Deep Vein Thrombosis (DVT)

The University of Oklahoma, ScienceDaily.com  —  A worldwide research consortium that includes the University of Oklahoma Health Sciences Center has proven that a new drug is more effective and easier to use than current medicines in the prevention of blood clots following hip replacement surgery.

The results reveal a better way to prevent the formation of blood clots in the deep veins of the legs — a condition known as deep vein thrombosis (DVT). The blood clots become life-threatening pulmonary embolisms (PE) when they break free and travel to the lungs.

Gary Raskob, Ph.D., an internationally recognized DVT expert and dean of the OU College of Public Health, was co-author and a co-director of the study, which appeared in The New England Journal of Medicine. The study compared the drug Apixaban, given orally twice a day, to the current standard medicine, Enoxaparin, given twice daily by injection under the skin.

The randomized, double-blind trial involved more than 5,000 patients and showed Apixaban reduced the risk of blood clots, without increasing bleeding side effects.

“Each year, about 750,000 Americans undergo hip or knee replacement surgery and that number is growing rapidly. This is a major stride forward as we work toward better prevention of life-threatening blood clots in these patients,” Raskob said.

He added that the development of new oral anticoagulant agents, like Apixaban, has raised hope of a standard of care for DVT prevention that is as effective as or more effective than current standard approaches as well as being equally safe and more convenient for patients.

Raskob also was a primary author in another study published in the same issue of The New England Journal of Medicine focusing on the treatment of patients with established deep vein thrombosis.

“Despite the best current prevention efforts, blood clots still occur. So, it is important to continue to work toward better treatments as well as better ways to prevent blood clots,” he said.

The second clinical trial, which included patients at the University of Oklahoma Health Sciences Center, found that the medication Rivaroxaban provided a simple, effective, single-drug approach for both short-term and continued long-term treatment of patients with deep vein thrombosis. Rivaroxaban is given orally in a fixed dose without the need for laboratory blood testing to monitor the anti-clotting effect. Current treatment methods, on the other hand, use two drugs, one given by injections under the skin once or twice a day for 5 to 10 days, followed by an oral medication that requires careful monitoring and dose adjustment based on results of regular blood tests.

“We are excited to have been able to participate in a study that is helping to advance the way we care for patients with deep vein thrombosis,” said Suman Rathbun, M.D., a vascular medicine specialist at the OU Vascular Center. “Prevention is paramount, but we are not yet able to prevent 100 percent of these blood clots. So, it is important for us to continue to work toward new and improved treatments as well.”

Scientists at OU and their colleagues worldwide are working diligently to find better and more practical tools to prevent and treat blood clots in the legs and lungs.

DVT affects at least 300,000 Americans each year. Most deep-vein blood clots occur in the lower leg or thigh. These blood clots can break off and travel through the bloodstream. When a clot travels to the lungs, the condition is called pulmonary embolism (PE), a serious condition that can cause damage to the lungs and death.

Researchers stress that while the results of the research are encouraging, the medications studied are not yet approved by the U.S. Food and Drug Administration. The studies were funded by Bristol-Myers Squibb, Pfizer, Bayer Schering Pharma and Ortho-McNeil.

Symptoms of DVT and PE

DVT (Deep Vein Thrombosis)

A DVT is a blood clot that most commonly occurs in the leg, typically only one leg (image 1). However, occasionally it occurs in both legs at the same time (=bilateral DVT). Sometimes, a DVT is in the pelvic veins or the big abdominal vein (=inferior vena cava). And some DVTs occur in the arm. The anatomy and terminology of leg, pelvic and arm veins (together called “venous clot” or “venous thromboembolism=VTE) is also discussed here.

Image 1. DVT in right leg; clot broken off the DVT and travelling in the big abdominal vein towards the lung; PE in the right lung (Graphic design Jeff Harrison, Wilmington, NC; © Stephan Moll)

Symptoms range from no symptoms whatsoever, to barely noticeable, to severe. Symptoms may be in the foot, ankle and calf, or involve the whole leg. Similarly, in the case of arm DVT, the symptoms may involve only the forearm, or also include the upper arm. They occur not just for a few seconds or minutes, but for hours or days. The classic symptoms of an acute DVT are:

  • Pain
  • Swelling
  • Discoloration (bluish, slightly purplish or reddish)
  • Patients may also have lower back pain, if the clot is in the veins in the pelvic area or abdominal vein (= inferior vena cava = IVC).

