Thrombophilia and thrombosis risk in pregnancy: everything you NEED to know

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Catherine Le Nevez
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During pregnancy, blood tends to clot more - a necessary measure to reduce the possibility of bleeding during childbirth. The downside, however, is that this trend can increase slightly the risk of thrombus forming (clots). Above all, this risk becomes even more significant if other factors, hereditary or acquired, are present that lead to a thrombophilic predisposition.



Let's see what exactly is meant by thrombophilia, what risks it entails, how to discover it and how to intervene, with the advice of the gynecologist Valentina and the hematologist Ida Martinelli.



In this article

  • what is thrombophilia
  • depends on what
  • what does it entail
  • the risks to the pregnant woman
  • screening exams
  • therapies
  • complications during pregnancy
  • drugs
  • how to reduce the risk of thrombosis

Thrombophilia and thrombosis, what are we talking about?

"Literally, the word thrombophilia means friend of the thrombus, that is, of the clot" explains the hematologist Ida Martinelli of the Hemophilia and Thrombosis Center of the Polyclinic of our city. "In other words, it is the predisposition to undergo thrombosis, therefore the formation of clots in the arteries or veins, due to an excessive tendency of the blood to clot ".



Thrombophilia is a condition that increases the risk of blood clots, which, if they do not dissolve or are not treated quickly, can put a woman's health at serious risk.

What does thrombophilia depend on?

During pregnancy, blood tends to clot more. "It is a physiological condition, which arises from the beginning, worsening in the last trimester and in the first weeks after childbirth: a strategy to prevent women from bleeding to death during childbirth," Martinelli points out.



This condition may slightly increase the risk of some thrombotic events, but the problem occurs in particular if other risk factors are present, such as: 

  1. Hereditary abnormalities of blood clotting

"Hereditary thrombophilias, ie with a genetic basis, are due to mutations in coagulation factors" explains the gynecologist Valentina, expert in high-risk pregnancies and consultant of the Ciaolapo Onlus association for the protection of pregnancy and perinatal health.

"Among the most frequent forms are those due to mutations in the factor V of Leiden and in factor II. Mutations in antithrombin, protein S and protein C are rarer mutations of the MTHFR gene, are to be considered thrombophilic only if present in duplicate, ie derived from both the mother and the father, and only if associated with an actual increase in the blood levels of a substance called homocysteine ​​".

Mutations in factor V, factor II and the MTHFR gene

Factor V Leiden mutation

Those with the factor V Leiden mutation have a mutation in their genetic makeup that predisposes the blood to a more marked tendency to clot.

In the case of the factor V mutation they exist two possible genetic assets: that omozigote, rarer, in which the risk profile for thrombosis increases 50 to 100 times, because the patient has both copies of the gene mutated. Shape heterozygous, on the other hand, it is the most widespread and leads to a more nuanced risk of thrombosis (5-10 times), because the patient receives the mutated copy of the gene from only one of their parents.

 

Factor II mutation

The presence of the G20220A mutation, called factor II, is associated with high levels of prothrombin in the blood which can lead to abnormal clot formation and therefore to a greater risk of deep vein thrombosis and venous thromboembolism. In particular, heterozygous subjects for this mutation have a 3 times higher risk of developing venous thrombosis than non-mutated subjects.

 

MTHFR mutation

The MTHFR mutation is a genetic defect which causes the reduction or loss of activity of an enzyme, methylene-tetrahydrofolate reductase. The consequence is an increase in homocysteine ​​values ​​in the blood and a reduction in plasma levels of folic acid. The MTHFR mutation is considered a risk factor for the development of thrombosis, miscarriages and neural tube defects.

Overall, hereditary thrombophilias are present in about 15% of the Western population and are responsible for over 50% of venous thrombosis pregnant.

  1. Acquired abnormalities of blood clotting

"Among the acquired forms, however, we reorder the antiphospholipid antibody syndrome, an autoimmune disease that can increase the chances of having complications during pregnancy".

Finally, other aspects may also increase the risk of thrombotic events pregnant. For example age (the further you go, the more the risk increases), obesity, especially if associated with excessive weight gain in the nine months, cigarette smoking, excessive sedentary lifestyle.

Read also: Mom at 40, here's what you need to know

What does thrombophilia involve?

The tendency to excessive blood clotting can lead to the formation of thrombi, i.e. clots, with different consequences depending on the blood vessel affected. "We have to distinguish the artery, which carry oxygenated blood from the heart to peripheral organs, and the vene, which do the opposite, bringing oxygen-poor blood from the periphery to the heart, which sends it to the lungs where it is oxygenated again "explains Martinelli.

Le arterial thrombosis they give consequences such as stroke or heart attack. However, pregnant women have no different risk than the general population for this type of thrombosis. What happens, however, is that for them it increases the risk of a little thrombosis of the veins.

