Venous Thromboembolism in Children
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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2012, Journal of Emergency MedicineCitation Excerpt :Heritable thrombophilias such as factor V Leiden mutation, hyperhomocysteinemia, prothrombin G20210A mutation, elevated levels of lipoprotein A, and deficiencies in Proteins C and S have all been linked to thromboembolic disease in children (5,27). Thrombophilia may also be acquired, such as with increased factor VIII activity during significant infection and inflammatory states, anticoagulant deficiencies resulting from consumption in bacterial sepsis and disseminated intravascular coagulation, or production of inhibitory antibodies in acute viral infection, nephrotic syndrome, and antiphospholipid antibody syndrome (27,28). Knowledge of thrombophilias has two implications for the Emergency Physician:
Recognition and Management of Pediatric Venous Thromboembolism in the Emergency Department
2011, Clinical Pediatric Emergency MedicineCitation Excerpt :All heparins enhance the activity of antithrombin, an intrinsic anticoagulation protein produced by the liver. Although new evidence suggests that enoxaparin dosing is age related throughout childhood and the patient's dose will eventually be titrated based on anti-Xa levels, an appropriate and easy-to-remember starting dose to use in the ED setting is 1 mg/kg for all patients older than 2 months and 1.5 mg/kg for infants younger than 2 months7,14 Given its rapid half-life, unfractionated heparin should be used for acute VTE management in patients with a high risk of bleeding, those with critical or labile clinical status, and those with significant impairment of renal function, given the relatively greater renal elimination of LMWH.15 The use of thrombolysis is receiving increasing attention in the pediatric hematology community, with tissue plasminogen activator as the agent of choice in pediatric patients.