Superficial clot (superficial thrombophlebitis) and postthrombotic syndrome

Not typical for DVT is when a patient has tenderness, pain, swelling, redness, or warmth in just one clearly defined, focal area, when the skin is exquisitely tender and the pain feels like it is right in the skin, or when the patient is able to feel a clot or a firm cord. Those symptoms suggest a superficial clot (=superficial thrombophlebitis). The symptoms of a chronic/old DVT –  a condition also called “postthrombotic syndrome”  – will be explained in a separate blog entry.

PE (Pulmonary Embolism)

A PE is a blood clot in the blood vessels in the lung (images 1-3). The terminology can be confusing and misleading: Arteries are defined as blood vessels that lead away from the heart, veins as vessels that lead blood back to the heart. DVTs occur in veins. Because of the way that the lung is anatomically built into our circulatory system, the vessels leading from the heart into the lung are called arteries, even though the structure of these vessels is much more like that of veins. In addition, clots breaking off from DVTs in the veins of the legs, pelvis or arms, travel in the blood stream towards the heart, through the right heart chamber and then into the lung arteries (=pulmonary arteries), where they get lodged. So even though these clots are in the vessels called pulmonary arteries, they are really considered vein clots. DVT and PE are refered to as venous thromboembolism (VTE), reflecting, that both are really vein clots.

Symptoms of PE also range from no symptoms whatsoever, to barely noticeable, to severe, depnding on how big the clot is (images 2,3). In the most severe case, a massive PE can lead to instant death. Very small PEs fairly commonly occur in patients with DVT and lead to no symptoms whatsoever. The classic symptoms of an acute PE are listed below. They occur not just for a few seconds or minutes, but for hours or days.

  • Chest pain, particularly when taking a deep breath in
  • Shortness of breath
  • Unexplained cough (sometimes coughing up of blood)
  • Unexplained heart racing or pounding
  • Passing out / loosing consciousness

Image 2. Small PE in the left lung. The clot leads to diminished blood flow to that area of the lung, resulting in damaged tissue (=infarct). This results in diminished oxygen uptake into the blood stream and, thus, shortness of breath. The lung surface of that area gets inflammed (=pleuritis), leading to chest pain, particularly on taking a deep breath in. Pleuritis also leads to lung irritation and cough (Graphic design: Jeff Harrison; © Stephan Moll)

 

Subtle Symptoms

Symptoms of DVT and PE (collectively known as VTE = venous thromboembolism) can be subtle and may be confused with other medical conditions. In the case of a DVT, this may be a twisted ankle, Charley horse, muscle tear, sore muscle. In the case of PE this may be a touch of pneumonia, new onset of asthma, inflammation of the joints of the breast bone or ribs (=osteochondritis”). Therefore, a wrong or delayed diagnosis is not uncommon in patients who eventually get diagnosed with DVT or PE. It is good for everybody to know the classical symptoms of DVT and PE, as well as the risk factors. If subtle symptoms occur in the person who has striking risk factors for DVT or PE, this raises the suspicion that this person may truly have a DVT or PE. Appropriate imaging studies (Doppler ultrasound to look for a DVT; CT scan of the chest or a nuclear medicine study called VQ scan).