Venous thrombosis

"Venous thrombosis they typically affect the legs, and usually only one of the two "says Martinelli." The main symptoms are swelling of the leg, a sense of tension, pain. "If these signs occur, it is better to notify the doctor immediately, especially because, in a small percentage of cases, thrombosis in the legs can give a serious, potentially fatal complication, which is thepulmonary embolism.

"Unfortunately, the symptoms of embolism are initially subtle: difficulty breathing, some general fatigue" explains the hematologist. In any case, while it is good to keep this risk in mind, it is also fair to remember that we are talking about rare situations: "Every year, about 10.000-5 cases of thrombosis occur in every 10 pregnant women, and of these only a few lead to pulmonary embolism."

In addition, there are risks associated with the possibility of placental thrombosis during pregnancy.

Placental thrombosis

The placenta, as we all know, is the organ through which the mother nourishes and oxygenates the fetus. If clots form at the placental level, the blood cannot circulate well and this can have consequences both for the fetus, which is no longer growing optimally, and for the mother herself since placental abnormalities are linked, for example, to risk. of preeclampsia.

Possible symptoms of placental thrombosis are therefore preeclampsia (manifested by increased maternal pressure and increased protein in the urine) and fetal growth retardation.

Pelvic thrombosis

Blood clots may also affect the groin area, and particularly the veins in the pelvis (iliac vein thrombosis). In this case we are talking about pelvic thrombosis, the symptoms of which are not always evident. Pelvic thrombosis could manifest itself with:

  • groin pain;
  • swelling of the leg;
  • abdominal or back pain.
Read also: Pregnancy, SOS swollen legs and feet

What are the risks of a pregnant woman who also has hereditary or acquired thrombophilias?

According to the conclusions of a review of the scientific literature on the subject, published by a group of gynecologists at the University of Manchester, women with hereditary or acquired thrombophilia appear to be at a higher risk of experiencing early or late pregnancy complications. In particular:

  • recurrent miscarriages; 
  • preeclampsia;
  • premature birth; 
  • placental abruption; 
  • fetal growth retardation;
  • stillbirth of the child.

The problem is that we do not yet know exactly how to quantify this risk: Different studies have yielded different results, some emphasizing and others limiting or even excluding the possibility of an association between thrombophilia and risks in pregnancy. "Overall, we can say that the association exists, but it is weak"says Martinelli." After all, we must think that obstetric complications are often multifactorial, that is, dependent on a combination of factors and not only on thrombophilic risk ".

Is there a test to see if you are at risk for thrombophilia? Who should perform it?


Yes, there is a battery of tests to assess whether the clotting factors are "in order" or if something is wrong. This is the so-called screening trombofilico, performed through a simple blood test.

According to the Guidelines of the Del Paesena Society for the study of hemostasis and thrombosis (Siset), this test should include the analysis of the following factors: antithrombin, protein C, protein S, resistance to activated protein C and / or factor V Leiden, G20220A mutation, prothrombin, homocysteine, antiphospholipid antibodies.

Screening should be done when planning a pregnancy, and not when this has already begun, precisely because the changes in coagulation associated with this state tend to distort the results. In any case, according to the Guidelines, this screening is not indicated for all pregnant women, but only for some categories:

  • women who have already had venous thrombosis, or with close relatives who have suffered from it (family history);
  • women who have a family history for hereditary thrombophilia;
  • women with recurrent miscarriages (the search for antiphospholipid antibodies is highly recommended) or those who have had one fetal death in utero in a previous pregnancy, as also indicated by a recent review of the scientific literature;
  • women who, in a previous pregnancy, have had episodes of preeclampsia or HELLP syndrome (a particular form of preeclampsia), fetal growth retardation o placental abruption.
Read also: Hellp syndrome in pregnancy: what it is, how it manifests itself, how to intervene

THE COMMENT: BECAUSE SCREENING IS NOT SUITABLE FOR EVERYONE


Following the cases of maternal and fetal death that occurred in our country in the last week of 2022, there are those who have proposed the extension of thrombophilic screening to all women planning a pregnancy, but the idea was negatively received by the bulk of the scientific community.

"This is for various reasons that do not simply have to do with the cost of the test, as has been hypothesized" explains gynecologist Valentina. "First, because they are exams that can give many false positives. This would lead to offering therapies to women who do not need them. Second, why however, they do not exhaust all the possible causes of thrombophilia, many of which are not yet known. ”It means that you may find yourself with a test that says everything is fine, and then have problems instead.

"Third, because even in the presence of a test that indicates something wrong, it is not always clear how to proceed: in some cases the use of preventive anticoagulant therapies is controversial ".

In the presence of a thrombophilic risk, are there any therapies that can prevent any complications of pregnancy?


