Tag: heparin

Categories : Immune System Obstetrics & GynaecologyTags :

New Treatment for Pregnancy Loss Caused by Specific Autoantibody

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Amongst women who experience recurrent pregnancy loss, around 20% test positive for a specific autoantibody. A Kobe University-led research team now found a treatment using either of two common drugs that drastically increases these women’s chances of carrying to full-term without complications, reporting their findings in Frontiers in Immunology.

Recurrent pregnancy loss is a condition of women who have lost two or more pregnancies for non-obvious reasons. Kobe University obstetrician Tanimura Kenji and his team have previously found that in 20% of these women, they can detect a specific antibody in their blood that targets their own bodies: anti-β2-glycoprotein I/HLA-DR autoantibodies.

Tanimura explains: “There is no known treatment for this particular condition, but the antibodies have a similar target to those that play a role in a different condition that has an established treatment.” Therefore, he wanted to test whether that treatment also works in the cases with the newly discovered antibody.

Tanimura enlisted the help of obstetricians across five hospitals in Japan and over the course of two years analysed the blood of consenting women suffering from recurrent pregnancy loss for the antibodies. If any of these women got pregnant during this time frame, their doctors would offer treatment options also containing those drugs that are effective against the chemically similar condition, specifically, low-dose aspirin or heparin. The research team then observed how many of the women who included these drugs in their treatment had full-term live births or pregnancy complications and compared that to the pregnancy outcomes in women who did not take either of the two drugs.

They report that women who received the treatment were much more likely to have live births (87% did) compared to the ones without treatment (of which only 50% had live births). In addition, amongst the live births, the treatment reduced the likelihood of complications from 50% to 6%. “The sample size was rather small (39 women received the treatment and 8 did not), but the results still clearly show that a treatment with low-dose aspirin or heparin is very effective in preventing pregnancy loss or complications also in women who have these newly discovered self-targeting antibodies,” summarises Tanimura.

Many women who tested positive for the newly discovered self-targeting antibodies also tested positive for the previously known ones. However, the Kobe University-led team found that women who only had the newly discovered antibodies and who received the treatment were even more likely to have a live birth (93%) and, amongst these, none had pregnancy complications.

Looking ahead, Tanimura says: “The newly discovered self-targeting antibody has been demonstrated to be involved also in infertility and recurrent implantation failure, as well as a risk factor for arterial thrombosis in women with systemic rheumatic diseases. I therefore expect that studies about the effectivity of the treatment against a broader range of conditions might produce encouraging results.”

Source: Kobe University

Categories : Obstetrics & GynaecologyTags :

Researchers Advise Stopping Heparin Use for Pregnant Women with Thrombophilia and Miscarriage Risk

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Heparin, commonly prescribed to pregnant women with an inheritable blood clotting condition and a history of recurrent miscarriage does not help to reduce their miscarriage risk, new research has found. The UK-led international study was published in The Lancet.

Researchers are now advising doctors to stop offering the anticoagulant heparin to women and birthing people with inherited thrombophilia, an inherited condition which increase clotting risk.

Despite the lack of evidence and guidance, doctors often prescribe heparin to women with recurrent miscarriage and inherited thrombophilia. It’s costly for health services, and inconvenient for women who must inject the drug daily and are more likely to experience bruising as a result.

The results show that a daily injection of heparin does not improve the chance of a live birth for women who have previously had two or more miscarriages and confirmed inherited thrombophilia, when compared to standard care.

Led by Professor Siobhan Quenby at the University of Warwick, the ALIFE2 trial recruited women from 40 hospitals in Europe and the US.

326 women with inherited thrombophilia and recurrent miscarriage were split into 2 groups; 164 received heparin across the course of their pregnancy, starting from as soon as possible after a positive pregnancy test and ending at the start of labour. 162 were not offered the medication.

All women received standard obstetrician-led care and all women were encouraged to take folic acid.

