Frederick Mun, Arjun Gupta, Manjeera Rednam, Ashok Johari, Amit Jain.

Response/Recommendation: Adolescence, central venous catheter (CVC) placement, obesity, trauma, and oral contraceptive use are the most commonly reported risk factors for venous thromboembolism (VTE) in pediatric patients undergoing orthopaedic surgery. Currently, there are no standardized tools that are well-developed enough to capture all these factors. Due to the low incidence of VTE in the pediatric population, VTE chemoprophylaxis should not be routinely used except in high-risk individuals who can be identified with the use of simple screening questions.

Strength of Recommendation: Moderate.

Rationale: Numerous studies have documented the increased risk for venous thromboembolism (VTE) in patients undergoing orthopaedic surgery. It has been widely reported that the incidence of VTE is lower among pediatric patients than adults^1-6. Existing literature documents various patient characteristics, comorbidities, and perioperative variables that can correlate with increased VTE risk among pediatric orthopaedic patients. Based on these studies, a number of screening tools and VTE risk assessment algorithms have been proposed to guide risk stratification and inform clinical decision-making regarding the utilization of thromboprophylaxis strategies^7-9. However, compared to existing VTE guidelines for adult patients, current information on pediatric patients has been poorly synthesized, with no clear consensus on the independent predictors of VTE risk. Previous studies have been limited by narrow clinical focus (e.g., lower extremity trauma patients only), too few VTE events for meaningful correlations, uncontrolled confounding variables, and conflicting findings with previously published reports. As a result, guidelines on VTE prophylaxis are reliant on seemingly discordant methods of risk stratification. We conducted a review of current literature on the risk factors for VTE among pediatric orthopaedic patients. This was done in an effort to gauge the reliability of recent studies, and to evaluate the most widely adopted risk stratification methods for this population.

Studies on the pediatric population consistently cite older age and adolescence as the most common risk factors for VTE^2-4,10-14. Jain et al.^11, reported that for each year of age, the incidence of VTE increased 1.37-fold (p < 0.01) among patients ≤ 18 years of age undergoing spinal fusion surgery. Samineni et al.¹³, found that the mean age of VTE amongst orthopaedic patients was 15.2 years, compared to 9.9 years for VTE amongst non-orthopaedic patients (p < 0.0001). Murphy et al,. and Guzman et al., reported that the mean ages of children who did and did not develop VTE were 16.9 years versus 15.1 years (p = 0.01) and 17 years vs. 12 years, respectively^10,18. Van Arendonk et al., subdivided their study population and found the following risk profiles for each age subgroup: 0 – 12 years (odds ratio [OR]: 1), 13 – 15 years (OR: 1.96, p < 0.001), 16 – 21 years (OR: 3.77, p < 0.001). Only one study in our review claimed that they did not find an association between age and VTE risk. However, the authors of that study were unable to identify any risk factors at all¹⁵. Overall, studies reported that increased age (generally past 12 years), increased the risk of VTE.

A frequently reported perioperative variable associated with increased risk of VTE is presence of a CVC or peripherally inserted central catheter (PICC)^{10,12,14,16,17}. Van Arendonk et al., found that the presence of a PICC increases the OR for the diagnosis of VTE to 1.33 (p < 0.001)¹⁴. More recently, Baker et al., suggested that the pathophysiology of this relationship may pertain to CVC-associated bloodstream infection (p < 0.001)¹⁶.

Another commonly cited patient comorbidity known to increase VTE risk is obesity or metabolic syndrome^2,3,10,14. Van Arendonk et al., reported an OR of 3.03 for VTE development among obese patients compared to patients with a normal body mass index (BMI) (p < 0.001)¹⁴. Prolonged hospital stay has also been associated with an increased risk of VTE. However, it maybe be challenging to infer causal relationships as patients may have other medical comorbidities or socioeconomic factors, that can affect this variable^2,10,14,16.

