Chapter 44: Thromboembolic Disease

High-Yield Facts

• The single greatest risk factor for thromboembolic disease in children is an indwelling central venous catheter.

• Disease patterns for pulmonary embolism in children and adolescents are similar to those in adults, yet diagnosis and management is often delayed or inappropriate.

• Arterial thromboembolism is more common in neonates and children with cardiac disorders, likely due to the use of umbilical artery catheters, cardiac catheters, ECMO circuits, and valvular disease.

• Anticoagulation is achieved acutely with unfractionated heparin (UH) or low-molecular-weight heparin (LMWH), followed by long-term anticoagulation with either LMWH or warfarin.

Thromboembolic events (TE) are increasingly recognized in children, with a 70% rise in diagnosis in tertiary children's hospitals since 2001.¹ There is a bimodal distribution, with neonates and adolescents at highest risk.^2–7 Arterial thromboembolism (ATE) is more common in neonates and children with cardiac disorders, likely due to the use of umbilical artery catheters, cardiac catheters, ECMO circuits, and valvular disease; however, it is also reported in older children and adolescents.^8,9 Arterial stroke is discussed further in Chapter 57.

Deep vein thrombosis (DVT) is the most common venous thromboembolism (VTE) with pulmonary embolism (PE) responsible for only 8% of pediatric VTE.⁴ Central venous sinus thrombosis (CVST) is a rare disease that is potentially fatal and leads to significant morbidity in survivors.^5–7

Arterial Thromboembolism [ATE]

ATE leads to higher morbidity and mortality than VTE.^10,11 About 9% to 22% of pediatric patients with ischemic stroke have no identifiable underlying risk factors.^12,13 Initial diagnosis is challenging, with median time to diagnosis of stroke taking over 24 hours in children and 88 hours in neonates, likely due to lack of initial consideration of the diagnosis.¹⁴ Among critically ill children, 96% of ATE is related to catheter usage.¹⁵ Noncatheter-related ATE occur in patients with underlying hematologic risk factors similar to those correlated with VTE and include organ transplantation and vasculitides such as Kawasaki disease and Takayasu arteritis.^16,17 Complications of ATE include death, stroke, limb loss, and dysfunction of the involved distal organs.

Deep Vein Thrombosis and Pulmonary Embolism

Risk Factors

Risk factors for developing VTE assume two primary forms: inherited and acquired. Inherited thrombophilias such as protein C and S deficiencies,¹⁸ antithrombin deficiency,¹⁹ and the presence of lupus anticoagulant²⁰ are considered high-risk states. Factor V Leiden disease, prothrombin mutation, elevated factor VIII, hyperhomocysteinemia, and others also add to the inherited risk.^21,22 Healthy children with a single thrombophilic trait rarely present with TE, but the risk increases with multiple traits or with the addition of acquired risk factors.^23,24 Congenital venous anomalies are also predisposing risk factors for DVT.^25,26

Acquired risk factors are ...