Deep vein thrombosis is a dangerous yet preventable condition. Conventional treatment poses a serious risk of bleeding, but a new study offers hope for a different therapeutic approach and prevention strategy.
The Centers for Disease Control and Prevention (CDC) report that up to 900,000 people in the United States live with deep vein thrombosis (DVT) and pulmonary embolism (PE). It is also estimated that between 60,000 and 100,000 U.S. individuals die from DVT/PE.
DVT occurs when a blood clot arises in a deep vein - usually in the lower legs or thighs. If the blood clot dislocates, it can travel all the way to the lungs, triggering PE. Approximately 25 percent of PE cases result in sudden death.
Currently available medication for DVT/PE includes anti-blood-clotting drugs such as heparin and warfarin. Although generally effective, these drugs increase the risk of bleeding.
However, new research suggests that common allergy medication could be used in combination with conventional anticoagulants to treat DVT. By targeting the body's so-called mast cells, which are immune cells involved in vasodilation and vascular homeostasis, this new approach may bypass the side effects normally associated with anticoagulant treatment alone.
The new study was carried out by a team of researchers led by Dr. Alexander Brill, of the Institute of Cardiovascular Sciences at the University of Birmingham in the United Kingdom, and the findings were published in the journal Circulation Research.
Dr. Brill's previous work has investigated the role of mast cells in the prevention of DVT.
Finding an alternative to anticoagulants
The reason that common anti-clotting medication causes bleeding is that it works by affecting the body's hemostasis - that is, its natural reaction to injury or bleeding.
Hemostasis is the reason that we do not bleed to death from a cut; the body's blood coagulation system enables a helpful form of clotting that stops the bleeding. But anti-clotting medication affects this process.
The new research focused on finding a DVT treatment that circumvents the body's natural blood coagulation system. Seeking to investigate whether mast cells do have a role in triggering DVT, Dr. Brill and his colleagues designed a mouse model wherein they silenced the gene involved in the formation of mast cells.
Additionally, the researchers surgically induced DVT by partially closing off a blood vessel called the inferior vena cava.
Mast cell deficiency prevents DVT
The study found that "two strains of mice deficient for [mast cells] were completely protected from DVT." Importantly, the study also revealed that mice whose mast cells genes were turned off had normal hemostasis. This completely bypassed the bleeding risks usually involved in the use of anti-clotting medication.
The findings were deemed surprising by the lead researcher, who told Medical News Today that mast cell deficiency was expected to have the opposite effect.
He says, "[W]e were surprised by the findings because mast cells contain the strongest natural anticoagulants [heparin] and we expected that depletion of mast cells would result in a prothrombotic effect."
"These findings offer new hope for the treatment of [DVT] without a risk of bleeding. If further human studies support our findings in mice, drugs to block mast cell production could be used in the future alongside lower doses of anticoagulants such as warfarin, significantly reducing bleeding risk."
Dr. Alexander Brill
Allergy drugs may be the answer
Mast cell inhibitors are already being used to treat allergic diseases such as bronchial asthma or allergic conjunctivitis, which is also known as hay fever. And, the fact that these drugs are already approved and in use means that they could be quickly tested in human trials and made available to the public.
"This is particularly exciting because [...] this discovery could help people with DVT sooner rather than later," says Dr. Brill.
Speaking to MNT about the strengths and limitations of the research, Dr. Brill commented, "The main strength of the study is that we were able to prevent DVT using a "backdoor" - the immune system that has no implication in normal hemostasis and therefore targeting it is not supposed to be accompanied by any bleeding complications."
However, "the study [...] was performed on a murine model and its relevance to [the] human situation should be further proven," he noted.
As a next step, the researchers hope to see whether targeting mast cells has the same effect in humans. If it does, human clinical trials should follow, testing whether mast cell membrane stabilizers are an effective prevention strategy for DVT.