title: Deep venous thrombosis: The valve cusp hypoxia thesis and its incompatibility with modern orthodoxy.
abstract: The valve cusp hypoxia thesis (VCHT) of the aetiology of deep venous thrombosis (DVT) was adumbrated in this journal in 1977 and fully articulated in 2008, the original hypothesis having been strongly corroborated by experiments published in 1981 and 1984. It presents a unitary account of the pathogenesis of venous thrombosis and embolism that is rooted in the pathophysiological tradition of Hunter, Virchow, Lister, Welch and Aschoff, a tradition traceable back to Harvey. In this paper we summarise the thesis in its mature form, consider its compatibility with recent advances in the DVT field, and ask why it has not yet been assimilated into the mainstream literature, which during the past half century has been dominated by a haematology-orientated 'consensus model'. We identify and discuss seven ways in which the VCHT is incompatible with these mainstream beliefs about the aetiology of venous thrombosis, drawing attention to: (1) the spurious nature of 'Virchow's triad'; (2) the crucial differences between 'venous thrombus' and 'clot'; the facts that (3) venous thrombi form in the valve pockets (VVPs), (4) DVT is not a primarily haematological condition, (5) the so-called 'thrombophilias' are not thrombogenic per se; (6) the conflict between the single unitary aetiology of DVT and the tacit assumption that the condition is 'multicausal'; (7) the inability of anticoagulants to prevent the initiation of venous thrombogenesis, though they do prevent the growth of thrombi to clinically significant size. In discussing point (7), we show that the VCHT indicates new approaches to mechanical prophylaxis against DVT. These approaches are then formulated as experimentally testable hypotheses, and we suggest methods for testing them preclinically using animal trials.
authors.affiliation: Theoretical Medicine and Biology Group, 26 Castle Hill, Glossop, Derbyshire SK13 7RR, UK.
authors.forename: P Colm
authors.initials: PC
authors.lastname: Malone
authors.affiliation: Theoretical Medicine and Biology Group, 26 Castle Hill, Glossop, Derbyshire SK13 7RR, UK. Electronic address: tmedbiol@gmail.com.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Agutter
mesh_terms: D000818:Animals; D001777:Blood Coagulation; D001783:Blood Flow Velocity; D006801:Humans; D008955:Models, Cardiovascular; D011673:Pulsatile Flow; D020246:Venous Thrombosis / Q000209:etiology / Q000503:physiopathology*; D055422:Venous Valves / Q000503:physiopathology*