P. Colm Malone and Paul S. Agutter have written a remarkable book about deep venous thrombosis (DVT) called “The Aetiology of Deep Venous Thrombosis: A Critical, Historical and Epistemological Survey” (2008). The book is remarkable for the following three reasons. The authors discuss the aetiology of DVT in a historical, philosophical and epistemological context. Secondly, they propose an ‘pathophysiological’ alternative to the “consensus model” of DVT. Finally, they devote a complete chapter to a topic that should be of great interest to researchers and practitioners of critical care medicine and human cryopreservation; post-mortem blood coagulation.
In the first chapter, the authors introduce the phenomenon of DVT, its pathological consequences, and characterize what they call the ‘consensus model’ of DVT. This consensus model, which is often taught as ‘Virchow’s Triad’ (named after Rudolf Ludwig Karl Virchow), teaches that DVT is caused by a) ‘hypercoagulability’, b) ‘stasis’ of venous blood, and c) injury to vein wall intima (endothelium). In the following chapters the authors argue that this consensus model is wrongly attributed to Virchow, debunk hypercoagulability and stasis as causes (instead of predisposing factors) of DVT, and reinterpret the third cause as injury to the venous valve cusp.
In short, the aetiology of DVT the authors propose is that under non-pulsatile flow conditions interruption of the valve cycle will cause blood to be sequestered in the valve sinus, resulting in local hypoxaemia. Sustained non-pulsatile flow will cause formation of a thrombus on the oxygen-starved parietalis endothelium of the valve cusp leaflets.
In a long, but fascinating historical exegesis, the authors contrast the “pathophysiological” with the “mechanistic” approach to biomedical research, and argue that the dominance of the latter approach led to our current flawed understanding of the aetiology of DVT. One does not have to follow the authors in attributing the current consensus on DVT to the dominance of certain philosophical approaches to biology to appreciate the logical arguments and empirical evidence that is presented to support their view of DVT. As can be expected from a long treatise on DVT, the authors also throw light on such phenomena as traveler’s thrombosis, anesthesia-induced DVT, and even the pathophysiology of crucifixion.
Of most interest to critical care medicine and cryonics is the treatment of blood coagulation in relationship to “stasis.” Throughout the text, the authors review the argument that in vivo blood stasis as such induces coagulation and find it lacking. This discussion culminates in chapter 13 called “Cadaver Clots or Agonal Thrombi?” where they conclude that blood cannot coagulate in a cadaver and that all thrombi (which the authors carefully distinguish from in vitro clots) are agonal in nature. The “mode of death” framework they present allows the authors to explain why thrombi are found in some cadavers but not in others.
If the authors are right, the consequences for resuscitation protocols and cryonics should be evident. Whether anticoagulant and thrombolytic therapy during stabilization will be beneficial depends on the pathophysiology of the patient prior to death. In the case of sudden circulatory arrest we would not expect much benefit from “post-mortem” anti-thrombotic therapy, whereas in the case of gradual and selective circulatory failure (shock) we would expect increased thrombi formation.
One important caveat for trauma and cryonics patients is that some stabilization procedures themselves may produce thrombi as a result of alternating cycles of hypoxia and non-pulsatile flow. It should also be kept in mind that circulatory arrest induced blood abnormalities are not confined to blood coagulation. For example, the case for rapid post-arrest hemodilution and hypertension to counter blood sludging caused by aggregation of red blood cells remains strong. And in light of practical limitations to determine the presence and magnitude of thrombi in cryonics patients, combinational pharmacotherapy to secure fluidity of the blood remains warranted for most, if not all, cryonics patients.