005 a meta-analysis of case controls found a relationship between different thrombophilias and different types of gestational losses. Since then there has been controversy. In 2014 an important study objected that women who have had at least 3 miscarriages, if they also have Factor V Leiden mutation or prothrombin gene mutation have a higher risk of having a fetal loss of more than 10 weeks. On the other hand, anticardiolipin antibodies are seen in 15% of women who have had repeat miscarriages.

What is the use of heparin to prevent gestational failure?

Heparin could improve this procoagulant situation but not only from week 10 or 12 when the uteroplacental circulation is established but from the beginning of pregnancy, from the moment of implantation where hemostasis is fundamental. Besides, heparin has multiple effects to favor implantation and to favor trophoblast development and trophoblastic invasion. Is heparin proven to be useful in preventing repeat miscarriages? No, it has not been demonstrated in women who do not have thrombophilia. The reason is that the randomized trials have not had a sufficient number of patients, it has not been possible to study chromosomal alterations and in many of them it has not been possible to apply heparin from the beginning of pregnancy. At the present time, it is not clear that heparin will benefit a 35-year-old woman with two miscarriages, but in women over 35 years of age with at least two miscarriages there is insufficient evidence. In women with thrombophilia, randomized trials have been inconclusive because heparin has been applied from 10 weeks of gestation. However, very important observational studies with many patients do find heparin useful when heparin is applied from the beginning of pregnancy.

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Is thrombophilia related to implantation failures?

In 2006, Kubland found a relationship between implantation failure and thrombophilia. Subsequently there has been much controversy. Meta-analyses of case-control found with Factor V Leiden and with anticardiolipin antibodies, so that many authors suggest that thrombophilia studies should be performed in women who have had at least 3 implantation failures. Regarding the usefulness of heparin, randomized trials have found that in women with at least 3 implantation failures the pregnancy outcome at term is 78% higher than if heparin is not used, but the number of participants is small. In important but not randomized trials, benefit is found for heparin, but the number of participants is small and therefore it is suggested that urgent randomized studies be carried out. But randomized trials for women with repeated miscarriages have taken 10 or 12 years, so we wonder if a 37-year-old woman who has not had children, who has had 3 implantation failures, can wait for these randomized trials or can she use heparin at a prophylactic dose that can reduce the risk of thrombosis and perhaps help her achieve pregnancy.