The rate of live births for each group was roughly the same: 116 women (71.6%) treated with heparin had a baby born alive after 24 weeks’ pregnancy. 112 women (70.9%) in the standard care group had a baby born alive after 24 weeks’ pregnancy.

The risk of other pregnancy complications, including miscarriage, babies with low birth weight, placental abruption, premature birth or pre-eclampsia, was about the same for both groups.

As expected, bruising easily was reported by 73 (45%) of women in the group taking heparin (mostly around injection-sites) and only 16 (10%) in the standard care group.

Professor Siobhan Quenby says, “Based on these findings, we don’t recommend the use of Low Molecular Weight Heparin for women with recurrent pregnancy loss and confirmed inherited thrombophilia.”

“We also suggest that screening for inherited thrombophilia in women with recurrent pregnancy loss is not needed. Patients and doctors will always value knowing about any factor which could be associated with recurrent miscarriage, but the association between inherited thrombophilia and recurrent miscarriage isn’t proven: a recent review of research showed that thrombophilia is as common in the general population as it is in women with recurrent miscarriage.”

“Many women with recurrent miscarriage around the world are tested for inherited thrombophilia and are treated with heparin daily. Research now shows that this screening is not needed, the treatment isn’t effective, and it is giving false hope to many by continuing to offer it as a potential preventive treatment.”

Twenty-eight percent of women who participated in the trial lost their badly wanted pregnancies, and these unexplained losses will be the focus of further study, as our researchers continue to search for answers and treatment to prevent early pregnancy loss.

Source: Medical Xpress

Categories : Emergency Medicine Injury & TraumaTags :

Aspirin as Effective as Heparin for Clot Prevention in Bone Fracture Hospitalisation

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Patients hospitalised with fractures typically receive low-molecular-weight heparin to prevent life-threatening blood clots. A new clinical trial, however, found that inexpensive over-the-counter aspirin is just as effective. The findings, published today in the New England Journal of Medicine, may lead surgeons to change their practice and administer aspirin to these patients.

With more than 12 000 patients, the multi-centre randomised clinical trial is the largest trial ever conducted on orthopaedic trauma patients. This multidisciplinary collaboration between orthopaedic surgeons and trauma surgeons points to the importance of evaluating techniques used to prevent post-surgical complications, like blood clots and infections, through high-quality, head-to-head comparison studies.

“Many patients with fractures will likely strongly prefer to take a daily aspirin over receiving injections after we found that both give them similar outcomes for prevention of the most serious outcomes from blood clots,” said the study’s principal investigator Robert V. O’Toole, MD. “We expect our findings from this large-scale trial to have an important impact on clinical practice that may even alter the standard of care.”

Patients who experience fractures that require surgery are at increased risk of developing blood clots, including life-threatening pulmonary embolisms. Current guidelines recommend prescribing low-molecular-weight heparin (enoxaparin) to prevent these clots, although smaller clinical trials in total joint replacement surgery suggested a potential benefit of aspirin as a less-expensive, widely available option.

The study enrolled 12 211 patients with leg or arm fractures that necessitated surgery or pelvic fractures regardless of the treatment. Half were randomised to 30mg of injectable enoxaparin twice daily. The other half received 81mg of aspirin twice daily. Patients were followed for 90 days to measure health outcomes from the two treatments.

The main finding of the study was that aspirin was “non-inferior,” or no worse than low molecular-weight heparin in preventing death from any cause – 47 patients in the aspirin group died, compared with 45 patients in the heparin group. For other important complications, the researchers also found no differences in pulmonary embolisms between the two groups. The incidence of bleeding complications, infection, wound problems, and other adverse events from the treatments was also similar in both groups.

Of all the outcomes studied, the only potential difference noted was in deep vein thrombosis. This condition was relatively uncommon in both groups as it occurred in 2.5% of patients in the aspirin group, and in 1.7% of patients in the heparin group.