Risk factors for DVT and PE:

Immobility

  • Hospitalization
  • Stroke resulting in bedridden state or chronic wheelchair use
  • Prolonged sitting

Surgery and Trauma

  • Major surgery (pelvis abdomen, hip, knee)
  • Bone fracture or case
  • Catheter in big vein

Increased Estrogens

  • Birth control pill, patch or ring
  • Pregnancy, for up to 6 weeks after giving birth
  • Hormone therapy

Medical Conditions

  • Cancer and its treatment
  • Heart failure

Other Risk Factors

  • Previous blood clot
  • Family history of clots
  • Clotting disorders
  • Obesity
  • Smoking

 

Image 3. Very large PE. This leads to no blood flow to the lung and to sudden death. (Graphic design Jeff Harrison; copyright Stephan Moll)

American Heart Association, March 21, 2011  —  Researchers have shown for the first time that stem cells injected into enlarged hearts reduced heart size, reduced scar tissue and improved function to injured heart areas, according to a small trial published in Circulation Research: Journal of the American Heart Association.

 

Researchers said that while this research is in the early stages, the findings are promising for the more than five million Americans who have enlarged hearts due to damage sustained from heart attacks. These patients can suffer premature death, have major disability and experience frequent hospitalizations. Options for treatment are limited to lifelong medications and major medical interventions, such as heart transplantation, according to Joshua M. Hare, M.D., the study’s senior author and professor of medicine and director of the Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, University of Miami in Miami, Fla.

 

Using catheters, researchers injected stem cells derived from the patient’s own bone marrow into the hearts of eight men (average age 57) with chronically enlarged, low-functioning hearts.

 

“The injections first improved function in the damaged area of the heart and then led to a reduction in the size of the heart. This was associated with a reduction in scar size. The effects lasted for a year after the injections, which was the full duration of the study,” Hare said.

 

Specifically, researchers found:

Heart size decreased an average of 15 percent to 20 percent, which is about three times what is possible with current medical therapies.

Scar tissue decreased by an average of 18.3 percent.

And there was dramatic improvement in the function, or contraction, of specific heart areas that were damaged.

“This therapy improved even old cardiac injuries,” Hare said. “Some of the patients had damage to their hearts from heart attacks as long as 11 years before treatment.”

 

The researchers had used two different types of bone marrow stem cells in their study — mononuclear or mesenchymal stem cells. The study lacked the power to determine if one type of cell works better than the other. All patients in the study benefited from the therapy and tolerated the injections with no serious adverse events.

 

Hare’s study assessed the effect of stem cell injections differently from other studies of post-heart attack stem cell treatment. His team measured contractility, scar size and structural changes of the heart.

 

“Studies of bone marrow cell therapy for ischemic heart disease in animals have shown improved ejection fraction (the amount of blood the heart can pump). However, this measurement has not reliably translated to early phase studies in humans,” Hare said. “Ejection fraction may not be the best way to measure the success of stem cell therapy in the human heart.”

 

Hare also said their findings suggest that patients’ quality of life could improve as the result of this therapy because the heart is a more normal size and is better functioning. “But, we have yet to prove this clinical benefit — this is an experimental therapy in phase one studies. These findings support further clinical trials and give us hope that we can help people with enlarged hearts.”

 

Co-authors are Adam R. Williams, M.D.; Barry Trachtenberg, M.D.; Darcy L. Velazquez, R.N., B.S.N.; Ian McNiece, Ph.D.; Peter Altman, Ph.D.; Didier Rouy, M.D., Ph.D.; Adam M. Mendizabal, M.S.; Pradip M. Pattany, Ph.D.; Gustavo A. Lopera, M.D.; Joel Fishman, M.D., Ph.D.; Juan P. Zambrano, M.D. and Alan W. Heldman M.D. Author disclosures are on the manuscript.

 

The University of Miami Interdisciplinary Stem Cell Institute, BioCardia (makers of the catheter used) and the National Institutes of Health funded the study.

 

Journal Reference:

1.                       Adam R. Williams, Barry Trachtenberg, Darcy L. Velazquez, Ian McNiece, Peter Altman, Didier Rouy, Adam M. Mendizabal, Pradip M. Pattany, Gustavo A. Lopera, Joel Fishman, Juan P. Zambrano, Alan W. Heldman, and Joshua M. Hare. Intramyocardial Stem Cell Injection in Patients With Ischemic Cardiomyopathy: Functional Recovery and Reverse Remodeling. Circulation Research, March 17, 2011 DOI: 10.1161/CIRCRESAHA.111.242610

University of Reading, in Reading-Berkshire, England

 

 

University of Reading, March 21, 2011) — Scientists from the University of Reading have announced a breakthrough in understanding how to control blood clotting which could lead to the development of new treatments and save the lives of thousands of people each year.

