thrombophilia

Heparin Fails to Stop Miscarriages in Women With Inherited Thrombophilia

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No difference in live birth rates with or without blood thinner

Daily injections of low-molecular-weight heparin (LMWH) failed to improve live birth rates for women with a history of recurrent miscarriages and inherited forms of thrombophilia, a randomized trial found.

In the 326-patient study, live birth rates were a similar 71.6% in women who received LMWH versus 70.9% with standard pregnancy care alone (adjusted OR 1.08, 95% CI 0.65-1.78, P=0.77), reported Saskia Middeldorp, MD, PhD, of the University of Amsterdam.

“The conclusions and take-home messages are pretty clear and … end a debate of decades,” Middeldorp said during a press briefing at the American Society of Hematologyopens in a new tab or window annual meeting.

But “we should not say this a negative study,” she added. “What we can do in our offices, in our practices, is reassure women with a history of recurrent pregnancy loss that they have a 70% chance of having a healthy baby.”

Side effects, while mostly minor, were significantly more frequent in the LMWH arm, with 43.9% experiencing one or more adverse events versus 26.5% in the control arm (OR 2.17, 95% CI 1.32-3.55). Common side effects included easy bruising, skin reactions at the injection site, and minor bleeding.

Middeldorp said the findings suggest that women with recurrent miscarriages should no longer be tested for inherited thrombophilia, pointing out that elimination of this testing could save an estimated $4,000, along with the additional $3,500 in savings for LMWH injections over the duration of a pregnancy.

In the U.S., “many women do get thrombophilia testing when they’ve had recurrent miscarriages, and there can be a lot of pressure of doing something versus doing nothing,” said press briefing moderator Cynthia Dunbar, MD, of the National Heart, Lung, and Blood Institute at the NIH.

“I had recurrent miscarriages myself and at the time read the literature and decided I wasn’t going to push for that and it didn’t make sense, but it was a hard decision,” she told MedPage Today. “Luckily, I also had two successful pregnancies after three miscarriages — so I have some personal experience with this.”

Dunbar said she hoped the findings would “settle the issue,” and that patients will stop getting very expensive panels that then label them as having a disease even if they have never had a clot.

“It’s not necessarily information that is helpful in any way, expect making you very anxious,” she said. “I was very happy about this trial — not happy about the results, I guess, but happy that at least it’s clear and it was a very well-performed trial.”

Past studies have shown an association between recurrent miscarriages and inherited thrombophilia, while other research has suggested that clots in the developing placenta could be a causal factor in miscarriages.

In a prior trialopens in a new tab or window from Middeldorp and colleagues in which anti-thrombotic therapy failed to increase live birth rates for women with unexplained recurrent miscarriages, there was a hint of potential benefit for the very small subgroup of women with inherited thrombophilia, leading to the current trial.

“For inherited thrombophilia, the curtains are closing in terms of aspirin and anticoagulants,” said Middeldorp, adding that the only group that benefits from aspirin and LMWH are women with acquired thrombophilia antiphospholipid syndrome.

ALIFE2 was an investigator-initiated trial that from 2012 to 2021 randomized 326 pregnant women with two or more miscarriages and inherited thrombophilia to standard care with or without LMWH (enoxaparin 40 mg, dalteparin 5,000 IU, tinzaparin 4,500 IU, or nadroparin 3,800 IU). Aspirin was also used in 11% of patients.

Participants had to be enrolled at gestational age of 7 weeks or earlier. Overall, more than 10,000 women were screened for inclusion over the 9-year study period at 41 centers in five countries (the Netherlands, U.S., U.K., Slovenia, and Belgium), with most women excluded for not having confirmed inherited thrombophilia.

The primary endpoint was live birth rate, with secondary endpoints including miscarriage and adverse obstetric outcomes. Safety outcomes included bleeding episodes, thrombocytopenia, skin reactions, and neonatal congenital malformations.

Average patient age was 33-34 years, most were white, and 70% of the women in each arm had experienced three or more prior miscarriages. The most common thrombophilia types were heterozygosity for factor V Leiden (55-58%), prothrombin 20210A mutation (24-27%), and protein S deficiency (13-14%), while 3.6% had combined thrombophilia.

The OR for the primary endpoint adjusted for differences in baseline characteristics, including maternal age, number of miscarriages, type of center, and country.

Souce: medscape

A Rare Disease That’s More Common Than You Think .

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When people think of blood clotting disorders, Factor V (“Five”) Leiden isn’t the first one that comes to mind. But it could be more common than you think.

As many as 3-8 percent of all people who have European roots carry the gene mutation, and it is the most common inherited blood clotting disorder, also known as thrombophilia. It is rare in African-Americans and Asians.

With Factor V Leiden thrombophilia, your blood has a tendency to form abnormal blood clots that can block your blood vessels. Though Factor V Leiden doesn’t automatically cause blood clots, it does increase any existing risk factors you already have. There are many risk factors but the more common ones include cancer, prolonged immobilization, following surgery, pregnancy, hormone therapy, injury or trauma. Anyone who has increased risk factors should talk with their doctor about how to improve their odds to keep healthy blood flowing smoothly.

Select few experience blood clot symptoms

Your blood has substances in it that help you stop bleeding when you cut yourself or you get injured. These substances are not supposed to clump up in the arteries or the veins under normal circumstances, though. The faulty gene in Factor V Leiden increases the likelihood that clots can form in blood vessels where they are not wanted.

Blood clots that form in blood vessels can be dangerous when they block blood flow to the legs (deep venous thrombosis) or break off and travel to the lungs where they can cause a pulmonary embolism, a medical emergency.

Not all people who have Factor V Leiden develop blood clots. In fact, only 10 percent of all those with the disorder ever experience any blood clotting problems.

blood clot

Reducing your risk

John R. Bartholomew, MD, Section Head of Vascular Medicine and Director of the Thrombosis Center at Cleveland Clinic, says that patients should keep news about the mysterious-sounding disorder in perspective. “Factor V Leiden is a relatively uncommon condition even among the population group most often affected by it,” he said.

Though you are unlikely to have the pair of genes that cause Factor V Leiden, it’s always a good idea to assess your risk factor for cardiovascular problems.

Some things that increase your risk for blood clots are beyond your control, such as recovering from surgery, having certain diseases or being injured, but other risk factors are within your control.

Dr. Bartholomew says, “Everyone should act to eliminate any risk factors that are under their control, namely quitting smoking, losing weight, and being physically active. This is especially important for patients who have thrombophilia. They should also notify all of their doctors if they have this condition.”

Factor V Leiden provides a good reminder to people to pay attention to the risk of blood clots, and how important it is to help avoid them by changing some bad habits, exchanging them for healthy ones instead.