“This relatively small difference was driven by clots lower in the leg, which are thought to be of less clinical significance and often do not require treatment,” said study co-principal investigator Deborah Stein, MD, MPH.

“Many patients don’t like giving themselves injections. It’s not fun in terms of giving the actual injection because it burns, and your stomach tends to bruise more easily compared to aspirin,” said Debra Marvel, a 53-year-old from Columbia, MD, who served as a patient advisor on the study. She received Lovenox (low-molecular-weight heparin) after her legs were crushed in a 2015 pedestrian accident, requiring multiple surgeries at the University of Maryland Shock Trauma Center. “Patients also prefer aspirin because Lovenox can be expensive based on insurance.”

“An estimated one million Americans are hospitalised each year with extremity fractures, and this new finding could help prevent potentially fatal blood clots in these patients using a medication that is cheaper and far easier to administer,” said Mark T. Gladwin, MD, Vice President for Medical Affairs, University of Maryland, Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor and Dean, University of Maryland School of Medicine. “Given these important results, we can expect the guidelines for the prevention of blood clots to be revised to include the option of aspirin for patients with traumatic bone fractures.”

Source: University of Maryland School of Medicine

Categories : Cardiovascular DiseaseTags :

Heparin Combination Extends Half-life to 24 Hours

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Source: CC0

The anticoagulant drug heparin is widely given to patients with blood clotting disorders or after surgery to prevent complications. But it remains difficult to dose correctly, potentially leading to overdosing or underdosing. A team of Penn State researchers combined heparin with a protein fragment, peptide, to slow down the release of the drug and convey the medication directly to the site of a clot. They published their findings in the journal Small.

“We wanted to develop a material that can gradually deliver heparin over time rather than the current iteration that gets cleared from the body in a couple of hours,” said corresponding author Scott Medina, Penn State associate professor of biomedical engineering. “We also wanted to deliver the drug through the skin instead of through an IV.”

When mixed, positively charged peptides and negatively charged heparin bind to create a nanogranular paste that can be injected under the skin, forming a cache of material that is then diffused in the circulatory system and travels to blood clots when they appear. The turbulent flow of fluid near a blood clot triggers the two materials to separate, allowing heparin to begin its anticoagulating action.

“The peptide is ideal for pairing with heparin because it essentially blocks heparin’s action until it is needed in the body,” said Atip Lawanprasert, doctoral student in biomedical engineering and first author on the paper. “The peptide also has some anticoagulating properties on its own: It binds to platelets in the blood, enabling action at the clotting site.”

Without an added bonding agent, heparin applies its anti-clotting properties indiscriminately, not just at blood clot sites, and clears quickly, its half-life only 60 to 90 minutes. Using preclinical animal trials, researchers determined that the addition of peptide allows for a dramatic increase of heparin’s half-life, to up to nearly 24 hours.

“The peptide increases heparin’s effects by more than ten times longer than what is currently being used,” Medina said. “The increased half-life allows for sustained treatments for patients, less medication waste and more accurate dosing. Eventually, this could allow the medication to be injected under the skin just once a day, rather than an all-day IV drip.”

Next, researchers plan to replicate the study in a clinical setting, as well as study the effect of the medication’s toxicity with multi-day administration.

Source: Penn State

Categories : Medical IndustryTags :

A Synthetic Alternative to Pig-derived Heparin

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Scientists have developed a process to synthesise the vital blood thinner heparin, which is normally harvested from pig intestines. This synthetic heparin would help the quality control issues and shortages associated with pig-derived heparin.

The most expensive part of a pig is not a cut of bacon or a chop, but the part of the intestine used to make heparin. About 2000 pigs required to produce a kilogram of heparin, which provides medication to up to 6000 patients. In total, it is estimated that about one billion primarily Chinese food pigs each year also supply intestines for the extraction and processing of heparin.