Therapy to reduce thrombophilic risk is based on anticoagulants, in particular low-dose aspirin and low molecular weight heparin, which can be administered individually or together. Aspirin is taken by mouth, while heparin is injected under the skin, usually in the abdomen.


The Siset guidelines indicate exactly in which cases to administer the therapy, which - when indicated - should be started as soon as possible:

  • women who have had events of venous thrombosis;
  • women who have details alterations in thrombophilic screening, even more so if associated with complications during previous pregnancies, or with a family history of thrombosis or obstetric complications.

In the case of women with a family history of thrombosis or obstetric complications, but without alterations in thrombophilic screening, the guidelines suggest a more careful monitoring of pregnancy, without particular preventive therapies.

What should be done if there have been complications in previous pregnancies but thrombophilic screening is okay?

It may happen that complications such as growth retardation, placental abruption, preeclampsia or stillbirth have occurred in previous pregnancies, but screening for thrombophilia is in place. This is currently the most controversial situation and is not covered by the Guidelines. Some doctors and some centers believe it is useful to administer preventive therapies even in these cases, even in the preconception phase, despite the absence of scientific studies that definitively confirm their usefulness.


"The point is that the studies we have available do not yet tell us enough, and therefore the doctor must make decisions even outside of what is officially recommended" he comments. "Which obviously does not mean administering drugs at random, but on the basis of an accurate analysis of the personal and family history of your patient, of her lifestyle, or the indications of any other analyzes".

Other doctors and other centers have a more conservative position, and try to avoid or limit as much as possible the administration of anticoagulants outside the indications. "Don't forget that however we are talking about drugs"remembers Martinelli." Safe drugs, of course, but which by definition are not entirely free of side effects, and which can also pass the placenta and reach the embryo. For example, it happens with aspirin, and we have no studies that tell us whether something particular happens to people who have been exposed to aspirin in utero prematurely after many years or not ".

In case of serious complications in pregnancy, a thorough histological examination of the placenta it can help, even more than thrombophilic screening, in deciding what to do in subsequent pregnancies. "An examination of this type clearly highlights if there have been thrombotic events of the placenta. If so, it may certainly be worthwhile to carry out a preventive anticoagulation therapy in subsequent pregnancies "he declares." Not all centers, however, perform this examination in a sufficiently accurate and thorough way ".

Medicines can help, but they don't solve everything


We must not forget that, although potentially useful, the anticoagulants are not the panacea for all ills. "Those who deal with high-risk pregnancies experience first-hand that prevention with anticoagulants improves the outcome of pregnancies, but it must be said that this is not always the case. There are cases in which even these drugs are of little use" emphasizes Valentina.

"What's really important in these situations is that women are not left alone. It still happens today that, faced with a stillbirth, a woman is told that she was unlucky. Here, this must not happen: cases like this deserve all the attention and insights possible, beyond the therapeutic choices that are then made ".

In general, what can women do to reduce their thrombophilic risk in pregnancy?


"The first tip is to start think about it even before pregnancy begins"He suggests. Beyond particular predispositions, genetic or acquired, some situations that increase the risk can be modified. This is the case of smoking, excessive sedentary lifestyle, overweight or obesity.

In the absence of risk factors such as hereditary or acquired abnormalities, for prevent thrombosis in pregnancy you need to know the other risk factors and avoid them. Some precautions can be:

  • stop smoking;
  • eat in a balanced and healthy way, avoiding putting on too much weight;
  • exercise;
  • drink a lot of water;
  • avoid crossing your legs so as not to obstruct blood flow.

"The second piece of advice - he continues - is that of immediately schedule a visit with the gynecologist and first trimester exams, making sure that the first visit is carried out carefully and accurately ". Thoroughly evaluate the woman's personal and family history can give very useful information for the management of your pregnancy: it is right that women demand this attention.

Covid vaccination and thrombophilic risk, the recommendations of scientific societies

According to the new recommendations of the Del Paesena Society for the Study of Hemostasis and Thrombosis (SISET), the benefits of anti-Covid vaccination clearly outweigh the potential risks, which is why vaccination is recommended. also to patients with a previous history of thrombotic complications and to subjects with thrombophilic coagulation abnormalities. 

 

The Del Paesena Society of Human Genetics (SIGU), which has signed the recommendations of the SISET, is also of the same opinion. According to the two scientific societies, therefore, the presence of thrombophilic defects should not be considered as conditions that contraindicate vaccination.

 

 

Other sources used: information material from the Federation of Centers for the Diagnosis of Thrombosis and the Surveillance of Antithrombotic Therapies (FCSA); recommendations from the British Health System; guidelines SIGO, AOGOI, AGUI.

TAG:
  • thrombophilia
  • thrombosis
  • thrombotic risk
  • thrombosis in pregnancy
  • preeclampsia
  • termination of pregnancy
  • stillbirth
  • growth retardation
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