Trousseau, thrombosis and cancer: A history consult

Physicians and students can learn by contemplating how history intersects with their daily practice.

A history consult can be a useful tool for modern health care professionals. For example, nearly all medical students will be involved in caring for patients with cancer. In patients with a malignancy, venous thromboembolism is a common, potentially fatal, and preventable condition. Dr. Armand Trousseau (1801-1867), a perceptive French internist, recognized the connection between malignancy and thrombosis over 100 years before effective treatment was available.

Dr. Trousseau's understanding of the human body evolved from the work of many prominent physician scholars before him. The first known description of thrombophlebitis (vein inflammation from a thrombus) dates back to the 13th century A.D. An account of unilateral edema and sepsis was included in “Les miracles de Saint Louis” by Guillaume de Saint-Pathus. In this account, a French man named Guillot “was overtaken in the ankle of his foot on the right side by a swelling of the part which became abscessed and gave him pain…and this said illness rose from the foot up the leg, from the leg to the thigh, and became envenomed and engorged.” Physicians were unable to help him, advising him to seek divine intervention. He was miraculously cured in 1271 A.D. by the relics of St. Louis.

Courtesy of Maureen Murphy-Ryan
Courtesy of Maureen Murphy-Ryan.

Over subsequent centuries, thrombophlebitis became recognized as a medical phenomenon, and later physicians began investigating its causes. Phlegmasia dolens (“painful edema,” an early term for deep vein thrombosis) has been recognized as a distinct clinical entity since at least 1593 when German surgeon Guilelmus Fabricius Hildanus (also known as Wilhelm Fabry, 1560-1634) described it in his first book, a treatise on gangrene. Phlegmasia alba dolens or “painful white edema” refers to the milder of the two categories into which deep vein thrombosis has historically been divided. The more severe and uncommon ischemic cyanotic variety was known as phlegmasia cerulea dolens (“painful blue edema”).

Dr. Armand Trousseau was the first to describe the connection between cancer and increased risk of thrombosis with one of his two eponymous clinical signs, the Trousseau sign of malignancy, also referred to as Trousseau syndrome. It refers to the spontaneous, recurrent formation of clots in different places (migratory thrombophlebitis) in patients with malignancies. In his 95th lecture in a series on clinical medicine (delivered at the Hôtel Dieu in Paris, where he was physician-in-chief), Dr. Trousseau noted:

“I have long been struck with the frequency with which cancerous patients are affected with painful edema in the superior or inferior extremities, whether or not either was the seat of cancer. This frequent concurrence of phlegmasia alba dolens with an appreciable cancerous tumor led me to the inquiry of whether a relationship of cause and effect did not exist between the two, and whether the phlegmasia was not the consequence of the cancerous cachexia.”

Dr. Trousseau presciently attributed thromboembolism in malignancy to changes in blood composition rather than local inflammatory or mechanical forces. By correlating clinical observation with surgical and autopsy findings, Dr. Trousseau recognized that a localized cancer could induce a generalized hypercoagulable state in which thrombosis could occur elsewhere in the body, such as in extremities with visceral malignancy. Dr. Trousseau described several cases in which recurrent thrombosis was the presenting feature of visceral cancer, and his confidence in the utility of this connection led him to say, “So great, in my opinion, is the semiotic value of phlegmasia in the cancerous cachexia, that I regard this phlegmasia as a sign of the cancerous diathesis as certain as sanguinolent effusion into the serous cavities.”

The discovery later allowed Dr. Trousseau to diagnose himself. At the age of 66, he noticed phlebitis in his left upper arm. He diagnosed a visceral malignancy, and died of gastric cancer only months later. Ultimately, the actual prognostic value of idiopathic deep vein thrombosis for occult cancer was found to be less than he had anticipated. However, thrombosis remains a critical clinical feature to recognize in the setting of malignancy, given its prevalence, the severity of potential complications, and its current treatability. Clinicians and researchers are still building on this historical foundation by investigating hypercoagulability in malignancy and modifying best thrombosis management practices based on new data. The precise nature of the association remains unknown, but a spectrum of molecular causes is suspected.

Even in today's world of rapid advances in medical technology and pharmacology, physicians—and medical students—can find contextual meaning and practical benefit in contemplating the intersection of history with their daily practice.