 

Doctors have known for some time that high levels of blood cholesterol can increase the risk of suffering from a heart attack or a stroke. Controlling cholesterol levels has therefore become an important way to reduce the risk of these serious diseases. This has led to the development of drugs that control the function of a protein within our bodies called LXR which regulates cholesterol.

However, researchers from the School of Biological Sciences have discovered that this protein has a double life.

The protein also appears to be involved in inhibiting the function of blood cells known as platelets, a role that is unconnected to cholesterol levels but which results in reducing the blood clotting response. In the research blood clot formation was inhibited by 40%.

Drugs that target LXR may therefore have benefit in reducing cardiovascular disease for two separate reasons: preventing thrombosis, and controlling cholesterol levels.

Professor Jon Gibbins, Director of the University’s Institute for Cardiovascular and Metabolic Research, said: “While blood clotting is essential to prevent bleeding, inappropriate clotting within the circulation, known as thrombosis, is the trigger for heart attacks and strokes — which kill more people in the UK each year than any other disease.”

The study was funded by the British Heart Foundation and Heart Research UK. Researchers found that targeting the LXR protein with anti-thrombotic drugs in mice reduced the size and stability of blood clots (thrombi). The treatment allowed initial thrombi to form (a physiological process necessary to prevent bleeding after injury to blood vessels) but reduced by approximately 40% the stability of the thrombi, preventing clots blocking blood vessels.

Professor Jeremy Pearson, Associate Medical Director at the British Heart Foundation, said: “Both anti-clotting and cholesterol-lowering drugs are vital in reducing the chance of a heart attack or stroke in high-risk patients, but are not always effective and don’t suit all patients because of the risk of side-effects.

“This exciting discovery by Professor Gibbins’ team shows that drugs which lower cholesterol through targeting LXR protein can also reduce harmful blood clotting — potentially opening up paths towards new, more effective treatments.”

 

Journal Reference:

1.                       M. Spyridon, L. A. Moraes, C. I. Jones, T. Sage, P. Sasikumar, G. Bucci, J. M. Gibbins. LXR as a novel anti-thrombotic target. Blood, 2011; DOI: 10.1182/blood-2010-09-306142

 

By Patrick Fuller

March 21, 2011 — Shaken by its worst disaster in recent memory, Japan is battling to restore the hope for a shocked and vulnerable population, including hundreds of thousands crowded into evacuation centers, and slowly get back on its feet despite daunting obstacles.

In many respects, the March 11 earthquake and tsunami in Japan’s northeast is rapidly becoming a disaster associated with the elderly. The three evacuation centers in the shattered town of Otsuchi are filled with the old and ill. Many are too tired or too sick to do little but lie on mattresses on the floor, swathed in blankets.

The weather is taking a heavy toll on the health of the survivors in evacuation centers, many of whom are elderly. Japanese Red Cross Society doctors say there has been an increase in cases of influenza and some diarrheal diseases.

Takanori Watanabe, a Red Cross doctor from Himeji, in western Japan, arrived in Otsuchi as part of a 12-person mobile medical team which runs daily clinics around the evacuation centers.

Friday the team was based in the infirmary of Otsuchi High School, where about 700 people filled the floor space of the school’s gymnasium. The infirmary’s only two beds are being used by an elderly woman who is barely conscious and an old man attached to an I/V drip who is badly dehydrated. Most of the patients coming to the clinic are elderly and many have lost their daily medication in the disaster.

“There are a lot of people with chronic conditions and today, it’s cold so some people have fallen ill,” Dr. Watanabe said. “We’ve had a bad stomach virus going around so a lot of people are getting diarrhea and becoming dehydrated. The Red Cross teams have a limited variety of medicine and since supplies are limited patients are getting just three-day’s supply.’

