Prevalence of low-molecular-weight heparin prescription in pregnant women according to level of venous thromboembolic disease risk

By Dr. Liji Thomas, MDMay 2 2022Reviewed by Danielle Ellis, B.Sc.

The increased pregnancy rate at relatively advanced maternal age has led to higher rates of thromboembolic disease (TED), complicating pregnancy. A new paper discusses low-molecular-weight heparin (LMWH) in the prophylaxis and treatment of this condition.

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Introduction

Earlier research shows that the risk of TED in pregnancy and the postpartum period exceeds the baseline risk by 4-5 times in women. The risk is further heightened by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the agent causing the current pandemic of coronavirus disease 2019 (COVID-19). For this reason, more and more women are being prescribed LMWH during pregnancy in an attempt to forestall this complication.

The present study, published on the medRxiv* preprint server, was carried out to determine how often LMWH was prescribed in pregnancy, the risk classification of such women based on the ETV-OBS risk calculator, and how the risk varied with the occurrence of SARS-CoV-2 infection. The retrospective study included 113 women who delivered their babies in February 2022 at the Hospital Universitario Puerta de Hierro Majadahonda (HUPHM).

What did the study show?

The women included in the study were mostly younger than 35 years, with almost 32% being between 36 and 40 years, and 7% aged 41-45 years. About 45% were between 1 to 35 years old, and one in seven were aged 26 to 30.

Bodyweight measurements showed that over 60% were of normal weight, and over one in five were overweight. Only 7% were obese, however, while less than one in ten were underweight. Just over a tenth were smokers during pregnancy.

Almost 40% were delivering for the first time, comprising half of the 21-25 years age group but two-thirds of those aged 26-30 years. Between 31 and 35 years, 38% were primigravidas, but less than 30% between 36 and 40 years, vs. 43% of women aged 41-45 years.

None had a prior thromboembolic episode, while 2% had a family history of venous thromboembolism (VTE). A similar number had gone on a long trip, and again, the same proportion reported immobilization during the first trimester vs. none in the third trimester. However, 14% of third-trimester mothers had SARS-CoV-2 infection in the third trimester but less than 1% in the first.  

Sixteen women with risk factors for VTE in the first trimester, but 20 in the third, mostly because of more pregnancies with pre-eclampsia. While 97% of women were at low risk in the first trimester, this rose to 90% by the third trimester. A few patients were at intermediate risk in the first trimester and 10% by the third trimester, but no high-risk patients were found at any point.

A third of the patients had no low-risk factors in the first and an almost similar number in the third, compared to 44-45% who had one factor. Two factors were present in 17%, and 5-6% had three or more risk factors. Less than 1% had four risk factors in the first trimester, and none had five at this point. Conversely, no patient had four factors in the last trimester, but <1% had five during this period.

Two patients were put on heparin in the first trimester due to the risk of VTE as well as of previous abortions. Conversely, 11 women in the last trimester were on heparin, all because of SARS-CoV-2 infection, with one also having a history of abortion and risk factors for VTE.

ASA was prescribed for two first-trimester and six third-trimester patients. In either group, half of them were at risk for pre-eclampsia. In the first group, the others had a positive family history. In the other group, the rest were equally divided between a history of recurrent abortion and a family history of VTE.

Over half the women had natural deliveries, while over a fifth had Cesarean sections. Less than a tenth were preterm deliveries.

In the puerperium, about 90% were at low or intermediate risk of VTE. All high-risk patients were given heparin and ~70% of intermediate-risk patients. Of the low-risk patients, only one in five were on LMWH.

Overall, half of the women in the study were given LMWH, the majority being at intermediate risk and over one in seven at high risk of VTE.

What are the implications?

This is the first study in Spain that has followed the risk factors of 108 women throughout the pregnancy using the same criteria to analyze the prescription patterns of LMWH during this period. The results bear out earlier research based on the population at large.

While 40% of the women were primigravidas, the greatest increase in risk, by about 13 points, was due to COVID-19 caused by Omicron, which covered the same period as the third trimester of pregnancy of the women in this study. This is mirrored by the higher number of LMWH prescriptions this trimester, despite a lack of correlation with the baseline risk. This lack of correlation was mainly because SARS-CoV-2 was not included as a risk factor.

The reduction in the number of low-risk patients throughout pregnancy and the puerperium is due to the addition of patients who had a C-section to other at-risk patients. The relatively higher C-section rate is higher than the institutional average but is comparable to the national average.

Over half of pregnant women are prescribed heparin for at least 10-14 days at some point. In this study institution, Royal College guidelines were followed to prescribe this drug. Heparin is recommended when two or more risk factors are present in the puerperium. However, in this study, almost 81% of patients had one or more risk factors at this point.

The comparatively higher proportion of LMWH prescription may be attributed to the higher average age of the women in this study, the higher rate of C-section, a higher rate of SARS-CoV-2 infection, and in vitro fertilization (IVF). It should be noted that up to a third of maternal deaths are due to pulmonary thromboembolism, which ranks seventh as a cause of death at this time.

Despite the known association of pregnancy and COVID-19 with VTE, only half of these patients were put on LMWH, probably because criteria were used for the recommendation. While conservative physicians often chose not to administer LMWH, citing the lack of scientific evidence, others chose to empirically prescribe it to compensate for the increased risk of VTE due to COVID-19.

The researchers comment, “An assessment of thrombotic risk factors should be made in all pregnant women at the beginning of pregnancy, and should be repeated if any change in the variables is produced, as well as at the time of delivery and postpartum. All this requires that patients receive information, training and that they are discharged with the prescribed drug for self-administration.”

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.