Venous Thromboembolism in Children

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With improved pediatric survival from serious underlying illnesses, greater use of invasive vascular procedures and devices, and a growing awareness that vascular events occur among the young, venous thromboembolism (VTE) increasingly is recognized as a critical pediatric concern. This review provides background on etiology and epidemiology in this disorder, followed by an in-depth discussion of approaches to the clinical characterization, diagnostic evaluation, and management of pediatric VTE. Prognostic indicators and long-term outcomes are considered, with emphasis on available evidence underlying current knowledge and key questions for further investigation.

Section snippets

Characterization

VTE is classified clinically by various relevant descriptors, including first episode versus recurrent, symptomatic versus asymptomatic, acute versus chronic (a distinction that can be difficult at times), veno-occlusive versus nonocclusive, and idiopathic versus risk associated. This last category includes clinical prothrombotic risk factors (eg, exogenous estrogen administration, indwelling central venous catheter, and reduced mobility) and blood-based thrombophilic conditions (eg, transient

Epidemiology

Several years ago, registry data revealed an estimated cumulative incidence of 0.07 per 10,000 (5.3 per 10,000 hospitalizations) for extremity deep venous thrombosis (DVT) or pulmonary embolism (PE) among non-neonatal Canadian children [1] and an incidence rate of 0.14 per 10,000 Dutch children per year for VTE in general [2]. More recently, an evaluation of the National Hospital Discharge Survey and census data for VTE in the United States disclosed an overall incidence rate of 0.49 per 10,000

Etiology

The pathogenesis of VTE readily can be appreciated by considering the Virchow triad, consisting of venous stasis, endothelial damage, and the hypercoagulable state. In children, greater than 90% of VTEs are risk associated [2], [4], [5] (compared with approximately 60% in adults), with risk factors often disclosed from more than one component of this triad. Specific examples of VTE risk factors in children are shown in Fig. 1. One of the most common clinical prothrombotic risk factors in

Clinical presentation

The degree of clinical suspicion for acute VTE in children should be influenced principally by (1) clinical prothrombotic risk factors and family history of early VTE or other vascular disease elicited on thorough interview; (2) known thrombophilia traits and risk factors; and (3) clinical signs and symptoms. The signs and symptoms of VTE depend on anatomic location and organ system affected and are influenced by characteristics of veno-occlusiveness and chronicity. The classic manifestation of

Radiologic imaging

Historically, venography has been the gold standard for diagnosis of venous thrombosis but limited by its invasiveness. In recent years, this modality has experienced a diminishing role with the development of effective noninvasive or minimally invasive radiologic imaging techniques. Radiologic imaging is used not only to confirm the clinical diagnosis of VTE but also to define the extent and occlusiveness of thrombosis. For suspected DVT of the distal or proximal lower extremity, compression

Treatment

A summary of conventional antithrombotic agents and corresponding target anticoagulant levels, based on recent pediatric recommendations [14], is provided in Table 3 for initial (ie, acute phase) and extended (ie, subacute phase) treatment. Conventional anticoagulants attenuate hypercoagulability, decreasing the risk for thrombus progression and embolism, and rely on intrinsic fibrinolytic mechanisms to dissolve the thrombus over time. The conventional anticoagulants used most commonly in

Outcomes

Complications of VTEs can occur acutely and over the long term. Short-term adverse outcomes include major hemorrhagic complications of antithrombotic interventions and of the thrombotic event itself (eg, post-thrombotic hemorrhage in the brain, testis, or adrenal gland); early recurrent VTE (including DVT and PE); SVC syndrome in DVT of the upper venous system; acute renal insufficiency in RVT; catheter-related sepsis, PE, and catheter malfunction (sometimes necessitating surgical replacement)

Future directions

VTE has emerged in recent years as a critical pediatric concern with acute and chronic sequelae. Important and highly clinically relevant questions on its etiology, pathogenesis, and natural history remain to be addressed via collaborative cohort studies. For example, what are the mechanisms by which distinct APA mediate the prothrombotic state and, in turn, confer distinct risks for relevant outcomes of thrombus progression, recurrence, and embolism? Do criteria for APA syndrome established in

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