Another member of Dr. Watanabe’s team, who is trained in emotional counseling, sits in the corner, quietly comforting a teenage girl who has her head in her hands and is sobbing. Everyone in Otsuchi has lost someone. A relative, a friend or a neighbor – the entire town has been affected. Helping people to overcome trauma is a major issue and teams of Japanese Red Cross Society counselors are being deployed to combat stress-related illnesses that are beginning to emerge.

Certainly, life in the evacuation centers isn’t easy for the young either. Ayumi Yamazaki, 21, sits in the large gymnasium with her older sister, niece, mother and one-and-a-half year-old daughter, Yuwa. Her house was destroyed in the tsunami. She just managed to escape, first to a nearby hill, but when the churning mass of debris brought in by the tsunami caught fire, she was forced further up the mountain.

“We get one bowl of soup or one piece of bread to share among three people,” she said. “It’s cold here, and these two (pointing to her daughter and niece) caught a cold but just now we got some medicine from the Red Cross.”

At the Otsuchi municipal council, Koso Hirano, has a massive job on his hands. By default, he assumed control of the council when the Mayor and seven other council members died when the tsunami came in.

“We always thought we were well prepared,” he said. “We built six meter (20 feet) barrages and dykes but the wave was ten meters (33 feet) high and people barely had twenty minutes to escape”, said Hirano whose main task now is ensuring that evacuees have sufficient food and water supplies.

 

https://american.redcross.org/site/Donation2?idb=0&5052.donation=form1&df_id=5052

 

 

Red Cross Response

The American Red Cross announced an initial contribution of $10 million to the Japanese Red Cross Society Tuesday to assist in its ongoing efforts to provide medical care and relief assistance to the people of Japan following the March 11 earthquake and tsunami.

In addition to financial assistance, a disaster management expert from the American Red Cross traveled to Japan last week for a short mission to provide support and advice to the Japanese Red Cross Society, which continues to support the Japanese government’s earthquake and tsunami response.

 

People at the high school evacuation centre in Ostuchi.

Photo: Patrick Fuller/IFRC

 

Otsutshi, one elderly couple huddled around a wood stove in the corner of the vast gymnasium simply stare blankly into the flames.

Photo: IFRC

Reaching Vulnerable Survivors by Bicycle

In face of a fuel shortage which is hampering relief supply deliveries and the mobility of medical teams, the Japanese Red Cross Society has been finding alternative ways to ensure aid reaches the most vulnerable survivors.

“If there’s no petrol, I can’t get around, but I know there are old people on their own, so I am visiting them by bicycle to make sure they are OK,” said Shinya Hirakuri, a disaster management team leader.

Following days of near constant response, a number of Japanese Red Cross teams are rotating out for rest periods. On their return to Tokyo from the most affected areas in the northeast through unseasonal snow falls, they have reported that compared to the immediate aftermath of the disaster, traffic and relief activity is steadily becoming more intensive.

Although traffic is improving, it will likely remain a challenge for some time yet. As an example, to get to devastated communities in Miyagi prefecture, north of Fukushima where the damaged nuclear plant lies, requires a long detour via Niigata, further west, adding dramatically to travel times. This coupled with fuel shortages causes delays the arrival of supplies and relief workers and keeps survivors isolated.

Working hard to keep the world’s focus on the humanitarian situation despite the unfolding nuclear crisis, the Japanese Red Cross Society is forming additional plans for continuing its support to affected populations in case the exclusion zone around the trouble reactors widens.

A seven-person international advisory team, which includes an American Red Cross representative, will work throughout the weekend and beyond with the Japanese Red Cross Society to move relief and recovery operations forward as well as defining ways for the global Red Cross Red Crescent network to provide support.

About the American Red Cross:
The American Red Cross shelters, feeds and provides emotional support to victims of disasters; supplies nearly half of the nation’s blood; teaches lifesaving skills; provides international humanitarian aid; and supports military members and their families. The Red Cross is a charitable organization — not a government agency — and depends on volunteers and the generosity of the American public to perform its mission. For more information, please visit www.redcross.org or join our blog at http://blog.redcross.org.