Pregnant women with clotting disorders are often prescribed a challenging and cringe-inducing treatment — daily doses of a blood-thinner injected into the abdomen — in a bid to prevent a miscarriage or other complications. But a long-term clinical trial has found that the widely used therapy is ineffective in most cases and puts women through unnecessary pain.
Up to one in 10 pregnant women are at risk of developing blood clots in their veins, a condition known as thrombophilia. Over the last 15 years, many doctors have treated women with an anticoagulant drug called low molecular-weight heparin (LMWH), with the idea that it could prevent blood clots in the placenta that can cause such complications as miscarriage, pre-eclampsia and underweight infants.
Over the course of the pregnancy, a woman could end up poking herself with needles up to 400 times, leaving a patchwork of bruises across the belly.
Heparin injections not only cause bruising, but they can also result in minor bleeding episodes involving the nose, gums or vagina. The treatment is also expensive, running to about $4,000 in total, a cost not covered by most provincial insurance plans.
Clotting increases risk of complications
The idea of using heparin began after studies showed that women with thrombophilia have an increased risk of pregnancy complications, said Dr. Marc Rodger, a hematologist and senior scientist at the Ottawa Hospital Research Institute.
"What's happened over the 15 years is it's gone from an idea to some early preliminary evidence that suggested that it worked to prevent blood clots in the placenta and hence pregnancy complications," he said. "It became standard of care in many institutions across the world — even before there was good solid evidence that comes from doing randomized trials."
'I'm very glad that we can now spare these women all those unnecessary needles.' - Dr. Marc Rodger, Ottawa Hospital Research Institute
Twelve years ago, Rodger began an international trial that enrolled women with a clotting disorder to see whether daily heparin shots indeed helped prevent pregnancy complications compared to getting no treatment.
"And its turns out it doesn't," said Rodger, who admitted to being somewhat surprised at the findings.
The study, published online Thursday in the Lancet, enrolled 292 women with thrombophilia, who were being seen by doctors at 36 centres in Canada, the U.S., Europe and Australia. Half were randomized to self-inject heparin — one needle per day for the first 20 weeks, then two daily for the balance of their pregnancy — while the other half, the control group, got no blood-thinner treatment.
"About 17 per cent of participants in the control group had complications and an almost identical percentage had complications in the blood-thinner group," said Rodger, adding that more than 80 per cent of women in both groups did not experience a major pregnancy complication.
"There was no difference between those who got the needles and those that didn't get the needles in terms of percentages that got complications." he said.
Among women who did have a complication, they were roughly evenly matched in both the treatment and control groups: eight per cent miscarried; six per cent had low birth-weight babies; four per cent had pre-eclampsia, a serious high blood-pressure disorder; and about one per cent developed a major blood clot that was treated with a blood-thinner.
"While I wish we could have shown that LMWH prevents complications, we actually proved it doesn't help," said Rodger. "However, I'm very glad that we can now spare these women all those unnecessary needles."
'It can be disillusioning'
Ottawa lawyer Allison McIntosh, 34, pinned her hopes on the injections during her third pregnancy, which followed two miscarriages. For about 10 weeks, she gave herself daily heparin needles, only to find out the treatment had been ineffectual when she miscarried for the third time.
"It was difficult after realizing that the injections didn't work," McIntosh, who was unavailable for an interview, said in a statement. "I thought that I was doing something to make a difference by giving myself the injections. I kind of lost hope after that experience."
Now six months into her fourth pregnancy, having decided with her husband against the injections, McIntosh said she's not surprised to hear the treatment appears to have been disproven. "I feel sad for other people who are going through that process. It can be disillusioning for people if those injections are their only hope."
However, Rodger said there is one type of thrombophilia — called anti-phospholipid antibodies — for which blood thinners may be effective in preventing recurrent pregnancy loss, based on the findings of several clinical trials.
Angela Donatucci found out she carried the antibodies after two early miscarriages in the last two years, and she opted to go on the injections when she became pregnant a third time.
"I have a phobia of needles, so it was probably the last thing I was expecting to do," said Donatucci, 44, who's seven months' pregnant. "It's been OK because my husband's the one that administers them."
She started using a topical skin anesthetic that can relieve the ouch of the shots, but before discovering the existence of freezing, she admitted "it hurt."
"It's not pleasant. I wouldn't wish it on anybody to have to do this," Donatucci, whose abdomen is covered in bruises from her two daily injections, said Thursday from her Ottawa home. "I won't lie to you, there were times when I cried because I wished I were done with this."
But Donatucci believes the injections are working and have stopped her from having a third miscarriage.
"For me, knowing that I'm blessed and I'm hopefully going to make it to the end with a healthy baby, it's just a minor sacrifice."
Rodger conceded the study's main conclusion may result in pushback from some doctors.
"There are people who are completely bought in in my community of experts in thrombosis (blood clots) and pregnancy complications. So yeah, this will come as a shock to them, and they may try to poke holes in it. We think we've done a good job with the study, but there may be calls for further research in smaller subgroups (of patients)."
In an accompanying commentary in the journal, Drs. Paul Gibson and Kara Nerenberg write that physicians' altruistic intentions to treat women at high risk of devastating pregnancy complications might have inadvertently caused them at least some minor harm.
"The (study) investigators should be congratulated for completing this much-needed, rigorous trial, which ... clearly shows that low molecular-weight heparin is ineffective in preventing a wide range of clinically important adverse pregnancy outcomes in women with thrombophilia," they write.
"Hopefully, these results will finally tip clinicians away from using the drug in this setting and motivate researchers to pursue other potentially effective preventive interventions."