The restricted clinical focus of most articles we reviewed made it difficult to analyze the distribution of the different injury types among patients who develop VTE in this setting. Overall, we found that pediatric patients with multiple fractures, or those presenting with polytrauma, were more likely to be diagnosed with VTE during their orthopaedic care^2,4,10,14. Furthermore, the association between Injury Severity Score (ISS) and the diagnosis of VTE was further validated by Van Arendonk et al. They found a direct relationship between the two: mild injury, ISS < 9 (OR: 1, reference); moderate injury, ISS 9 – 15 (OR: 3.95, p < 0.001); severe injury, ISS 16 – 24 (OR: 5.94, p < 0.001); very severe injury, ISS 25 – 75 (OR: 7.19, p < 0.001). Additionally, they also found a similar relationship between VTE risk and a worsening Glasgow coma scale (GCS) score¹⁴.

There is also some evidence to suggest that patients with neuromuscular diseases or other syndromic conditions may be at increased risk for VTE^2,11. Jain et al., reported that among pediatric spine patients, children with idiopathic scoliosis demonstrated the lowest incidence of VTE after corrective spine surgery (OR: 1, reference). By comparison, children with congenital and syndromic scoliosis/kyphoscoliosis were at much higher risk (OR: 4.21, p = 0.04 and OR: 7.14, p < 0.01, respectively). In addition, children with thoracolumbar fractures who underwent spine surgery were found to have the highest incidence of VTE (OR: 12.59, p < 0.01)¹¹. Similarly, Georgopoulos et al., (2016) reported that neuromuscular and neurological disorders were significantly associated with VTE (p = 0.0042)².

A number of other factors associated with VTE were considered in this review. However, a consensus on these variables was based on limited information. Two studies suggested that a patient’s intubation status was associated with development of VTE in the pediatric orthopaedic population^14,16. Additionally, one study in our review reported on prolonged tourniquet time in adolescents undergoing knee arthroscopy³. Most evidence suggests that both males and females are vulnerable to VTE, and that a patient’s sex is not a significant predictor of VTE risk^3,11,14,15.

We found that a limited number of screening tools for VTE were specifically being used for pediatric orthopaedic patients^7-9,18. Risk factors commonly highlighted in the pediatric population include older age, obesity, CVC use, and a positive family or past individual history of VTE. Padhye et al., developed a screening tool that assigned one point for each of the following risk factors: age > 14 years, BMI > 30kg/m², limited or altered mobility > 48 hours, cardiovascular flow anomalies, metabolic syndromes, CVC use, prolonged surgery > 120 minutes, and repeat/complicated surgery. If patients had a score of 4 or more points, immediate referral to hematology is advised. Furthermore, patients should be under automatic consideration for both chemical and mechanical VTE prophylaxis⁹. In another study, Ellis et al., reported on the efficacy of a screening tool that categorized risk factors as high-risk (family or past medical history of VTE), major risk (oral contraceptives, CVC, and cancer), and minor risk (obesity and other various comorbidities). Utilizing the screening tool significantly increased sensitivity for identifying risk factors such as family history of blood clots (p < 0.001), history of previous blood clot (p = 0.059), recurrent miscarriages in the family (p = 0.010), and smoking exposure (p = 0.062)⁷. Both studies recommended the initiation of VTE prophylaxis depending on the number and/or severity of risk factors as determined by their screening tools^7,9.

A recent study by MacNevin et al., evaluated the efficacy of an existing perioperative VTE screening tool. Similar to the two previous screening tools, they classified patients by “risk levels” based on their “risk scores”: Level 1 low risk (risk score 0 to 2), Level 2 moderate risk (risk score 3), and Level 3 high risk (risk score > 4). Although specific risk factors were not reported in the study, they found a significant reduction (4.09% vs. 2.13%, p = 0.046) in the use of thromboprophylaxis in the surgical patient cohort after implementation of the screening tool. Moderate and high-risk patients were also more likely to be undergoing bony surgical procedures, scoliosis surgery and hip procedures⁸.

Finally, in a recent survey of members of the Pediatric Orthopaedic Society of North America (POSNA), respondents reported oral contraceptive pills (OCP) use (81.2%), family history of thrombosis (72.8%), and obesity (70.7%), as the top risk factors they used to guide implementation of VTE chemical and mechanical prophylaxis in their patients¹⁸. Trauma-related procedures (65%), spinal fusion (64%), and hip reconstruction (60%) had the highest frequency of VTE prophylaxis use, surgery on patients with a neuromuscular diagnosis had a considerably lower frequency (34%, p < 0.001)¹². Similarly, Van Arendonk et al., reported on an increased OR for VTE in trauma patients with a high ISS¹⁴.

