Thromboprophylaxis in Non-operative Lower-Limb Immobilization: Risk Stratification Identifies Whom to Spare, Not Whom to Treat - A Narrative Review.

Abstract

Introduction: Temporary lower-limb immobilization after injury is an established risk factor for venous thromboembolism (VTE), yet recommendations for non-operatively managed patients remain discordant. Secondary literature in this field commonly asserts that pharmacological prophylaxis, while unnecessary as a routine, is effective in patients identified as high risk. The aims of this review were to (i) determine whether that assertion is supported by primary randomized evidence, and (ii) define what validated risk assessment models can and cannot currently be used to justify.

Materials and methods: Narrative review prepared in accordance with the Scale for the Assessment of Narrative Review Articles and published guidance on narrative review methodology; the full search string and eligibility criteria are reported in Material and Methods. PubMed/MEDLINE was searched to June 2026 for randomized trials, systematic reviews and network meta-analyses, prospective multicenter cohorts, risk model derivation and validation studies, and guidelines addressing VTE prophylaxis in temporary lower-limb immobilization. Every source was checked against its own stated conclusions. A claim of treatment efficacy in a defined population was accepted only where supported by a randomized comparison against no prophylaxis within that population.

Results: In unselected patients, the Prevention of Thrombosis after Lower Leg Plaster Cast (POT-CAST) trial found no reduction in symptomatic VTE with low-molecular-weight heparin (1.4% vs. 1.8%; relative risk 0.8, 95% confidence interval [CI] 0.3-1.7). Meta-analyses do demonstrate reductions in asymptomatic and composite endpoints, but the older trials contributing to them used mandatory screening, and network meta-regression identified no treatment effect modifier other than the agent used. The validation and subgroup analysis of POT-CAST found no risk category in which prophylaxis was effective, despite confirming markedly elevated absolute risk in some strata, including 8.5% (95% CI 3.7-16.1) after Achilles tendon rupture. CASTING confirmed prospectively that anticoagulation can be withheld below a thrombosis risk prediction for patients with cast immobilization TRiP(cast) score of seven, with symptomatic VTE of 0.7% (95% CI 0.3-1.4), but every patient above the threshold was treated, so the trial cannot estimate efficacy in that group; in the TILLIRI cohort, 846 anticoagulated patients scoring below seven sustained no symptomatic VTE. Elevated baseline risk and treatment benefit are therefore separate constructs requiring separate evidence.

Conclusion: Current evidence establishes risk stratification as an instrument for de-escalation rather than escalation, since roughly three-quarters of immobilized patients can be identified as low risk and safely left untreated. In the high-risk minority, prophylaxis remains reasonable and permitted by guidance but is unproven for symptomatic VTE and should be offered as such. The priority trial is prophylaxis versus no prophylaxis in score-defined high-risk patients, not a comparison between agents.