Cecilia Méndez, Juan Del Castillo, Eduardo Vilensky, Muhammad Amin Chinoy, Syeda Mehwish.
Response/Recommendation: In the absence of other identifiable risk factors of venous thromboembolism (VTE), chemoprophylaxis for VTE should not be routinely prescribed in patients younger than thirteen undergoing orthopaedic procedures.
Strength of Recommendation: Weak.
Rationale: VTE, a disease process that encompasses both deep venous thrombosis (DVT) and pulmonary embolism (PE), is well-studied in the adult population. However, in the pediatric orthopaedic population, VTE occurrence is still rare. Recent estimates have placed the incidence of post-operative VTE in this setting to be between 0.05 – 0.1%1. Due to a paucity of evidence recommending routine pharmacologic prophylaxis for pediatric orthopaedic patients, we attempted to identify the reported incidence of VTE in certain “high-risk” orthopaedic procedures in the pediatric population.
In a study of the Pediatric Health Information System (PHIS) database, Georgopoulos et al.2, reported a VTE incidence of 0.063% in pediatric patients undergoing elective orthopaedic procedures. However, this database can result in a gross underestimation of the true incidence of VTE. Furthermore, after conducting a multivariate analysis, no single elective procedure was identified as significantly increasing the risk of VTE. In another study of the National Surgical Quality Improvement Program (NSQIP) database, the incidence of VTE, DVT, and PE in pediatric orthopaedic patients was 0.1%, 0.09%, and 0.01%, respectively. Additionally, the highest prevalence of VTE was reported in patients undergoing infection-related procedures3.
In two separate studies, VTE rates in pediatric patients undergoing knee arthroscopy were reported to be between 0.25% to 0.27%. Additionally, they found that the majority of VTE events occurred in patients with known predisposing risk factors4,5. In a another study, Allahabadi et al.6, reported that the incidence of VTE was 0.61% in adolescents who underwent a pelvic osteotomy. Surprisingly, of the nine patients that developed VTE, nearly half (4/9 patients) had received pharmacologic prophylaxis postoperatively.
In a study of the PHIS database, Shore et al.7, found that the incidence of VTE after elective spine and hip surgery in children with neuromuscular disorders was 0.04%. Furthermore, both patients who experienced a VTE event had a prior diagnosis of a coagulation disorder. Therefore, in the absence of known risk factors, the administration of VTE chemoprophylaxis in this setting may be unnecessary.
In a survey of Scandinavian scoliosis centers between 1963 and 1976, the reported incidence of DVT was 0.65%8. In another study, follow-up doppler ultrasonography was performed on 40 consecutive post pubertal adolescents undergoing posterior spinal instrumentation. Of the 40 patients, two cases of transient thromboses were identified, both of which resolved spontaneously9. Additionally, in a study of 1,471 pediatric patients undergoing scoliosis surgery, Erkilinc et al.10, reported that the incidence of DVT was 0.13%. Therefore, the authors concluded that mechanical prophylaxis was sufficient in this setting. Furthermore, in a study of the National Inpatient Sample (NIS) database, Jain et al.11, found that in pediatric patients undergoing spine surgery, the incidence of DVT was 0.21%. In addition, when compared to children with idiopathic scoliosis, those with congenital, syndromic or traumatic etiology experienced a higher incidence of VTE12.
Several studies have evaluated the incidence of VTE in pediatric trauma patients. In a study of the PHIS database, Murphy et al.13, found that the incidence of VTE in patients with lower-extremity trauma was 0.058%. Conversely, in another study utilizing the Kid’s Inpatient Database (KID), the incidence of VTE in pediatric orthopaedic trauma patients was 0.68%. However, incidence of VTE in pediatric patients with isolated fractures of the lower-limbs was 0.25%, compared to 0.32% in patients with pelvic injuries14. In another study, Greenwald et al.12, found that over a 20-year period the incidence of DVT in patients with pelvic and femoral fractures was 0.17%. Additionally, there were no reported cases of PE or mortality secondary to VTE. Moreover, Internal fixation of lower limb fractures is commonly quoted as a risk factor for VTE development15. Despite this, we did not find any data to support this claim.
