Further reflections on Virchow's triad.

To the Editor: Brotman et al (1) discussed the relation between the original, classical, and "modern" versions of Virchow's triad. The 1856 original summarized the effects of thrombosis, not its cause, and they recognize that the "modern" triad is "not what Virchow originally described," but they conclude "After 150 years, it turns out that Virchow's original triad and its modern interpretation may be one and the same." I would dissent from this conclusion in significant respects.

Shortly after 1962, Virchow's classical triad, having survived for 100 years, was replaced by "Stasis, hypercoagulability, and vessel wall injury"--the "modern" version. But "stasis" is not synonymous with "interruption of the blood stream"; nor is "hypercoagulability" synonymous with "phenomena due to blood coagulation." "Vessel wall injury" is the sole relic of Virchow's original and classic versions. Brotman et al's apparent wish to corral "Virchow's triad" in the thesis that "endothelial damage, hypercoagulability, and stasis lead to thrombosis" reveals their own paradigm.

They quoted (2) Virchow's purported opinion about "stasis"--but that quotation continued: "The doctrine of stasis rests on manifold misinterpretations--(etc)." Stasis had been Boerhaave's research paradigm in the early 18th century until debunked by Hewson's experiment in 1772, which proved that blood "at rest" (no longer circulating) does not clot normally. Hunter substituted an "endothelial injury" paradigm, and Virchow, a committed Hunterian, deliberately OMITTED (the word) "stasis" from "Phenomena due to the interruption of the blood-stream." (Our blood-stream is always "interrupted" [driven by intermittent cardiac and other muscular contractions], sometimes more than others.)

Wessler's and Mustard's papers (2-4) reintroduced the Boerhaavian paradigm by stripping "interrupted-moving (blood)" from Virchow's (Harveian/Hunterian) triad. It was reduced to a dyad of hypercoagulability and vessel wall injury after 1962.

Hypercoagulability was not mentioned in Virchow's time, or before 1947, and it could still be a shibboleth today. Perhaps a hypothetical spectrum ranging from the "incoagulability" of hemophilic blood to the "hypercoagulability" of blood in which "thrombi" have formed was presumed after Owren's work in 1947 et seq. It is debatable whether any phenomenon of "hypercoagulability" has truly been characterized, but we need not debate this here. What matters is that it was not part of either Virchow's triad between 1856 and 1947. His "phenomena due to blood coagulation" referred to normal clotting. "Hyper" coagulation was superfluous, since even normal blood clotting--once initiated--would form casts of the blood vessels and instantly stop the circulation. It was reasonable after 1947 to posit a "hypercoagulable state" and then seek evidence for it, but the success of anticoagulation therapy does not constitute such evidence. Physicians and surgeons do not routinely establish that their patients suffer from "hypercoagulability" before they administer anticoagulants. Philosophically, they are unconcerned whether they are scaling hypercoagulability down to normal coagulability or normal coagulability down to hypocoagulability. Virchow's triad does not impinge on the therapeutic value of monitored anticoagulation, and anticoagulation is irrelevant to whether the modern version, the classical version compiled by Virchow's successors, and the original triad are "one and the same."

It may be less contradictory to conclude that thrombosis follows a troika of (1) circulation (invariably interrupted), which must cause (2) vascular endothelial death if it fails for long, and may thus entrain (3) the coagulative property of normal blood to obstruct vessel tract(s) thus rendered prenecrotic or worse.

References

1. Brotman DJ, Deitcher SJ, Lip GYH, et al. Virchow's triad revisited. South Med J 2004;97:213-214.

2. Virchow R. Cellular Pathology. [F Chance transl.] 2nd edition. Philadelphia, JB Lippincott, 1863.

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

4. Mustard JF, Murphy EA, Rowsell HC, et al. Factors influencing thrombus formation in vivo. Am J Med 1962;33:621.

P. Colm Malone, MD, FRCS 

Birmingham, United Kingdom