PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

New approach prevents thrombosis without increasing the risk of bleeding

2014-02-06
(Press-News.org) Contact information: Press Office
pressinfo@ki.se
46-852-486-077
Karolinska Institutet
New approach prevents thrombosis without increasing the risk of bleeding In collaboration with an international team, researchers at Karolinska Institutet in Sweden have developed an antibody, 3F7, which blocks a protein that is active in the coagulation system factor XII. Inhibition of factor XII makes it possible to prevent thrombosis in blood vessels without increasing the risk of bleeding in clinical settings.

Thrombosis is caused by blood clotting; clots can block blood flow in one or more blood vessels and so cause thrombotic diseases such as stroke, myocardial infarction or pulmonary embolism. Today, thrombosis is prevented or treated by means of anticoagulants. There is a broad variety of anticoagulant drugs, such as warfarin (a vitamin K inhibitor), the novel oral anticoagulants (dabigatran or rivaroxaban) and drugs of the heparin group. All of these agents target different components of the blood coagulation system to prevent blood from clotting and thus to interfere with thrombosis. However, all these drugs also entail an increased risk of bleeding in patients that partially offsets their beneficial effects.

The blocking of coagulation factor XII (F XII) functions differently compared to traditional anticoagulants. It has been known for long time that humans that are deficient in FXII do not bleed excessively and because of that FXII was believed to have no function for blood coagulation in patients. In 2005, Thomas Renné and his research team discovered that mice lacking F XII could have neither a stroke nor pulmonary embolism, even though they had normal bleeding patterns.

"Since then, our goal has been to find an effective way to block F XII. Now, we have developed an antibody that blocks F XII in human blood, mice and rabbits", says Thomas Renné. "This provides protection against thrombosis without increasing the risk of bleeding."

Together with the doctoral student Magnus Larsson, the researchers developed and tested the antibody, called 3F7, in rabbits during an ECMO treatment. ECMO is an advanced heart-lung machine used in life-threatening conditions especially in infants. Contact with the plastic tubing causes the blood to clot, so patients are routinely administered with anticoagulants (heparin). However due to the heparin anticoagulation patients bleed excessively and a substantial number even dies from these bleedings.

In the study, thrombosis in rabbits on ECMO receiving 3F7 decreased was as low as rabbits receiving heparin, but the risk of bleeding with 3F7 was minimal, whereas heparin-treatment led to bleeding.

"Blocking F XII appears to be an effective strategy against thrombus formation, and we have shown this in experiments on rabbits in a clinically relevant context", says Thomas Renné. "There is a great need for a treatment that reduces the clot risk in emergency situations, such as during ECMO treatment and many others such as cardiovascular surgery. We plan to test the antibody in a phase I study. It is possible that the antibody also blocks inflammation mediated by F XII, an interesting area for future studies."

### The study was funded by Swedish Heart-Lung Foundation, Stockholm County Council (ALF), the Swedish Cancer Society, HRH Crown Princess Lovisa's Association for Child Medical Care, the Swedish Research Council, the German Research Society and the European Research Council. Several of those involved in the study are employees of the pharmaceutical company CSL Behring, which has consequently contributed to the study's inception.

Publication: 'A Factor XIIa Inhibitory Antibody Provides Thromboprotection in Extracorporeal Circulation Without Increasing Bleeding Risk', Magnus Larsson, Veronika Rayzman, Msarc W. Nolte, Katrin F. Nickel, Jenny Björkqvist, Anne Jämsä, Matthew P. Hardy, Marion Fries, Stefan Schmidbauer, Patricia Hedenqvist, Michael Broomé, Ingo Pragst, Gerhard Dickneite, Michael J. Wilson, Andrew D. Nash, Con Panousis and Thomas Renné, Science Translational Medicine, 5 February 2014 Vol 6 Issue 222 222ra17.

Contact the Press Office and download images: http://ki.se/pressroom

Website of the journal: http://stm.sciencemag.org/

Karolinska Institutet - a medical university: http://ki.se/english


ELSE PRESS RELEASES FROM THIS DATE:

Some receive unnecessary prioritization for liver transplantation, says Penn Medicine study

2014-02-06
(PHILADELPHIA) – Patients waiting for liver transplants ...