However, this can cause problems for patients. When making medicines derived from animals, the chemical structure is rarely uniform. There are relatively common but harmless side effects, and in very rare cases severe and life-threatening immune reactions. Additionally, there are ethical and religious concerns for many patients. Bovine- and sheep-derived heparin are also produced but have the same concerns of being of animal origin. In fact, prior to 2000, heparin was derived from cows until the outbreak of mad cow disease.

Therefore, it has long been an ambition among researchers to make heparin in a laboratory to get cleaner heparin without side effects. Now researchers from the Copenhagen Center for Glycomics at the University of Copenhagen are ready with a study that shows that it is possible to make heparin without the use of animals.  which was published in Science Advances.

“By making heparin without the animal, you get a much cleaner and more uniform chemical structure. We show that we can do it in the laboratory, i.e. in a so-called ‘cell factory’, in the same way as many other types of medicine are made. It is a step in the direction of the development that has also happened with insulin, which was previously extracted from the pancreas in pigs before we learned to produce it in the laboratory,” explained Associate Professor Rebecca Miller, who led the study. 

There is already a synthetic alternative to heparin, but it is difficult to dose and can lead to overdose. Because of this, GPs often prescribe pig-derived heparin to their patients.

Heparin is today extracted from pig intestines’ mucosa. Due to the sheer number of patients who need the medicine, the scale of the production is vast, making quality control a recurring problem for manufacturers.

In 2008, a number of stocks of heparin from Chinese pigs were recalled when it was found that the medicine was contaminated. The case ended up costing the lives of more than 100 Americans.

“Of course you want to avoid that, in addition to moving the source from animals to laboratory cells. With our new technology, we have made a design for how to make heparin in a cell that is clean and uniform and it suggests that it has the same medicinal effect as market heparin. In this way, you potentially get a product that leads to neither common nor life-threatening side effects,” said Richard Karlsson, PhD, who has also contributed to the main author of the study.

Right now, the world is facing a shortage of heparin because swine flu has thinned the pig population in China, the largest heparin producer.
Next steps would be to scale up production to provide much larger quantities of the new synthetic heparin. 

Source: University of Copenhagen

Categories : COVIDTags :

High-dose Heparin Reduces Mortality in Moderately-ill COVID Patients

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SARS-CoV-2 viruses (yellow) infecting a human cell. Credit: NIH

A high dose of heparin, an inexpensive and globally available medication, reduces mortality risk in hospitalised, moderately-ill COVID patients, suggests a new study led by St. Michael’s Hospital.

Appearing in the BMJ, the RAPID Trial compared a high, therapeutic dose of heparin to a prophylactic low dose for patients with moderate COVID and elevated d-dimer levels admitted to hospitals. D-dimers are protein fragments produced when a blood clot gets dissolved; higher levels indicate increased clotting risks.

The researchers studied 465 patients in hospitals around the world and found that while the therapeutic dose of heparin was not associated with a significant reduction in the study’s primary outcome, a composite of death, the need for mechanical ventilation or admission to intensive care, the dosing of heparin did reduce all-cause death in moderately-ill COVID patients admitted to hospital by 78%.

“Our study confirms therapeutic heparin is beneficial in patients who are on the ward with COVID, but other studies suggest it could be harmful for patients who are in critical care,” said Dr. Peter Jüni, Director of the Applied Health Research Centre at St. Michael’s and co-lead of the study.

Therapeutic doses of heparin are used for deep vein thrombosis or pulmonary emboli, whereas prophylactic, or lower, doses are used for patients admitted to Internal Medicine wards to prevent blood clotting while they are in hospital.

Several trials have investigated using blood thinners in COVID patients due to heightened inflammation and clotting in blood vessels caused by the virus. Dr. Michelle Sholzberg, Head of the Division of Hematology-Oncology and Director of the Coagulation Lab at St. Michael’s, and co-lead on the study, hopes this research contributes to a change in treatment guidelines for COVID patients.

“This is a once-in-a-million opportunity – heparin is inexpensive, globally available, and exists in every single hospital pharmacy cabinet right now,” she said. “It’s an opportunity to rapidly repurpose a drug available around the world.”

