150 – Do pediatric patients placed in a lower extremity cast immobilization require routine VTE prophylaxis?

Manjeera Rednam, Ashok Johari, Sanjeev Sabharwal.

Response/Recommendation: Routine thromboprophylaxis is not recommended in pediatric patients with cast immobilization. Furthermore, young age is protective against deep venous thrombosis (DVT) in children. Unlike the adult population, the association between lower extremity cast immobilization and venous thromboembolism (VTE) risk has not been established in children. As development of acute DVT is unusual in children, routine prophylaxis is not recommended. However, there are also no clear recommendations for children with more than 3 risk factors for the development of VTE.

Strength of recommendation: Weak.

Rationale: The presence of specific thromboembolic risk factors such as older age, along with the nature of extremity injury, are the main determinants when deciding whether to administer thromboprophylaxis in patients with lower leg trauma immobilized in a cast or a splint^1-3.

Amongst pediatric trauma inpatients, those aged 16 to 21 years had a 4-fold increase in risk of VTE development, compared to patients 12 years or younger. Additionally, patients aged 16 to 21 years also had significantly higher odds of VTE development compared to those aged 13 to 15 years. Furthermore, no association of significance was identified between patients’ age and injury severity. Clinical screening for risk of VTE may be applied to older age groups (³ 13 years). In addition, a VTE prophylaxis protocol must be implemented in patients > 16 years old, as the risk of VTE increases most dramatically at 16 years, after a smaller increase at 13 years⁴.

The association between VTE and altered mobility has been demonstrated in adult patients. However, there is paucity of data on VTE following cast immobilization in children. Decreased mobility, even without the use of a cast, is known to increase the risk of DVT. Similarly, immobilization for longer than 3 days (p < 0.0001) and hospitalization for ³ 7 days (p < 0.0001), are potential risk factors for VTE development in admitted pediatric patients (< 20 years old)⁵. The definition of ‘immobilization’ is challenging in children as younger infants may not necessarily be ambulatory. Further evidence-based on prospective studies is necessary to validate these findings.

Oral contraceptive (OCP) use is a common risk factor for VTE in adolescent females. Long travel, immobilization, plaster cast, and/or trauma are all transient risk factors that can trigger VTE events in OCP users⁶.

Common risk factors for VTE in adults with inherited thrombophilia do not seem to increase the thrombotic risk in children who are carriers of their parents’ mutated gene. Screening for thrombophilia in otherwise healthy children (< 15 years old) with have a family history of coagulation disorders seems unjustified⁷.

The 2017 Polish Consensus Statement (PCS) does not recommend routine thromboprophylaxis in patients with lower limb trauma immobilized by the use of a plaster cast (class C recommendation)⁸. Their findings have since been validated by several studies^9-12. On the other hand, the PCS does recommend VTE prophylaxis in moderate to high VTE risk patients immobilized following lower limb trauma. Additionally, they recommend the administration of low-molecular-weight heparin (LMWH) in this patient population. Furthermore, prophylactic LMWH is recommended for the duration of immobilization, and for 5 – 7 days afterwards. However, all the above recommendations are based on studies in adult populations. Currently, no studies suggest the above in the pediatric age group.

Testroote et al., recommended that all adult patients treated with cast immobilization be considered to receive VTE prophyalxis^1,13-15. However, based on the limited available literature, the incidence of VTE in patients receiving cast immobilization is not large enough to justify pharmacological prophylaxis in all these patients, as the additional costs and bleeding risks associated with pharmacotherapy must also be considered (0.3% major bleeding)¹⁶.