Current data suggest that the incidence of VTE in pediatric patients is highest during adolescence3. Similarly, a recent follow-up survey of the Pediatric Orthopaedic Society of North America (POSNA) for 46 VTE cases found that the average age at diagnosis was 14.3 years16. In addition, Murphy et al.5, found that patients that experienced a VTE event were 15 to 18 years old and had at least one other identifiable risk factor for VTE. These included: oral contraceptive (OCP) use, smoking, obesity, an arthroscopically assisted open procedure, or tourniquet time > 60 minutes. Furthermore, two separate studies with large cohorts identified age as a statistically significant independent risk factor for the development of VTE. O’Brien et al.17, identified 14 years of age as the threshold for increased VTE risk. Additionally, Vavilala et al.15, found that there was a 5-fold increase in risk of DVT between the ages of 10 and 15. Moreover, Meier et al.18, recently established the Best Evidence Statement (BESt) clinical practice guidelines (CPG) for VTE prophylaxis in children. They found that age > 10 years and altered mobility were the two most important factors when considering initiating VTE prophylaxis.
Several studies have shown that the presence of a CVC carries the single greatest risk for DVT development in the pediatric population. Furthermore, some studies have estimated that 33% to 80% of all pediatric DVT can be attributed to the presence of a CVC10,19–22.
In a retrospective case-control study, Stokes et al.23, demonstrated a correlation between obesity and DVT. They found that obese pediatric patients were 2.1-times more likely to experience a VTE event, compared to non-obese patients. Similarly, a recent large database study demonstrated an increased risk of DVT in obese patients compared to nonobese patients24.
Infection a common and well-established risk factor for the development of VTE3,25,26. Extensive septic thrombosis is associated with infections caused by microorganisms producing necrotizing toxins such as Panton-Valentine leucocidin (PVL). In conclusion, infection with methicillin-resistant Staphylococcus aureus infection justifies the use of VTE thromboprophylaxis25.
The low incidence of DVT, heterogeneity of available clinical studies, multiplicity of risk factors, and age-related variability in risk levels has made it difficult to establish evidence-based guidelines for chemoprophylaxis in pediatric patients undergoing orthopaedic procedures. In conclusion, thromboprophylaxis should be considered in adolescents with additional identifiable risk factors. Specifically, thromboprophylaxis should be considered in pediatric patients with osteomyelitis or disseminated infection and in pediatric patients with a central line.
References:
1. Padhye K, El-Hawary R, Price V, Stevens S, Branchford B, Kulkarni K. Development of a perioperative venous thromboembolism prophylaxis algorithm for pediatric orthopedic surgical patients. Pediatr Hematol Oncol. 2020;37(2):109-118. doi:10.1080/08880018.2019.1695030
2. Georgopoulos G, Hotchkiss MS, McNair B, Siparsky G, Carry PM, Miller NH. Incidence of Deep Vein Thrombosis and Pulmonary Embolism in the Elective Pediatric Orthopaedic Patient. J Pediatr Orthop. 2016;36(1):101-109. doi:10.1097/BPO.0000000000000391
3. Baker D, Sherrod B, McGwin G, Ponce B, Gilbert S. Complications and 30-day Outcomes Associated With Venous Thromboembolism in the Pediatric Orthopaedic Surgical Population. J Am Acad Orthop Surg. 2016;24(3):196-206. doi:10.5435/JAAOS-D-15-00481
4. Lau BC, Jagodzinski J, Pandya NK. Incidence of Symptomatic Pulmonary Embolus and Deep Vein Thrombosis After Knee Arthroscopy in the Pediatric and Adolescent Population. Clin J Sport Med. 2019;29(4):276-280. doi:10.1097/JSM.0000000000000519
5. Murphy RF, Heyworth B, Kramer D, et al. Symptomatic Venous Thromboembolism After Adolescent Knee Arthroscopy. J Pediatr Orthop. 2019;39(3):125-129. doi:10.1097/BPO.0000000000000894
6. Allahabadi S, Faust M, Swarup I. Venous Thromboembolism After Pelvic Osteotomy in Adolescent Patients: A Database Study Characterizing Rates and Current Practices. J Pediatr Orthop. 2021;41(5):306-311. doi:10.1097/BPO.0000000000001798