New analysis of endometriosis could help diagnoses, treatments

2014-02-06
CAMBRIDGE, MA -- Endometriosis, the invasive displacement of uterine tissue into surrounding organs, affects at least 10 percent of women. The disease, which is often misdiagnosed, can cause ...

Female mice prefer unfamiliar male songs

2014-02-06
Female mice prefer songs of mice that are different from their parents when selecting a mate, according to a study published February 5, 2014 in PLOS ONE by Akari Asaba from the Azabu University, ...

Mass extinction may not cause all organisms to 'shrink'

2014-02-06
The sizes of organisms following mass extinction events may vary more than previously thought, which may be inconsistent with the predictions of the so-called ...

Tree roots in the mountains 'acted like a thermostat' for millions of years

2014-02-06
For the first time, scientists have discovered how tree roots in the mountains may play an important role in controlling long-term global temperatures. Researchers from Oxford ...

New stem cell research removes reliance on human and animal cells

2014-02-06
A new study, published today in the journal Applied Materials & Interfaces, has found a new method for growing human embryonic stem cells, that doesn't rely on supporting human or animal cells. Traditionally, ...

Study shows yogurt consumption reduces the risk of type 2 diabetes

2014-02-06
New research published in Diabetologia (the journal of the European Association for the Study of Diabetes) shows that higher consumption of yoghurt, compared with no consumption, can reduce ...

Scientists create potential vaccine ingredient for childhood respiratory disease

2014-02-06
LA JOLLA, CA—February 5, 2014—Scientists at The ...

Social media analysis shows the Garment District still rules New York fashion

2014-02-06
A new study shows New York fashion designers don't just flock ...

Quarks in the looking glass

2014-02-06
From matching wings on butterflies to the repeating six-point pattern of snowflakes, symmetries echo through nature, even down to the smallest building blocks of matter. Since the discovery of quarks, the building ...

LAST 30 PRESS RELEASES:

KAIST Develops Retinal Therapy to Restore Lost Vision​

Adipocyte-hepatocyte signaling mechanism uncovered in endoplasmic reticulum stress response

Mammals were adapting from life in the trees to living on the ground before dinosaur-killing asteroid

Low LDL cholesterol levels linked to reduced risk of dementia

Thickening of the eye’s retina associated with greater risk and severity of postoperative delirium in older patients

Almost one in ten people surveyed report having been harmed by the NHS in the last three years

Enhancing light control with complex frequency excitations

New research finds novel drug target for acute myeloid leukemia, bringing hope for cancer patients

New insight into factors associated with a common disease among dogs and humans

Illuminating single atoms for sustainable propylene production

New study finds Rocky Mountain snow contamination

Study examines lactation in critically ill patients

UVA Engineering Dean Jennifer West earns AIMBE’s 2025 Pierre Galletti Award

Doubling down on metasurfaces

New Cedars-Sinai study shows how specialized diet can improve gut disorders

Making moves and hitting the breaks: Owl journeys surprise researchers in western Montana

PKU Scientists simulate the origin and evolution of the North Atlantic Oscillation

ICRAFT breakthrough: Unlocking A20’s dual role in cancer immunotherapy

How VR technology is changing the game for Alzheimer’s disease

A borrowed bacterial gene allowed some marine diatoms to live on a seaweed diet

Balance between two competing nerve proteins deters symptoms of autism in mice

Use of antifungals in agriculture may increase resistance in an infectious yeast

Awareness grows of cancer risk from alcohol consumption, survey finds

The experts that can outsmart optical illusions

Pregnancy may reduce long COVID risk

Scientists uncover novel immune mechanism in wheat tandem kinase

Three University of Virginia Engineering faculty elected as AAAS Fellows

Unintentional drug overdoses take a toll across the U.S. unequally, study finds

A step toward plant-based gelatin

ECMWF unveils groundbreaking ML tool for enhanced fire prediction

[Press-News.org] New approach prevents thrombosis without increasing the risk of bleeding