Individualized Thromboprophylaxis in Patients with Lower-Leg Cast Immobilization—A Validation and Subgroup Analysis in the POT-CAST TrialFunding This project received funding from ZonMW VIMP grant, project number 17110200011 and Trombose stichting, project number 2016–02.
11 February 2019
24 May 2019
28 July 2019 (online)
Background A small subgroup of patients treated with lower-leg cast immobilization develops venous thromboembolism (VTE).
Objectives (1) Identify risk factors for VTE in patients with cast immobilization, (2) assess the effectiveness of thromboprophylaxis in low- and high-risk groups, and (3) validate the performance of the L-TRiP(cast) score.
Methods Data from the POT-CAST trial were used. A total of 1,519 patients with lower-leg cast immobilization were randomized to a prophylactic dose of low-molecular-weight heparin or no treatment. Primary outcome: symptomatic VTE within 3 months. Absolute risks (ARs) were determined for low- and high-risk subgroups. For several risk factors, relative risks (RRs) for VTE were estimated with corresponding 95% confidence intervals (CIs). For validating the L-TRiP(cast) score, a discrimination and calibration analysis were performed.
Results Patients with a body mass index of > 30 kg/m2 and those with a VTE in their family history had an increased VTE risk, RR 3.8 (95% CI, 1.5–9.4) and RR 2.4 (95% CI, 1.0–5.6), respectively. Concerning injury-specific risk factors, patients with an Achilles tendon rupture or those who were surgically treated had the highest risk of VTE, AR at 8.5% (95% CI, 3.7–16.1) and AR 3.5% (95% CI, 1.3–7.5), respectively. There were no subgroups in which thromboprophylaxis was effective for prevention of symptomatic VTE. The area under the curve for the L-TRiP(cast) score was 0.69 (95% CI, 0.58–0.80).
Conclusion Thromboprophylaxis was not effective for VTE prevention following lower-leg cast immobilization in any risk category. Low- and high-risk individuals could be identified using the L-TRiP(cast) score. The best treatment strategy for these patients is yet to be determined.
B.N. and S.C. designed the analysis. B.N. and R.v.A. included patients. B.N. and S.L.C. performed the statistical analyses. B.N. wrote the first manuscript draft. All authors were involved in writing and revision of the manuscript. All authors read and approved the final manuscript.
All participants provided written informed consent. This study was approved by the Medical Ethical Committee of the Leiden University Medical Center in Leiden, The Netherlands.
- 1 Nemeth B, Cannegieter SC. Venous thrombosis following lower-leg cast immobilization and knee arthroscopy: From a population-based approach to individualized therapy. Thromb Res 2019; 174: 62-75
- 2 van Adrichem RA, Nemeth B, Algra A. , et al; POT-KAST and POT-CAST Group. Thromboprophylaxis after knee arthroscopy and lower-leg casting. N Engl J Med 2017; 376 (06) 515-525
- 3 Knudson MM, Ikossi DG, Khaw L, Morabito D, Speetzen LS. Thromboembolism after trauma: an analysis of 1602 episodes from the American College of Surgeons National Trauma Data Bank. Ann Surg 2004; 240 (03) 490-496
- 4 van Adrichem RA, Debeij J, Nelissen RG, Schipper IB, Rosendaal FR, Cannegieter SC. Below-knee cast immobilization and the risk of venous thrombosis: results from a large population-based case-control study. J Thromb Haemost 2014; 12 (09) 1461-1469
- 5 Kock HJ, Schmit-Neuerburg KP, Hanke J, Rudofsky G, Hirche H. Thromboprophylaxis with low-molecular-weight heparin in outpatients with plaster-cast immobilisation of the leg. Lancet 1995; 346 (8973): 459-461
- 6 Lapidus LJ, Rosfors S, Ponzer S. , et al. Prolonged thromboprophylaxis with dalteparin after surgical treatment of Achilles tendon rupture: a randomized, placebo-controlled study. J Orthop Trauma 2007; 21 (01) 52-57
- 7 Riou B, Rothmann C, Lecoules N. , et al. Incidence and risk factors for venous thromboembolism in patients with nonsurgical isolated lower limb injuries. Am J Emerg Med 2007; 25 (05) 502-508
- 8 Lapidus LJ, Ponzer S, Elvin A. , et al. Prolonged thromboprophylaxis with Dalteparin during immobilization after ankle fracture surgery: a randomized placebo-controlled, double-blind study. Acta Orthop 2007; 78 (04) 528-535
- 9 Kujath P, Spannagel U, Habscheid W. Incidence and prophylaxis of deep venous thrombosis in outpatients with injury of the lower limb. Haemostasis 1993; 23 (Suppl. 01) 20-26
- 10 Lassen MR, Borris LC, Nakov RL. Use of the low-molecular-weight heparin reviparin to prevent deep-vein thrombosis after leg injury requiring immobilization. N Engl J Med 2002; 347 (10) 726-730
- 11 Nemeth B, van Adrichem RA, van Hylckama Vlieg A. , et al. Venous thrombosis risk after cast immobilization of the lower extremity: derivation and validation of a clinical prediction score, L-TRiP(cast), in three population-based case-control studies. PLoS Med 2015; 12 (11) e1001899
- 12 Schulman S, Angerås U, Bergqvist D, Eriksson B, Lassen MR, Fisher W. ; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients. J Thromb Haemost 2010; 8 (01) 202-204
- 13 van Buuren S, Boshuizen HC, Knook DL. ; van BS. Multiple imputation of missing blood pressure covariates in survival analysis. Stat Med 1999; 18 (06) 681-694
- 14 Steyerberg EW, Vickers AJ, Cook NR. , et al. Assessing the performance of prediction models: a framework for traditional and novel measures. Epidemiology 2010; 21 (01) 128-138
- 15 Zee AA, van Lieshout K, van der Heide M, Janssen L, Janzing HM. Low molecular weight heparin for prevention of venous thromboembolism in patients with lower-limb immobilization. Cochrane Database Syst Rev 2017; 8: CD006681
- 16 Hickey BA, Watson U, Cleves A. , et al. Does thromboprophylaxis reduce symptomatic venous thromboembolism in patients with below knee cast treatment for foot and ankle trauma? A systematic review and meta-analysis. Foot Ankle Surg 2018; 24 (01) 19-27
- 17 Horner D, Pandor A, Goodacre S, Clowes M, Hunt BJ. Individual risk factors predictive of venous thromboembolism in patients with temporary lower limb immobilization due to injury: a systematic review. J Thromb Haemost 2019; 17 (02) 329-344
- 18 Heyes GJ, Tucker A, Michael AL, Wallace RG. The incidence of deep vein thrombosis and pulmonary embolism following cast immobilisation and early functional bracing of Tendo Achilles rupture without thromboprophylaxis. Eur J Trauma Emerg Surg 2015; 41 (03) 273-276
- 19 Blanco JA, Slater G, Mangwani J. A prospective cohort study of symptomatic venous thromboembolic events in foot and ankle trauma: the need for stratification in thromboprophylaxis?. J Foot Ankle Surg 2018; 57 (03) 484-488
- 20 Saragas NP, Ferrao PN, Saragas E, Jacobson BF. The impact of risk assessment on the implementation of venous thromboembolism prophylaxis in foot and ankle surgery. Foot Ankle Surg 2014; 20 (02) 85-89
- 21 Nemeth B, Timp JF, van Hylckama Vlieg A, Rosendaal FR, Cannegieter SC. High risk of recurrent venous thrombosis in patients with lower-leg cast immobilization. J Thromb Haemost 2018; 16 (11) 2218-2222