Anticoagulation treatment in pregnancy

In a normal pregnancy various changes may occur in the circulatory system of the woman. These changes result to venous stasis that affects the haemostatic mechanism causing “hypercoagulation”.

Author
Efimia P. Vrakidou
Hematologist, HYGEIA Diagnostic & Therapeutic Center of Athens

Hypercoagulation can be the result of reduced capillary blood flow. It can also be attributed to the reduction of the natural coagulation inhibitors such as protein C and, finally, to educed fibrinolysis.

Venous stasis is favoured by various factors during pregnancy, i.e. high levels of estrogens and the pressure imposed to the abdomen vessels by the enlarged uterus.

As a result, the risk for a woman to have venous thrombosis or pulmonary embolism during pregnancy is about 6 times higher than that of a woman that is not pregnant. Pulmonary embolism is the leading cause of death in pregnancy.

Risk factors for venous thromboembolism in pregnancy

The main factors that increase the risk for venous thromboembolism in pregnancy are the following:

Age of the mother over 35 years (the risk is double).
Obesity (body weight over 80kg).
C-section and particularly emergency cesarean.
History of venous thrombosis or pulmonary embolism (relapse rate of 5 to 15%).
Number of pregnancies higher than 4.
Immobility, varicose legs.
Preeclampsia.
Congenital or acquired thrombophilia (Antiphospholipid Syndrome).
Puerperium.

Recurrent miscarriages and other obstetric complications

Recurrent miscarriages (over 2 or over 3 depending on the literature source) are a common problem for about 1 to 2% of women in reproductive age. The causes are various. Some indicatively causes are as follows:

Abnormalities in the uterus (5%).
Chromosomal abnormalities (5%).
Infections (5%).
Various hormonal factors (5%).
Antiphospho-Lipid antibodies (35%).
Other antibodies (5%).
Mutation of factor V (Leiden factor).
Other haemostasis abnormalities (10%).
Without a clear cause (20%).

Antiphospholipid antibodies are usually associated with miscarriages in the first trimester of pregnancy. Congenital thrombophilia has been associated with miscarriages in the second trimester. In about 49% of women with recurrent miscarriages, some form of thrombophilia mainly associated with factor V (Leiden) is present. In the later years, it is concluded that the mutation of both factor V (Leiden) and prothrombin, triple the risk for miscarriage. Disorders of the homocysteine gene are associated to miscarriages early in pregnancy. The deficiency of factor XII (Hageman) is associated with recurrent miscarriages in about 2.9% of women. Various complications such as preeclampsia, abruptio placentae, fetal growth inhibition and fetal death have been attributed to thrombosis of the capillaries of the placenta and were associated with thrombophilia.

Classification of women according to the risk for venous thromboembolism

Low-risk patients
Family history of thromboembolism.
Patients with Protein C or protein S deficiency and patients with heterozygous Leiden factor that have or have no family history of venous thromboembolism.

Middle-risk patients
Patients with homozygous Leiden factor without a preceding incident of thrombosis or embolism that do not have a family history.
Patients with heterozygous Leiden factor without a preceding incident of thrombosis or embolism that do not have a family history.
Patients that have undergone an incident of thrombophilia, thrombosis or embolism.
Patients with a family history of recurrent miscarriages or serious preeclampsia and/or thrombophilia.

High-risk patients
Patients with acute thromboembolic stroke during this pregnancy.
Patients with prosthetic heart valves.
Patients with antithrombin ΙΙΙ deficiency.
Patients with a history of recurrent thromboembolic complications.
Patients with various thrombophilic factors with or without an incident of venous thromboembolism.

Therapeutic treatment for venous thromboembolism in pregnancy

In order to conclude on the anticoagulation scheme that should be followed to treat or prevent venous thromboembolism in pregnancy a series of factors should be taken into account. These factors are mainly the safety of anti-coagulant administration for the mother and the fetus, effectiveness of the anti-coagulant, dosage scheme for the treatment of the acute thromboembolic stroke or for the protection of high-risk women during pregnancy, labor and lactation. More specifically:

(a) Safety of the anti-coagulant administration for the mother and the fetus

Standard heparin and the low molecular weight heparins do not cross the placenta and, therefore, are considered to be safe for the fetus. On the contrary, coumarins do cross the placenta and might cause embryonic abnormalities and bleeding. The potential complications for the mother by the use of anti-coagulants include bleeding, osteoporosis, thrombocytopenia (when heparin is administered) and skin necrosis (when coumarins are administered).

(b) Effectiveness of the anti-coagulants in pregnancy

Heparin and the low-molecular-weight heparins (LMWH) are thought to be effective for the treatment of and prevention against thromboembolic strokes in pregnancy with some reservations for the case of women with prosthetic heart valves. LMWH exhibit a more favorable profile compared to standard heparin and their use does not require a regular hematological monitoring.

Anti-coagulation treatment during labor

Heparin and LMWH treatment should be discontinued 24 hours before scheduled induction of labor or cesarean delivery. Occasionally, in very high risk patients, treatment should be discontinued 4 to 6 hours before labor. In the case of spontaneous labor, special medication is administered to avoid serious bleeding. It should be noted that epidural anesthesia is not recommended. Heparin and LMWH treatment can be continued 12 hours after delivery. All anti-coagulation schemes are safe for nursing mothers.

Anti-coagulation treatment in women in high risk for miscarriage or complications and in women with antiphospholipid antigens

Women with recurrent miscarriages (over 3) should be tested for antiphospholipid antibodies. These women should be checked for congenital thrombophilia in the case that the miscarriages include one or more miscarriages during the 2nd trimester of pregnancy. Moreover, women with a history of severe or recurrent preeclampsia, delayed fetal development, abruptio placentae or unexplained fetal death should be checked for congenital thrombophilia and antiphospholipid antibodies. Those women should receive low doses of aspirin (100mg) in combination with prophylactic doses of LMWH during pregnancy.
Women homozygous to homocysteine should take folic acid before conception or the earliest possible after the detection of the pregnancy.
Women with thrombophilic disorders and multiple miscarriages or fetal death during the 2nd or 3rd trimester of pregnancy or, finally, preeclampsia, intrauterine death or abruptio placentae, should be encouraged to take low doses of aspirin and also prophylactic doses of LMWH and anti-coagulation treatment during puerperium.
Women with antiphospholipid antibodies and a history of venous thrombosis should take anti-coagulation therapy due to increased risk for relapse. These women should receive therapeutic doses in pregnancy and long term therapy during puerperium.
Women with antiphospholipid antibodies without a history of venous thrombosis or miscarriage should considered as high-risk patients for thrombosis and potentially for miscarriage. It is recommended that these women receive prophylactic doses of heparin or low dose aspirin.

It should be noted that all the above mentioned problems can be effectively treated in pregnant women or women that miscarried and are currently trying to get pregnant again. Treatment heavily relies on the causes of the problems. Every woman has the right to be a mother.