Saving life and limb
Doctors give life back to woman with nearly fatal blood clot
This article from the National Institute of Health Web Site, December 2002
http://www.cc.nih.gov/ccc/ccnews/dec02/ Three months ago Rebecca McDonald gave birth to her third child, Jordan. A couple of weeks later, a blood clot had formed in her pelvic area and stretched its way down to her calf. The swelling from her leg became crippling. Her life began to revolve around a wheelchair, her bed and doses of morphine for the pain.
"The scary part was not knowing what the future was going to be," said Rebecca, a stay-at-home-mother of three from Boise, Id. "How was I going to parent my children from a bed?"
And how was her husband Robert going to care for her, a newborn, two daughters, ages five and seven, and still hold down his job as a dentist?
Pictured are (l to r): Denise McLaughlin, R.N., 7E charge nurse; Rebecca McDonald; 3-month-old Jordan; Robert McDonald; Dr. McDonald Horne and Dr. Richard Chang.
They were unsure; but, more than 2,300 miles away, Clinical Center Doctors Richard Chang and McDonald Horne were searching for patients like Rebecca.
"She's very healthy and runs every day," said Robert McDonald. "She was running before she became pregnant and started running again after the baby was born."
It was then that she began to have pain in her left calf area. "We thought that maybe she just stretched the muscle. She took Ibuprofen, but it got worse," said Robert. "So we went on a Saturday to a clinic just to get it checked out."
The clinic sent them to the emergency room at St. Luke's Hospital in Boise. "After they ran some tests, the nurse came in with tears in her eyes and said she was happy that we came in when we did because she had a pulmonary embolism and it was life threatening."
A pulmonary embolism is a blocked artery in the lungs that is generally caused when a blood clot or a portion of a clot from another part of the body travels to the lungs.
Rebecca was placed on anticoagulants, medications used to dissolve and prevent blood clots. After a week in the hospital she was sent home. "The treatment wasn't working. Her leg was getting bigger and becoming worse. It was twice the size of her other leg." said Robert. "I rented a hospital bed because she couldn't go up and down the stairs. The pain pills were like TicTacs. . . they just weren't working . . . so we went back to the emergency room and they put her on morphine."
As a dentist, Robert said he was familiar with clinical trials. So he went to his computer and began looking for websites that could give him information about clinical trials for severe blood clots.
"NIH was the first website I found. I called them the next day at six o'clock in the morning and they said Rebecca would be the perfect candidate," said Robert. "We took a flight out that same night."
According to Dr. Chang, chief, Special Procedures Section, Department of Radiology, Imaging Sciences Program, nearly 200,000 people suffer annually from deep venous thrombosis or DVT, a blood clot in the lower part of the body.
"Most of these cases will be treated with anticoagulation drugs alone. This would be great if anticoagulation was perfectly effective," said Dr. Chang. "Anticoagulation is extremely effective in the prevention of pulmonary embolisms, and it is also fairly good at preventing DVT in the first place. Where it fails, is in clearing the clot in the leg and preserving the function of the veins in the legs."
In Rebecca's case, anticoagulation wasn't working. As her uterus expanded during the pregnancy, it pressed against the veins in her pelvic area, narrowing the vein channel. This reduced blood flow and allowed the blood to clot.
According to Dr. Horne, senior clinical investigator, Hematology Services, Department of Laboratory Medicine, even if the anticoagulants worked in clearing the blockage, the vein would still be narrow, increasing the chance of developing another blood clot.
Anticoagulants will dissolve a clot within several weeks or several months. However, it leaves behind damage to the vein. Within each vein are delicate valves that allows blood to flow up the leg. Without the valves, or with damaged valves, pressure builds up in the veins, leading to swelling, and potentially reclotting, and possibly skin ulcers.
"But if we move the clot out quickly, the venous valves remain functional," said Dr. Horne.
And that was the theory behind their research. In 1998, Dr. Chang and Dr. Horne began recruiting patients for a clinical trial for treatment of acute deep vein thrombosis.
For almost 15 years, Dr. Chang treated cancer patients who developed blood clots in the neck and arms caused by catheters used during chemotherapy. "We studied and tried different ways of dissolving the clots, but we weren't quite happy with the results from techniques used in the general medical community," said Dr. Chang.
By 1994, Dr. Chang and Dr. Horne decided to test rtPA, a natural protein that was generally used for patients who have had heart attacks. By using a catheter to spray the enzyme directly into the clot, the doctors hoped to dissolve the clot within days, if not hours after treatment. Unlike the other alternative choices of clot dissolving enzymes, rtPA sticks directly to the clot, allowing prolonged enzymatic action, dissolving the clot to restore a channel for blood to flow again. Anticoagulants themselves do not dissolve clots and when patients are placed on anticoagulant therapy alone, their physicians are relying on natural clot-dissolving enzymes to penetrate the clot and dissolve the clot. This is a very slow process when the clot is large and blocks flow of enzyme reaching the area.
"Ideally, patients should get rtPA treatment within two weeks of diagnosis. Referring doctors should not delay if the patient has extensive DVT," said Dr. Chang. "Thrombolytic therapy is very effective when the clot is fresh. Doctors and their patients should not adopt a wait-a-month-and-see approach, because they will miss the period when thrombolytic therapy is most effective."
However, many doctors have been reluctant to support what Dr. Chang and Dr. Horne have found to be successful among patients they have treated with DVT.
"We received limited patient referrals from other physicians," said Dr. Chang. "They said it wasn't proven, it doesn't work, it's too dangerous; all information from older studies over 10 years ago. I think this is no longer true and thrombolytic therapy deserves a fresh reevaluation."
And the results are starting to prove him right.
Of the 14 people who have participated in the study, all have had successful results—including Rebecca. Within three days Rebecca was walking. Within a week, she was back to running two miles a day.
"It's not a coincidence that this clotting occurred after Rebecca's pregnancy. We were surprised that it didn't happen during the pregnancy," said Dr. Horne. "However this case was unique because of the severity of it. This is a young, active individual who had pain and swelling in her leg that was not improving with anticoagulants. Eventually, she would have been severely debilitated and crippled."
Blood clots can develop from pregnancy, birth control pills, hormone replacement, cancer, and several other rare situations, according to Dr. Chang. "Many people who are athletic or have an active lifestyle are at a higher risk, especially if they become sedentary or confined to a chair or a bed for a period of time," he said.
That's exactly what happened to Dr. Ryszard Pluta, clinical staff physician, Surgical Neurology, NINDS. After returning from a 17-hour flight from China, Dr. Pluta felt a pain in his right calf. He decided to have an ultrasound and found that he was suffering from economy class syndrome.
This condition results from long hours of minimal movement on an airplane when passengers are crammed into small quarters.
"Nearly ten percent of travelers develop DVT, but less than one percent are actually diagnosed," said Pluta. "Many fly in business class or first class, but the same percentage get DVT."
Pluta was accepted into the clinical study and within a week returned to his regular activities of running, tennis, swimming, and golfing.
"This is a blessing," said Pluta, who now flies more European airlines that remind passengers to stretch and move around every hour to avoid the risk of blood clotting. "The fact that this is giving people a real chance to go back to their normal life is great."
– by Tanya Brown, NIH
This article from the National Institute of Health Web Site, December 2002