7. Shore BJ, Hall M, Matheney TH, Snyder B, Trenor CC, Berry JG. Incidence of Pediatric Venous Thromboembolism After Elective Spine and Lower-Extremity Surgery in Children With Neuromuscular Complex Chronic Conditions: Do we Need Prophylaxis? J Pediatr Orthop. 2020;40(5):e375-e379. doi:10.1097/BPO.0000000000001483
8. Udén A. Thromboembolic complications following scoliosis surgery in Scandinavia. Acta Orthop Scand. 1979;50(2):175-178. doi:10.3109/17453677908989753
9. Kaabachi O, Alkaissi A, Koubaa W, Aloui N, Toumi NEH. Screening for deep venous thrombosis after idiopathic scoliosis surgery in children: a pilot study. Paediatr Anaesth. 2010;20(2):144-149. doi:10.1111/j.1460-9592.2009.03237.x
10. Erkilinc M, Clarke A, Poe-Kochert C, et al. Is There Value in Venous Thromboembolism Chemoprophylaxis After Pediatric Scoliosis Surgery? A 28-Year Single Center Study. J Pediatr Orthop. 2021;41(3):138-142. doi:10.1097/BPO.0000000000001746
11. Jain A, Karas DJ, Skolasky RL, Sponseller PD. Thromboembolic complications in children after spinal fusion surgery. Spine (Phila Pa 1976). 2014;39(16):1325-1329. doi:10.1097/BRS.0000000000000402
12. Greenwald LJ, Yost MT, Sponseller PD, Abdullah F, Ziegfeld SM, Ain MC. The role of clinically significant venous thromboembolism and thromboprophylaxis in pediatric patients with pelvic or femoral fractures. J Pediatr Orthop. 2012;32(4):357-361. doi:10.1097/BPO.0b013e31824b2a07
13. Murphy RF, Naqvi M, Miller PE, Feldman L, Shore BJ. Pediatric orthopaedic lower extremity trauma and venous thromboembolism. J Child Orthop. 2015;9(5):381-384. doi:10.1007/s11832-015-0697-1
14. Grandas OH, Klar M, Goldman MH, Filston HC. Deep venous thrombosis in the pediatric trauma population: an unusual event: report of three cases. Am Surg. 2000;66(3):273-276.
15. Vavilala MS, Nathens AB, Jurkovich GJ, Mackenzie E, Rivara FP. Risk factors for venous thromboembolism in pediatric trauma. J Trauma. 2002;52(5):922-927. doi:10.1097/00005373-200205000-00017
16. Sabharwal S, Passannante MR. Venous thromboembolism in children: preliminary results of a survey of POSNA members. J Pediatr Orthop. 2013;33(8):852-856. doi:10.1097/BPO.0b013e3182a35c7e
17. O’Brien SH, Candrilli SD. In the absence of a central venous catheter, risk of venous thromboembolism is low in critically injured children, adolescents, and young adults: evidence from the National Trauma Data Bank. Pediatr Crit Care Med. 2011;12(3):251-256. doi:10.1097/PCC.0b013e3181f36bd9
18. Meier KA, Clark E, Tarango C, Chima RS, Shaughnessy E. Venous thromboembolism in hospitalized adolescents: an approach to risk assessment and prophylaxis. Hosp Pediatr. 2015;5(1):44-51. doi:10.1542/hpeds.2014-0044
19. Mahajerin A, Branchford BR, Amankwah EK, et al. Hospital-associated venous thromboembolism in pediatrics: a systematic review and meta-analysis of risk factors and risk-assessment models. Haematologica. 2015;100(8):1045-1050. doi:10.3324/haematol.2015.123455
20. Wright JM, Watts RG. Venous thromboembolism in pediatric patients: epidemiologic data from a pediatric tertiary care center in Alabama. J Pediatr Hematol Oncol. 2011;33(4):261-264. doi:10.1097/MPH.0b013e3182134111
21. Morgan J, Checketts M, Arana A, et al. Prevention of perioperative venous thromboembolism in pediatric patients: Guidelines from the Association of Paediatric Anaesthetists of Great Britain and Ireland (APAGBI). Paediatr Anaesth. 2018;28(5):382-391. doi:10.1111/pan.13355
22. Andrew M, David M, Adams M, et al. Venous thromboembolic complications (VTE) in children: first analyses of the Canadian Registry of VTE. Blood. 1994;83(5):1251-1257.
23. Stokes S, Breheny P, Radulescu A, Radulescu VC. Impact of obesity on the risk of venous thromboembolism in an inpatient pediatric population. Pediatr Hematol Oncol. 2014;31(5):475-480. doi:10.3109/08880018.2014.886315
24. Stein PD, Beemath A, Olson RE. Obesity as a risk factor in venous thromboembolism. Am J Med. 2005;118(9):978-980. doi:10.1016/j.amjmed.2005.03.012
25. Crary SE, Buchanan GR, Drake CE, Journeycake JM. Venous thrombosis and thromboembolism in children with osteomyelitis. J Pediatr. 2006;149(4):537-541. doi:10.1016/j.jpeds.2006.06.067
26. Kim SJ, Sabharwal S. Risk factors for venous thromboembolism in hospitalized children and adolescents: a systemic review and pooled analysis. J Pediatr Orthop B. 2014;23(4):389-393. doi:10.1097/BPB.0000000000000053