But LMWH prophylaxis associated with an increased risk of late obstetrical complications

Women with type 1 antithrombin deficiency had not only a high risk of developing a venous thromboembolism (VTE) during pregnancy and in the initial 6 weeks following delivery but also a high risk of developing late, placenta-mediated obstetrical complications as well, a retrospective, single-center analysis has indicated.

In 80 woman evaluated for VTE risk during pregnancy, 7.0% (95% CI, 1.8-17.8%) of women treated with prophylactic low molecular weight heparin (LMWH) developed VTE compared with 11.6% (95% CI, 7.2-17.6%) of those who did not receive LMWH, Maria Abbattista, MD, Ospedale Maggiore Policlinico, Milan, Italy, and colleagues reported in the Lancet Haematology.

“In women with a positive family history of venous thromboembolism, no events of venous thromboembolism were observed in 16 pregnancies with LMWH, and 11 events (eight deep vein thrombosis, one cerebral vein, and two superficial vein thrombosis) in 93 pregnancies without LMWH (12%),” the study authors wrote. “In women with a negative family history, no events of venous thromboembolism were observed in 11 pregnancies with LMWH and two events of deep vein thrombosis in 37 pregnancies without LMWH (5%).”

However, prophylactic LMWH is not a panacea against VTE risk, as late obstetrical complications occurred in 24% of women treated with LMWH compared with 6% of those who were not, at a relative risk (RR) of 4.4 (95% CI, 1.9-9.9; P=0.0006), researchers also reported.

“To our knowledge, this is the largest cohort of pregnant women with antithrombin deficiency that has been reported to date,” Abbattista and colleagues observed.

“If the increased risk of late obstetrical complications in women receiving LMWH is confirmed, it should be taken into account when prescribing antithrombotic prophylaxis in women with an antithrombin deficiency,” they cautioned.

Asymptomatic women without a history of VTE as well as symptomatic women with a history of VTE received intermediate prophylactic doses of LMWH, 40 mg, once a day or 60 mg if their body weight was in excess of 60 kg.

As the authors pointed out, LMWH is the anticoagulant of choice for the prevention and treatment of VTE in pregnancy.

LMWH was initiated at the same time when women underwent their first obstetric ultrasound at 7 to 10 gestational weeks.

Women who were taking an oral anticoagulant already or those who were asymptomatic but considered to be at high risk for a thrombotic event received therapeutic doses of LMWH.

“All women had the prescription so that they could continue LMWH prophylaxis during the puerperium [period 6 weeks after delivery],” the authors noted.

If a woman had been on anticoagulant therapy before becoming pregnant, they could resume treatment soon after delivery at their physician’s discretion.

A VTE event could include proximal deep vein thrombosis (DVT) or pulmonary embolism (PE).

Considering DVT only, 2.3% (95% CI, 0.4-12.1) of women who were treated with LMWH during pregnancy had a DVT compared with 4.1% (95% CI, 0.9-8.7%) of women who did not receive LMWH during pregnancy, as the authors reported.

In the 6 weeks following delivery, 3.1% (95% CI, 0.6-15.7%) of women who continued to receive LMWH developed a DVT compared with 4.3% (95% CI, 1.8-8.7%) of women who did not.

“Overall, the incidence of pregnancy-related venous thromboembolism was higher in symptomatic…than in asymptomatic pregnancies,” at 22% versus 8%, investigators pointed out.

The risk of VTE in women who were not treated with LMWH was also higher in women with a positive family history of VTE at 11.8% (95% CI, 6.4-19.6%) compared to those with a negative family history at 5.4% (95% CI, 0.9-16.7%), they added

Pregnancy Outcomes

“Pregnancy outcome was evaluated in 87 women,” the authors continued.

The use of prophylactic LMWH slightly decreased the risk of miscarriage, which occurred in 13% of women treated with LMWH compared with 20% of those who were not.

However, the risk of late placenta-mediated obstetrical complications was significantly higher among women who were treated with LMWH compared to those who were not even though this was true only for asymptomatic women, the effect from LMWH prophylaxis disappearing in symptomatic patients, as researchers observed.

Limitations of the study include the absence of a control group of patients without thrombophilia which didn’t allow researchers to calculate the absolute risk difference of VTE and obstetrical complications between the 2 groups.

In addition, the VTE events that were observed in pregnancies where women were treated with prophylactic LMWH were all recurrences.

“The poor preventative efficacy of LMWH might [therefore] be attributable to the therapeutic dose,” the authors suggested, adding, nevertheless, that “our results support routine LMWH prophylaxis for prevention of venous thromboembolism in pregnant women with antithrombin deficiency, even in those with a negative family history of venous thromboembolism, which differs from other recommendations,” they concluded.

New Information

Commenting on the findings, Mirjana Kovac, MD, University of Belgrade, Belgrade, Serbia, felt that the study provides some important new information.

Firstly, the authors demonstrated that women with type 1 antithrombin deficiency are at high risk for obstetrical complications when treated with prophylactic LMWH compared to those who are not.

“This finding is surprising and deserves further research,” Kovac suggested.

Moreover, “full therapeutic doses used in women with recurrent venous thromboembolism were not sufficient to prevent new events in this population,” as she also underscored.

On the other hand, none of the pregnant women in the study received any antithrombin substitution, which in her own experience at least with type II antithrombin deficiency, substitution of antithrombin concentrate along with LMWH is recommended. (Women with type II antithrombin deficiency were excluded from the Italian study).

Given that the use of LMWH without antithrombotic concentrate did not appear to be beneficial for women with recurrent VTE, “for type 1 antithrombin deficiency, the use of antithrombin concentrate should be considered in women who have had a previous thrombosis, or in the treatment of acute pregnancy-related venous thromboembolism,” Kovac recommended.

For both symptomatic and asymptomatic women with antithrombin deficiency, Kovac also recommended that additional risk factors including age, the presence of comorbidities, obesity and varicosities should be evaluated as well in order to decide on the optimal prophylactic anticoagulant dose and whether these is a need for antithrombin substitution and laboratory monitoring.

  1. This study suggests that women with type 1 antithrombin deficiency were at high risk of developing VTE during pregnancy and the initial 6 weeks following delivery.

  2. Be aware that high-risk women treated with prophylactic LMWH during pregnancy had a much higher risk of late, placenta-mediated obstetrical complications compared with those who were not treated with prophylactic LMWH.

Pam Harrison, Contributing Writer, BreakingMED™

Abbisttista had no conflicts of interest to declare.

Kovac declared no competing interests.

Cat ID: 41

Topic ID: 83,41,730,41,192,925