Andrew J. Hughes, Emanuele Chisari, Javad Parvizi., Geoffrey Westrich, David Beverland.
Response/Recommendation: Deep venous thrombosis (DVT) propagation, causing pulmonary embolus (PE), has been described in patients with unprovoked clots and attributed to the prothrombotic phenotype of the individual. While it is recognized that a PE may arise from a DVT, a direct relationship between DVT propagation and a PE does not appear to exist for orthopaedic surgery patients that undergo total joint arthroplasty (TJA).
Strength of Recommendation: Moderate.
Rationale: Understanding the natural history, prognosis, and implications of venous thromboembolism (VTE) occurring as a consequence of orthopaedic procedures is imperative. Despite DVT rates falling to as low as 0.4% post total hip arthroplasty (THA), and 0.8% post total knee arthroplasty (TKA), consensus is lacking regarding the risk of propagation of distal DVT to the lungs1-4. Much of the literature pertaining to the natural history of VTE reports on unprovoked DVT or those provoked in the setting of prothrombotic risk factors, the pathophysiology of which differ from the provoked postoperative DVT5-7. A causal relationship between DVT and PE has not been proven in patients undergoing lower limb TJA)1,8,9.
Surgery has been reported as a major, but transient, trigger for VTE10-12. Local activation of the clotting cascade begins intraoperatively following endothelial injury and the release of tissue thromboplastin, which promotes an inflammatory feedback loop involving procoagulant proteins and fibrin strands13,14. This transient prothrombotic environment, encompassing distal venous valve pockets that provide a nidus for clot formation, predispose orthopaedic patients to a higher rate of ipsilateral DVT than those undergoing major non-orthopaedic procedures7,13,15. Amongst surgical specialties, however, retrospective research has shown that PE rates in the arthroplasty cohort are no higher than those undergoing gastrointestinal, vascular, or gynecological procedures16. If a DVT was to consistently propagate to cause a PE post arthroplasty, the literature would appreciate a significantly elevated PE incidence compared to other surgical specialties, in proportion to that of DVT rates, however, this is not the case.
PE are thought to most commonly arise by way of an established distal thrombus becoming dislodged, travelling within the returning circulatory system to the lungs, obstructing arterioles within the pulmonary vasculature, and causing ischemia5. Thrombosis can also arise directly within the pulmonary vasculature. Patients at risk of in-situ pulmonary artery thrombosis display a pronounced prothrombotic phenotype, with contributions from abnormal fibrinogen variants, family history, autoimmune disease, endocrine dysregulation, and active cancer5,17,18. Separate to both hematological pathophysiological pathways, increased intramedullary pressure during arthroplasty procedures has been shown to embolize prothrombotic fat, bone marrow, and cement fragments through systemic veins into the pulmonary vascular system13,19,20. Activation of extremity and pulmonary thrombogenesis, by way of thromboplastin exposure, has been hypothesized to contribute to DVT and PE rates following TJA, however, intraoperative steps have been taken to mitigate this process13,20. Manifestation of symptomatic PE is a complex, multifactorial process, with multiple pathophysiological pathways likely coexisting in genetically susceptible patients, however propagation of an extremity thrombus does not appear to consistently contribute to the burden of arthroplasty-related PE disease21-23.
Little exists in the literature to clarify the evolution of incidental asymptomatic DVT, as evidenced by the lack of consensus within published guidelines7,24-26. Observational studies have confirmed that the majority of isolated deep DVT display an uneventful clinical course, without embolization27. Half of such thrombi arise at the time of surgery and resolve spontaneously within the first 72 hours postoperatively27. Whereas unprovoked, proximal DVT are concerning given their tendency to propagate to cause a PE, and risk of recurrence27-32. In the provoked postoperative setting, however, PE rates do not appear to correlate with the observed incidence of proximal DVT, which have been identified in 27% of all DVT post-THA, and 15% of all DVT post TKA33,34. An increased proximal DVT rate in those undergoing THA has not translated into a heightened burden of PE compared to those post TKA22,35.
Perioperative prophylaxis and early mobilization have made significant progress in the fight against VTE, which can be appreciated via the falling incidence of post-arthroplasty DVT6,36,37. In contrast, due to radiological advancements, and the ability to now discern even smaller emboli, the incidence of PE has been seen to increase the last two decades38,39. Highly sensitive multi-detector row computer tomography (CT) pulmonary angiography scanning allows for the detection of clinically insignificant disease in the postoperative setting, arising within the periphery of the pulmonary vasculature39-41. Despite prophylaxis and enhanced recovery pathways, the rate of clinically significant PE persists between 0.2 – 1.1% of all arthroplasty patients22,42-44. The proportion of TJA patients at risk of PE development has remained consistent over the past two decades, regardless of compliance with guidelines directed towards reducing the venographic evidence of DVT7,44.
Whilst unprovoked lower extremity DVT carries a risk of propagation, this has not been proven to occur in the provoked perioperative orthopaedic setting1,4. PE are thought to arise via multiple interacting pathophysiological processes, most likely within genetically susceptible patients undergoing TJA. Robust scientific evidence, investigating the propagation tendencies of the provoked postoperative DVT, is lacking. Carefully designed, prospective research will play a vital role in clarifying our understanding of perioperative VTE as a disease, most notably its natural history and prognosis in the arthroplasty patient.
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