Haque et al., developed a patient questionnaire based on the National Institute for Health and Care Excellence (NICE) in-patient guidelines as well as the UK College of Emergency Medicine (CEM) outpatient guidelines. Ambulatory outpatients being managed with cast immobilization for foot and ankle fractures were the primary target of this questionnaire. Risk factors included: age > 65 years, above-knee plaster cast, long-travel in cast, hormone replacement therapy or estrogen-containing contraceptive, varicose veins, active (heart, lung, bowel, or joint) disease, body mass index (BMI) > 30 kg/m², personal history of blood clot, first-degree family history of blood clot, known thrombophilia, pregnant or within 6 weeks of childbirth, hospital admission within the last six weeks, active cancer or receiving cancer treatment (including tamoxifen and raloxifene), and achilles tendon rupture. Patients were classified as high- or low-risk for VTE and administered LMWH accordingly¹⁷. Additionally, the Leiden–Thrombosis Risk Prediction score (L-TRiP cast) was developed for adult patients with cast immobilization and has a cutoff of 10 points to stratify individuals into high- vs. low-risk categories¹⁶. This score was developed with data from the Multiple Environmental and Genetic Assessment (MEGA) study of risk factors for venous thrombosis and includes patients 18 to 70 years old. Further studies are required to develop similar risk prediction models in children. The difference in pathophysiology of coagulation in children, compared to their adult counterparts, seems to confer protection against VTE in younger patients.

Given the low incidence of VTE in the pediatric population, the risks associated with routine VTE prophylaxis administration, and lack of available evidence to recommend regular screening, routine VTE prophylaxis cannot be recommended in pediatric patients treated with cast immobilization. As has been done in the past for the adult population, research efforts should focus on the development of evidence-based risk-stratification models that include a recommendation for the type and duration of VTE prophylactic agent in pediatric patients receiving cast immobilization.

References:

1.         Decramer,Arne &Lowyck, Hans &Demuynck, Marc. (2008). Parameters influencing thromboprophylaxis management of a lower leg trauma treated with a cast/splint. Acta OrthopaedicaBelgica. 74. 672-7.

2.         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 ThrombHaemost. 2019 Feb;17(2):329-344. doi: 10.1111/jth.14367. Epub 2019 Feb 7. PMID: 30580466; PMCID: PMC6392108.

3.         Kocialkowski C, Bhosale A, Pillai A. Venous thromboembolism prophylaxis in patients immobilised in plaster casts. Clin Res. 2016;4(3).10.4172/2329-910X.1000203.

4.         Van Arendonk KJ, Schneider EB, Haider AH, Colombani PM, Stewart FD, Haut ER. Venous Thromboembolism After Trauma: When Do Children Become Adults? JAMA Surg. 2013;148(12):1123–1130. doi:10.1001/jamasurg.2013.3558

5.         Sharathkumar AA, Mahajerin A, Heidt L, Doerfer K, Heiny M, Vik T, Fallon R, Rademaker A. Risk-prediction tool for identifying hospitalized children with a predisposition for development of venous thromboembolism: Peds-Clot clinical Decision Rule. J ThrombHaemost. 2012 Jul;10(7):1326-34. doi: 10.1111/j.1538-7836.2012.04779. x. PMID: 22583578.

6.         Dulícek P, Malý J, Pecka M, Beránek M, Cermáková E, Malý R. Venous thromboembolism in young female while on oral contraceptives: high frequency of inherited thrombophilia and analysis of thrombotic events in 400 Czech women. Clin Appl ThrombHemost. 2009 Oct;15(5):567-73. doi: 10.1177/1076029608325544. Epub 2008 Dec 30. PMID: 19117968.

7.         Daniela Tormene, Paolo Simioni, Paolo Prandoni, Francesca Franz, PatriziaZerbinati, Giulio Tognin, Antonio Girolami; The incidence of venous thromboembolism in thrombophilic children: a prospective cohort study. Blood 2002; 100 (7): 2403–2405. doi: https://doi.org/10.1182/blood-2002-04-1186

8.         Tomkowski, Witold &Kuca, Paweł&Urbanek, T. & Chmielewski, Dariusz&Krasiński, Zbigniew &Pruszczyk, Piotr &Windyga, J. &Oszkinis, Grzegorz &Jawien, Arkadiusz &Burakowski, Janusz&Dybowska, Małgorzata&Kesik, Jan &Zubilewicz, Tomasz. (2017). Venous thromboembolism — recommendations on the prevention, diagnostic approach and management. The 2017 Polish Consensus Statement. Acta Angiologica. 23. 35-71. 10.5603/AA.2017.0008.

