On “Role of Physical Therapists in the Management of Individuals at Risk for or Diagnosed With Venous Thromboembolism: Evidence-Based Clinical Practice Guideline 2022.” Hillegass E, Lukaszewicz K, Puthoff M. Phys Ther. 2022;102:pzac057. https://doi.org/10.1093/ptj/pzac057

We read with great interest the new edition of the “Role of Physical Therapists in the Management of Individuals at Risk for or Diagnosed With Venous Thromboembolism: Evidence-Based Clinical Practice Guideline.”1 We applaud the commitment of Hillegass et al to advance the practice of physical therapists in the realm of mobility and venous thromboembolism (VTE). The overarching theme of the guideline was to encourage the mobilization of patients with VTE. However, when discussing the timing of initiation, the authors recommended withholding mobilization until patients achieved a therapeutic level of anticoagulation.1(pp15,16,18-20,24,25,30) In particular, Action Statement 10 stated that “when a patient with a recently diagnosed lower extremity deep vein thrombosis (DVT) reaches the therapeutic threshold of anticoagulant medication, physical therapists should mobilize the patient.” We worry that this recommendation may result in unnecessary immobility, especially among patients who require unfractionated heparin. It appears that the authors’ recommendation to delay mobility is based on the idea that “low molecular weight heparin, through the drug’s anti-inflammatory properties, make a clot less likely to migrate as an embolus.”1 Indeed, scientists have observed the anti-inflammatory effects of heparin and its derivatives, but the reduction in clot migration has not been well-described in the literature, including in the references cited by the authors. Furthermore, Egermayer2 described that “benefits resulting from the use of heparin and oral anticoagulants to treat DVT are more likely to be caused by reduction of the rate of recurrence than to any significant direct local effects on established thrombosis… trials of anticoagulant therapy for thromboembolic disease do not support the belief that this treatment significantly inhibits thrombus propagation.” This is well exemplified by the following: “patients treated with conventional anticoagulant therapy for deep venous thrombosis show either no change or thrombus extension in the first few months in approximately 50% of cases.”2 The studies included in the most recent meta-analysis3 cited by Hillegass and colleagues found that 10 of the 13 trials initiated ambulation on day zero. Importantly, none of those 10 trials specified delaying mobilization until a therapeutic level of anticoagulation was achieved. One study even described that “patients were motivated to keep or resume walking immediately and were encouraged to undertake strolls in the hospital gardens.” Notably, low-molecular-weight heparin was the anticoagulant of choice in all 13 trials (except 1 trial that did not describe the details). Because it takes only 3 to 5 hours for low–molecular-weight heparin to achieve peak therapeutic levels, readers of these trials may interpret that patients were already therapeutic on anticoagulation prior to mobilization. In 2012, the American College of Chest Physicians (ACCP) VTE guideline stated, “we suggest early ambulation (eg, without a period of bed rest) when feasible because of its potential to decrease post thrombotic syndrome and improve quality of life.”4 Meanwhile, Streiff et al concluded that “the existing literature suggest that ambulation in patients with acute DVT/PE is safe as soon as therapeutic anticoagulation is achieved,” reflecting on the same 4 trials examined by the ACCP.5 This illustrates how the literature has been interpreted differently. To our knowledge, no previous study has compared the risk of pulmonary embolism in patients mobilized with and without therapeutic anticoagulation. In patients without contraindications to low–molecular-weight heparin, fondaparinux, or direct oral anticoagulants, the consequences of withholding mobilization for 2 to 5 hours may be trivial. Yet, the duration of bed rest could quickly extend >24 hours depending on the time of diagnosis and local mobility practices. Such recommendations could delay important physical therapist treatment while exposing patients to significant risks from immobility, including further VTE. The waiting approach is particularly concerning in patients who require unfractionated heparin, such as patients who are in the intensive care unit, have renal failure, or have conflicting bleeding risks that require careful titration of anticoagulation. Some patients could take days to achieve a therapeutic level due to heparin resistance. For certain patients, the medical team may opt for a lower activated partial thromboplastin clotting time (aPTT) target to balance the bleeding risks, thus never achieving a therapeutic level. Should we allow prolonged immobility in these patients because of the theoretical risk of pulmonary embolism? Benefits of early mobilization are well established, especially among patients who are critically ill. The current literature seems to favor prompt mobilization without any period of waiting. The following clinical scenarios highlight the controversy: Consider an ambulatory patient seen in an outpatient physical therapy clinic after an orthopedic surgery with a suspected lower extremity DVT. Should this patient be immobilized and transported to the emergency department via stretcher and ambulance? A hospitalized patient is waiting on the result of duplex ultrasound to rule out lower extremity DVT. Mobility and therapy are held, given the concern for DVT, but in the absence of confirmatory ultrasound, anticoagulation has yet to be started. DVT is ultimately confirmed, but the next morning the patient is below the therapeutic target of anticoagulation. Is it feasible for a therapist to monitor this patient’s laboratory values throughout the day to determine when to mobilize? Is it acceptable to continue to immobilize this patient and further delay therapy? The primary literature on mobilization in VTE does not specifically call for a delay in mobility until therapeutic levels of anticoagulation are achieved. At one of our institutions, there is no restriction on mobility in suspected or confirmed VTE based on initiation or achievement of therapeutic levels of anticoagulation. The harm of immobility is extensive and well established, as are the barriers to mobility in hospitalized patients. Any recommendation to restrict mobility in the absence of strong evidence to support bed rest should be interpreted with caution. We suggest that the readers of the current guideline recognize the ongoing debate and consider mobilization before the initiation of anticoagulation or with subtherapeutic anticoagulation, especially in cases in which immobility harm outweighs the theoretical risk of pulmonary embolism. Concept/idea/research design: K. Venere, K. Ridgeway, M. Fuchita Writing: K. Venere, K. Ridgeway, R.L. Page II, M. Fuchita Project management: K. Ridgeway Consultation (including review of manuscript before submitting): K. Ridgeway, R.L. Page II The authors completed the ICMJE Form for Disclosure of Potential Conflicts of Interest and reported no conflicts of interest.