In particular, she said, the treatment could make a difference in areas where vaccine availability or coverage continues to be limited. Heparin is included in the WHO’s list of essential medicines.

The researchers hope to learn more from the data collected by analysing it further to address new questions, and are also considering revisiting patient outcomes to understand whether these therapies reduce the odds of long COVID.

Source: Unity Health

Categories : COVID HospitalsTags :

Heparin Benefit Seen in Moderately Ill COVID Patients

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Photo by Marcelo Leal on Unsplash
Photo by Marcelo Leal on Unsplash

New trial results show that early administration of the blood thinner heparin to moderately ill hospitalised COVID patients with could halt the thrombo-inflammation process, reducing the risk of severe disease and death.

COVID is characterised by inflammation and abnormal clotting in the blood vessels, especially the lungs, and is believed to contribute to progression to severe disease and death. 

The study is available as a preprint on MedRxiv and was led by investigators at St. Michael’s Hospital, a site of Unity Health Toronto, and the University of Vermont’s Larner College of Medicine.

Heparin, an anticoagulant, is indicated for both the prevention and treatment of thrombotic events such as deep vein thrombosis (DVT) and pulmonary embolism as well as atrial fibrillation. Heparin is also used to prevent excess coagulation during procedures such as cardiac surgery, extracorporeal circulation or dialysis. Heparin also has a wide range of off-label uses in hospitals. “This study was designed to detect a difference in the primary outcome that included ICU transfer, mechanical ventilation or death,” said study co-principal investigator  Mary Cushman, MD, MSc, professor of medicine at the UVM Larner College of Medicine.
The open-label randomised international multi-centre clinical RAPID Trial (also known as the RAPID COVID COAG – RAPID Trial) examined the benefits of administering a therapeutic full dose of heparin versus a prophylactic low dose to hospitalised patients with moderate COVID.

The primary outcome was a composite of ICU admission, mechanical ventilation, or death up to 28 days. Safety outcomes included major bleeding. Primary outcome occurred in 16.2% of patients with therapeutic full dose heparin, and 21.9% with low dose heparin (odds ratio [OR], 0.69). Four patients (1.8%) with therapeutic heparin died vs 7.6% with prophylactic heparin (OR, 0.22).

“While we found that therapeutic heparin didn’t statistically significantly lower incidence of the primary composite of death, mechanical ventilation or ICU admission compared with low dose heparin, the odds of all-cause death were significantly reduced by 78 percent with therapeutic heparin,” said first author and co-principal investigator Michelle Sholzberg, MDCM, MSc, Head of Division of Hematology-Oncology, medical director of the Coagulation Laboratory at St. Michael’s Hospital of Unity Health Toronto, and assistant professor at the University of Toronto.

Co-principal investigator Peter Jüni, MD, director of the Applied Health Research Centre (AHRC) at St. Michael’s, and professor of medicine at the University of Toronto, said that the researchers also presented a meta-analysis of randomised evidence (including data from a large multiplatform trial of ATTACC, ACTIV-4a and REMAP-CAP), which clearly indicated that therapeutic heparin is beneficial in moderately ill hospitalised COVID patients. He added that an additional meta-analysis presented in the preprint showed that therapeutic heparin is beneficial in moderately ill hospitalised patients but not in severely ill ICU patients.

Unusually, the RAPID Trial was funded through grassroots efforts from various institutions, grants and even a GoFundMe campaign.

“We called this trial ‘The Little Engine that Could,’ because of the sheer will of investigators around the world to conduct it,” said Cushman.

Sholzberg said, “We believe that the findings of our trial and the multiplatform trial taken together should result in a change in clinical practice for moderately ill ward patients with COVID.”

Source: University of Vermont

Journal information: Michelle Sholzberg et al, Heparin for Moderately Ill Patients with Covid-19, MedRxiv (2021). DOI: 10.1101/2021.07.08.21259351