In summary, older age, CVC placement, obesity, trauma, and OCP use are the most commonly reported risk factors for VTE in pediatric patients undergoing orthopaedic surgery. Currently, there are no standardized tools that are well-developed enough to capture all these factors. Due to the low incidence of VTE in the pediatric population, VTE chemoprophylaxis should not be routinely used except in high-risk individuals who can be identified with simple screening questions.

References:

1.         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.

2.         Georgopoulos G, Hotchkiss MS, McNair B, et al. Incidence of Deep Vein Thrombosis and Pulmonary Embolism in the Elective Pediatric Orthopaedic Patient. J Pediatr Orthop. 2016;36(1):101-109.

3.         Murphy RF, Heyworth B, Kramer D, et al. Symptomatic Venous Thromboembolism After Adolescent Knee Arthroscopy. J Pediatr Orthop. 2019;39(3):125-129.

4.         Murphy RF, Naqvi M, Miller PE, et al. Pediatric orthopaedic lower extremity trauma and venous thromboembolism. J Child Orthop. 2015;9(5):381-384.

5.         Sandoval JA, Sheehan MP, Stonerock CE, et al. Incidence, risk factors, and treatment patterns for deep venous thrombosis in hospitalized children: an increasing population at risk. J Vasc Surg. 2008;47(4):837-843.

6.         Victoria T, Mong A, Altes T, et al. Evaluation of pulmonary embolism in a pediatric population with high clinical suspicion. Pediatr Radiol. 2009;39(1):35-41.

7.         Ellis HB, Jr., Sabatino MJ, Clarke Z, et al. The Importance of a Standardized Screening Tool to Identify Thromboembolic Risk Factors in Pediatric Lower Extremity Arthroscopy Patients. J Am Acad Orthop Surg. 2019;27(9):335-343.

8.         MacNevin W, Padhye K, Alkhalife Y, et al. Optimizing pharmacologic thromboprophylaxis use in pediatric orthopedic surgical patients through implementation of a perioperative venous thromboembolism risk screening tool. Pediatric blood &amp; cancer. 2021;68(2):e28803.

9.         Padhye K, El-Hawary R, Price V, et al. Development of a perioperative venous thromboembolism prophylaxis algorithm for pediatric orthopedic surgical patients. Pediatr Hematol Oncol. 2020;37(2):109-118.

10.       Guzman D, Sabharwal S, Zhao C, et al. Venous thromboembolism among pediatric orthopedic trauma patients: a database analysis. J Pediatr Orthop B. 2018;27(2):93-98.

11.       Jain A, Karas DJ, Skolasky RL, et al. Thromboembolic complications in children after spinal fusion surgery. Spine (Phila Pa 1976). 2014;39(16):1325-1329.

12.       Sabharwal S, Zhao C, Passanante M. Venous thromboembolism in children: details of 46 cases based on a follow-up survey of POSNA members. J Pediatr Orthop. 2013;33(7):768-774.

13.       Samineni AV, Sanborn R, Shea J, et al. Pediatric Venous Thromboembolism: Different Rates of Incidence, Anatomic Locations, and Risk Factors Between Orthopaedic and Nonorthopaedic Related Patients. Journal of Pediatric Orthopaedics. 2021;41(6):379-384.

14.       Van Arendonk KJ, Schneider EB, Haider AH, et al. Venous Thromboembolism After Trauma: When Do Children Become Adults? JAMA Surgery. 2013;148(12):1123-1130.

15.       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.

16.       Baker D, Sherrod B, McGwin G, Jr., et al. 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.

17.       Shore BJ, Hall M, Matheney TH, et al. 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.

18.       Murphy RF, Williams D, Hogue GD, et al. Prophylaxis for Pediatric Venous Thromboembolism: Current Status and Changes Across Pediatric Orthopaedic Society of North America From 2011. J Am Acad Orthop Surg. 2020;28(9):388-394.