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Let’s take it from the D-dimer
Great medical progress has been seen in the treatment of deep vein thrombosis in one generation.
Wow, what a weekend! In March 2008, I played piano with the Cleveland Pops Orchestra in its hometown for a concert with Bernadette Peters on a Friday night and Steve Lippia, who sang the Sinatra Song Book, on a Saturday night. What a thrill it was to play for both Bernadette and Steve!
On further reflection, I realized that the masterful playing of several orchestra members that weekend could be attributed indirectly to advancements in medicine. One of the Cleveland Pops’ great musicians, not quite 50 years old, was likely cured of his prostate cancer with surgery in January of this year. His rapid recovery allowed him to play with us that night. One of the violinists must have known I was a physician, because she confided in me that she was just back to playing, having had wrist surgery recently on her left hand. She beautifully played several solo passages in Bernadette’s show. I was able to play after hernia surgery, which relieved my constant groin pain and removed the threat of incarceration.
 Arthur Topilow |
The most prominent member of the orchestra, my brother Maestro Carl Topilow (see www.carltopilow.com), had a kidney obstruction last June that required a double J catheter insertion and not surgery. Three days after he received anesthesia for this problem, he flew to Colorado to conduct his summer graduate student orchestra. He called me in the morning two days later, while I was in the hospital:
“My foot is swollen.”
“What do mean, your foot is swollen?”
“It’s swollen.”
“When you push on your foot, does it pit?”
“Yes.”
“Go to the hospital”
“No, I have to conduct a rehearsal.”
“Forget it.”
“Really?”
“Yes, really.”
“Can’t I go later?”
“No!”
Carl went to the Summit Medical Center in Dillon, Colo., where he had his sonogram, and was prescribed Lovenox (enoxaparin sodium injection, Sanofi-Aventis), warfarin and an elastic stocking for his deep vein thrombosis. He was back on the podium two days later.
Together with our families we flew to Italy later last summer to perform some duo concerts — Carl plays the clarinet, as well as conducts.
Carl, who is fluent in Italian, chatted with the staff while a nun took his blood for a prothrombin time/international normalized ratio in Arezzo in Tuscany, giving us a result in 20 minutes. It showed that he was in the therapeutic range. He took six months of warfarin and had a normal D-dimer one month after stopping the drug. Sixty-five years ago my mother-in-law was prescribed complete bed rest for three months after her pregnancy-related DVT. What a contrast! Carl had out-patient injectable and oral anticoagulation.
While in Italy he had a reliable blood test because of the international standards set up by the World Health Organization and the International Committee on Thrombosis and Hemostasis. He was able to stop anticoagulation, with some confidence, after a normal D-dimer report.
A recent article by Palareti described the usefulness of the test after warfarin therapy cessation. In his study, “patients with an abnormal D-dimer test who resumed anticoagulation had a significantly lower combined incidence of recurrent venous thromboembolism and bleeding than did those who did not resume anticoagulation. Patients with a normal D-dimer level did not resume anticoagulation. The optimal course of therapy for such patients is not clearly established.” Implied, but not a primary end point of the study, is that it is safe to stop anticoagulation in a patient with no other risk factors who has a normal D-dimer level after the cessation of anticoagulation. My brother has not had a recurrence and is actively conducting and playing clarinet four months after stopping warfarin. Because of his rapid sonographic diagnosis and subsequent treatment, he has not had any signs of a post-phlebitis syndrome. He continues to use his elastic stocking.
A little history
In the early 1940s when my mother-in-law had her phlebitis, there was no heparin, warfarin or sonography. Dr. George Ludwig first investigated ultrasound for medical purposes in the late 1940s at the U.S. Naval Research Institute. In 1955, Drs. John Julian Wild and John Reid presented one of the first papers on ultrasound used for medical diagnostics, entitled “Echographic Tissue Diagnosis.” I remember as a student in the late 1960s holding the ultrasound probe over a patient’s temple to see if there might be a midline shift of the brain. Only in the last 15 years or so has sonography been widely used as an accurate method of diagnosing DVT.
Warfarin was first used in the 1950s as an anticoagulant for myocardial infarction and strokes. It gained fame when used to treat President Eisenhower after his 1956 coronary event while in office. Heparin was discovered in 1916 at Johns Hopkins University, but was not practically applied by doctors until the early 1930s when a research team that included Dr. Charles Best (of insulin fame) developed a method to make available a purified, plentiful and inexpensive supply that was safe for human use. Its application in a limited number of patients began in the 1940s. Lovenox was initially approved for use in thrombosis in 1993. The D-dimer, a fibrin degradation product present in blood after a clot is degraded by fibrinolysis, was introduced in the 1990s as an aid in excluding the presence of DVT and low probability pulmonary embolism.
Several days after my brother’s recovery from his DVT, I flew to Colorado. I listened and watched him conduct the National Repertory Orchestra in Breckenridge. I couldn’t help feel pride that modern medicine’s miracles kept him on the podium, thanks to dedicated scientists and researchers through the past 100 years or more.
Arthur Topilow, MD, is in private practice at Atlantic Hematology & Oncology in Manasquan, N.J.
N Engl J Med. 2006;355:1780-1789.