Response: further reflections on Virchow's Triad.

To the Editor: I am pleased that our piece about Virchow and his eponymous triad generated such a detailed and thoughtful response. Dr. Malone agrees with our main point: Virchow did not identify stasis, hypercoagulability, and vessel wall injury as the three main precipitants of thrombosis. However, Dr. Malone is concerned that we refer to the original triad (the consequences of thrombosis) and the modern triad (the causes of thrombosis) as "one in the same." We agree wholeheartedly that these are not (literally) the same. Our intent was to illustrate that the precipitants of thrombosis and the consequences of thrombosis are mechanistically inseparable, not to imply that Virchow, in 1856, had truly defined or anticipated the modern triad.

Although we did not provide a detailed discussion of Virchow's interpretation of "stasis" and "hypercoagulability" in our original piece, it is clear that Virchow did recognize stasis (a marked slowing down of blood flow) as an important precipitant of thrombosis: "The formation of these extended clots [into the inferior vena cava] can also be explained by another cause. If the blood of a major vessel clots, for instance [the common iliac vein] ... an entire extremity is cut out of the circulation, then only the blood of one iliac vein will supply the inferior vena cava. And especially in that part of the cava which is next to the obturated iliac, a layer of almost stagnating blood will develop. This situation is by all means able to initiate coagulation of the blood." (1)

Similarly, Virchow comments on the importance of stasis in precipitating pelvic vein clots in a patient with typhoid fever: "This case was even more predisposed because of the special anomaly in the course of the veins. If there is a general or localized reduction in blood flow, we usually see spontaneous coagulation, most frequently in those veins that have anastomoses or that form a plexus, which means that they have a certain number of superfluous ducts ..." (1)

Virchow's perception of coagulability (and hypercoagulability) was far less refined, but he did allude to the concentration of fibrin in the blood as a potential determinant of coagulability, and he recognized that the blood's "adhesiveness" could be increased by adding oil, paste, and other substances to the blood. (1)

As pointed out in our original piece, Virchow downplayed the role of the endothelium in precipitating thrombosis, probably as a way to convince his contemporaries that pulmonary thrombi originated in the deep venous system and did not form in situ (in response to inflammation of the pulmonary arteries). (2)

Regardless of these subtle differences in opinion, we appreciate Dr. Malone's letter in that it emphasizes the complex evolution of our modern conceptualization of venous thromboembolism. Indeed, there are many indications that Virchow could not have truly anticipated the modern triad based on prevailing 19th century thinking and his own views of thrombosis. A question that (at least for me) remains to be answered is this: Who coined the term "Virchow's Triad" and what was the original intent of the term? I have been unable to find historical texts that provide an answer to this simple question. The two citations that Dr. Malone provides do discuss the concepts of hypercoagulability, vessel wall injury, and stasis, but only credit Virchow (correctly) for recognizing the importance of stasis. (3,4) Perhaps Dr. Malone or one of the Journal's readers can provide an answer.

References

1. Virchow R. Gesammelte Abhandlungen zur Wissenschaftlichen Medicin. [Thrombosis and Emboli, Translated by AC Matzdorff and WR Bell. 1998]. Canton, MA, Science History Publications/USA, 1856.

2. Brotman DJ, Deitcher SR, Lip GY, Matzdorff AC. Virchow's triad revisited. South Med J 2004;97:213-214.

3. Wessler S. Thrombosis in the presence of vascular stasis. Am J Med 1962;33:648-665.

4. Mustard JF, Murphy EA, Roswell HC, Downie HG. Factors influencing thrombus formation in vivo. Am J Med 1962;33:621-647.

Daniel J. Brotman, MD

Hospital Medicine Fellowship

General Internal Medicine/S70

Cleveland Clinic Foundation

Cleveland, OH