State-of-the-Art Pediatrics

Pediatric Thromboembolism Review

Co-Author: Shannon Carpenter, MD, MS, Division of Hematology-Oncology

Co-Author: Sara McElroy, MD, Fellow, Division of Hematology-Oncology

Column Editor: Amita Amonker, MD, FAAP | Pediatric Hospitalist | Assistant Professor of Pediatrics, UMKC School of Medicine 

Venous thromboembolism (VTE) is an increasingly diagnosed condition in the pediatric population that the general pediatrician should be aware of, particularly for hospitalized patients, who are at higher risk. In hospitalized patients, there is typically a provoking risk factor. The absence of a very clear etiology for an image-diagnosed thrombosis in a child should prompt the physician to do an evaluation to determine its cause. The evaluation is generally done in consultation with a pediatric hematologist. The presentation of thrombosis ranges from very distinct signs and symptoms to subtle findings. The mainstay of management is anticoagulation, which is managed by the pediatric hematologist, who is typically an expert in pediatric coagulation medicine.

Epidemiology

Although the incidence of thrombosis in children in the general population is low, in hospitalized children it is much higher and has been increasing over time from approximately 30 per 10,000 hospital admissions to 58 per 10,000 hospital admissions over a six-year span.^1,2 Within pediatrics, the incidence is highest among the neonatal and adolescent age groups.²

Risk Factors

There are many risk factors for VTE in children, the most common being the presence of a central venous catheter (CVC). A study using the Children’s Hospital-Acquired Thrombosis (CHAT) registry identified that 80% of thromboses in children were in the presence of a CVC.³ Other commonly occurring risk factors include trauma, surgical procedures, prolonged immobilization, and critical illness. In the setting of an unprovoked thrombus, a thrombus in an atypical location, multiple thromboses, or a patient with a strong family history of clots, it is important to consider the possibility of a hereditary thrombophilia. There are several known genetic thrombophilia conditions, with the most common being Factor V Leiden gene mutation, prothrombin gene mutation or deficiencies of antithrombin, proteins C or S.⁴

Clinical Presentation

The presentation of a thrombus in children is variable and depends on the age of the patient and the location of the clot. A clot in an extremity can present with swelling, pain and erythema. A clot associated with a central line can present with subtle findings of malfunction of the line. Some clots are asymptomatic and found incidentally when imaging for another reason. However, some clots will be life- or limb-threatening such as a pulmonary embolism, presenting with shortness of breath and chest pain, or a stroke, presenting with headache and/or focal neurologic deficits and, particularly, weakness.⁵

Management and Treatment

The mainstay of treatment for a deep venous thrombosis in a child is anticoagulation. Prior to determining the length of anticoagulation, it is important to assess whether the clot was provoked or unprovoked. Duration of treatment also depends on resolution of the clot, determined by imaging. In the setting of a provoked thrombus, the length of treatment is typically six weeks to three months; whereas, for an unprovoked clot, treatment could last six months to a year. A patient with an unprovoked clot should also undergo evaluation for an inherited thrombophilia; the evaluation should include genetic and lab testing. Historically, a stable patient would receive subcutaneous administration of low-molecular-weight heparin for anticoagulation; however, recent clinical trials have shown that direct oral anticoagulants such as rivaroxaban and apixaban are appropriate to treat a thrombus in pediatrics.⁶ These anticoagulants are often preferred as they don’t require an injection or lab monitoring. A patient who is unstable may require initial treatment with an intravenous anticoagulant with a plan to transition eventually to an oral or subcutaneous medication. Any patient with a thrombus requires follow-up with a pediatric hematologist.^7,8

References:

1. Raffini L, Huang YS, Witmer C, Feudtner C. Dramatic increase in venous thromboembolism in children’s hospitals in the United States from 2001 to 2007. Pediatrics. 2009;124(4):1001-1008. doi:10.1542/peds.2009-0768
2. Takemoto CM, Sohi S, Desai K, et al. Hospital-associated venous thromboembolism in children: incidence and clinical characteristics. J Pediatr. 2014;164(2):332-338. doi:10.1016/j.jpeds.2013.10.025
3. Jaffray J, Mahajerin A, Young G, et al. A multi-institutional registry of pediatric hospital-acquired thrombosis cases: The Children’s Hospital-Acquired Thrombosis (CHAT) project. Thromb Res. 2018;161:67-72. doi:10.1016/j.thromres.2017.11.019
4. Shoag J, Davis JA, Corrales-Medina FF. Venous thromboembolism in pediatrics. Pediatr Rev. 2021;42(2):78-89. doi:10.1542/pir.2019-0026
5. Jaffray J, Young G. Deep vein thrombosis in pediatric patients. Pediatr Blood Cancer. 2018;65(3):10.1002/pbc.26881. doi:10.1002/pbc.26881
6. Young G, Lensing AWA, Monagle P, et al. Rivaroxaban for treatment of pediatric venous thromboembolism: an Einstein-Jr phase 3 dose-exposure-response evaluation. J Thromb Haemost. 2020;18(7):1672-1685. doi:10.1111/jth.14813
7. Monagle P, Chan AKC, Goldenberg NA, et al. Antithrombotic therapy in neonates and children: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines [published correction appears in Chest. 2014 Dec;146(6):1694. Dosage error in article text] [published correction appears in Chest. 2014 Nov;146(5):1422]. Chest. 2012;141(2 suppl):e737S-e801S. doi:10.1378/chest.11-2308
8. Monagle P, Cuello CA, Augustine C, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: treatment of pediatric venous thromboembolism. Blood Adv. 2018;2(22):3292-3316. doi:10.1182/bloodadvances.2018024786