Andrew J. Hughes, Jayaramaraju Dheenadhayalan, Svetlana Bozhkova, Aleksandar Lesic, Nagashree Vasudeva, Alina Kasimova, Punaganapathi Sundaram Velmurugesan, Jamino Ahn, Chad A. Krueger.

Response/Recommendation: Mechanical and pharmacological venous thromboembolism (VTE) prophylaxes are advised for patients undergoing internal fixation of a hip fracture, following an individualized risk assessment. In the setting of surgical delays, preoperative pharmacological prophylaxis should be considered. Pharmacological thromboprophylaxis should continue throughout the persistent postoperative prothrombotic state, commencing 12 hours post wound closure, and continuing for at least 28 days.

Strength of Recommendation: Moderate

Rationale: Patients sustaining hip fracture are subjected to a risk of VTE quoted at over 30% within the literature^1–4. Advancements in thromboprophylaxis have reduced the overall rates of clinically relevant VTE to less than 4%^5–8. The goals of VTE prophylaxis within this at-risk cohort are to prevent fatal pulmonary embolism (PE) and reduce the incidence of post-VTE morbidity, both of which contribute to the significant in-hospital and one-year mortality rates^9–11. Despite widespread awareness of the merits of thromboprophylaxis, variability in practice patterns persist, owing to a lack of available high-quality evidence^12–15. As such, published clinical practice guidelines (CPG) have made efforts to highlight the standards required of healthcare providers so as to mitigate VTE risk within the hip fracture population^6,15–18.

On admission, it is advised that hip fracture patients undergo medical optimization, adequate hydration and receive mechanical prophylaxis, using graduated compression stockings (GCS) or intermittent pneumatic compression devices (IPCD), ensuring correct application, provided no contraindications are identified^{6,16,17,19,20}. Pharmacological prophylaxis should be considered preoperatively if surgical delays are anticipated, commenced ideally within 14 hours of admission, following a comprehensive bleeding and thrombosis risk assessment²¹. Appropriate preoperative agents include either low-molecular-weight heparin (LMWH), with the last dose administered no less than 12 hours preoperatively, or unfractionated heparin (UFH) with close serological monitoring, particularly in patients requiring weight or renal adjusted formulations^16,21,22. Fondaparinux use has been historically suggested, however its use has been more recently cautioned preoperatively given its known protracted onset of action, and the need for 24 hours to ensure adequate pharmacological clearance. In addition to mechanical and chemical thromboprophylaxis, early definitive internal fixation is favored, so as to mitigate the crescendo effect of delayed surgical intervention on VTE risk, whilst also minimizing the period of preoperative bed-rest^5,23,24.

Postoperatively, mechanical prophylaxis should take the form of early mobilization, coupled with continuous GCS or IPCD use for the duration of stay in both the acute hospital and post-discharge rehabilitation settings^18,19,25,26. Choice of GCS length, either knee-length or thigh-length, should rely on patient compliance, preference, and local skin condition, as no significant difference has been identified to date between either in preventing postoperative VTE²⁷. Mechanical prophylaxis has also been advised to continue, for at least 18 hours per day, until a level of mobility is achieved resembling the patient’s pre-admission status^16,19,20.

The published CPG all agree that pharmacological prophylaxis, in combination with mechanical prophylaxis, is required to prevent fatal PE and post-VTE morbidity. Postoperatively, it is suggested that the first prophylactic dose should be administered no sooner than 12 hours post wound closure^16,18,28,29. Agents proven to be efficacious in the setting of hip fractures include LMWH, UFH, fondaparinux, adjusted-dose vitamin K antagonists and aspirin (ASA)⁶. Agent selection should be based on patient parameters, healthcare provider preferences and a shared decision. Therapy should continue for a minimum of 10 to 14 days, with most recommendations within CPG to continue for at least 28 to 35 days postoperatively, in light of the persistently elevated postoperative VTE risk^{4,7,16,18,28,30,31}. LMWH or UFH are often utilized in the early postoperative period in clinical practice, given their parenteral preparations and reliable pharmacokinetics⁵.

To date, a leading pharmacological agent has yet to be defined. LMWH has been established as the prophylactic agent against which novel medications are compared⁶. The American College of Chest Physicians (ACCP), and the American Society of Hematology (ASH) guidelines both specifically advocate for a full extended prophylactic course of LMWH in the setting of a hip fracture, despite surgeon reservations surrounding the need for administration education, as well as the inconvenience of daily subcutaneous injections^6,18. Fondaparinux has demonstrated equivocal VTE rates to LMWH but has been cautioned in light of major bleeding rates experienced by frail patients weighing less than 50 kilograms^6,32. Warfarin, a vitamin K antagonist, has not demonstrated significant benefits compared to LMWH in the hip fracture population to date. Safety concerns with warfarin remain, particularly in relation to management of the international normalized ratio (INR) perioperatively, contributions to surgical delays due to prolonged clearance, slow-onset on action, and drug interactions affecting its efficacy^5,6,29,33,34. Rivaroxaban, dabigatran, and apixaban have been approved for use against VTE in the setting of total joint arthroplasty but have not yet been sufficiently evaluated in the setting of hip fractures. Recent studies, one of retrospective nature, and one randomized controlled trial with small sample sizes in all study groups, demonstrated encouraging results with direct oral anticoagulant (DOAC) use, however further evidence is required before clinical practice is influenced^35,36. ASA has been shown to significantly reduce VTE rates throughout the high-risk post-fracture time period compared to placebo, but routine ASA use remains controversial, given the lack of evidence to support equivalence to LMWH proven efficacy^37,38. ASA and DOAC use have come under investigation of late. Two heterogenous meta-analyses, recently published, suggest favorable findings with regards to VTE reduction, however level one evidence is yet to emerge^39,40. Both agents are convenient given their more simplistic oral regimens and encouragingly low rates of VTE, but reservations persist concerning hemorrhagic events, particularly in the immediate postoperative period^34,41.

A clear consensus amongst CPG is unfortunately lacking regarding the optimal pharmacological agent, dose, and duration. Concerns surround balancing the susceptibility of hip fracture patients to VTE, with the rate of wound complications and significant hemorrhagic events⁴². Despite recent advancements in enhanced recovery programs, clinical care pathways, and national audit programs, which have combined to improve the standard of hip fracture care worldwide, VTE CPG continue to reference evidence stemming from the 1990’s and 2000’s. As such, focusing future research efforts on well-designed high-quality trials is of utmost importance, so as to clarify a consensus on means to reliably prevent VTE in the hip fracture population, and facilitate the publication of guidelines that will positively influence clinical practice.

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