9.         Giannadakis K, Gehling H, Sitter H, Achenbach S, Hahne H, Gotzen L. IsteinegenerellemedikamentöseThromboembolie prophylaxes beiambulanterTherapie von Verletzungen der unterenExtremitätimimmobilisierendenUnterschenkelstützverbandnotwendig? [Is a general pharmacologic thromboembolism prophylaxis necessary in ambulatory treatment by plaster cast immobilization in lower limb injuries?]. Unfallchirurg. 2000 Jun;103(6):475-8. German. doi: 10.1007/s001130050568. PMID: 10925650.

10.       Lapidus LJ, Ponzer S, Elvin A, Levander C, Lärfars G, Rosfors S, de Bri E. Prolonged thromboprophylaxis with Dalteparin during immobilization after ankle fracture surgery: a randomized placebo-controlled, double-blind study. Acta Orthop. 2007 Aug;78(4):528-35. doi: 10.1080/17453670710014185. PMID: 17966008.

11.       Gehling H, Leppek R, Künneke M, Gotzen L, Giannadakis K, Henkel J. IsteineThromboembolieprophylaxebeiambulanter und konservativerTherapie der fibularenBandruptur des oberenSprunggelenkserforderlich? [Is prevention of thromboembolism in ambulatory and conservative therapy of rupture of the fibular ligament of the upper ankle joint necessary?]. Unfallchirurg. 1994 Jul;97(7):362-5. German. PMID: 7939738.

12.       Selby R, Geerts WH, Kreder HJ, Crowther MA, Kaus L, Sealey F. Symptomatic venous thromboembolism uncommon without thromboprophylaxis after isolated lower-limb fracture: the knee-to-ankle fracture (KAF) cohort study. J Bone Joint Surg Am. 2014 May 21;96(10): e83. doi: 10.2106/JBJS.M.00236. PMID: 24875035.

13.       Healy B, Beasley R, Weatherall M. Venous thromboembolism following prolonged cast immobilisation for injury to the Tendo Achilles. J Bone Joint Surg Br. 2010 May;92(5):646-50. doi: 10.1302/0301-620X.92B5.23241. PMID: 20436000.

14.       Testroote M, Stigter W, de Visser DC, Janzing H. Low molecular weight heparin for prevention of venous thromboembolism in patients with lower-leg immobilization. Cochrane Database Syst Rev. 2008 Oct 8;(4):CD006681. doi: 10.1002/14651858.CD006681.pub2. Update in: Cochrane Database Syst Rev. 2014;4:CD006681. PMID: 18843725.

15.       Zee AAG, van Lieshout K, van der Heide M, Janssen L, Janzing HMJ. Low molecular weight heparin for prevention of venous thromboembolism in patients with lower‐limb immobilization. Cochrane Database of Systematic Reviews 2017, Issue 8. Art. No.: CD006681. DOI: 10.1002/14651858.CD006681.pub4.

16.       Nemeth B, van Adrichem RA, van HylckamaVlieg 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. Published 2015 Nov 10. doi: 10.1371/journal.pmed.1001899

17.       Haque S, Bishnoi A, Khairandish H, Menon D. Thromboprophylaxis in Ambulatory Trauma Patients with Foot and Ankle Fractures: Prospective Study Using a Risk Scoring System. Foot Ankle Spec. 2016 Oct;9(5):388-93. doi: 10.1177/1938640016640892. Epub 2016 Apr 4. PMID: 27044599.