Thrombotic Disorders in Children

Epidemiology

Studies have confirmed a significant increase in the diagnosis of venous thromboembolism (VTE) in pediatric tertiary hospitals across the United States. Although the overall incidence of thrombosis in the general pediatric population is quite low (0.07/100,000), the rate of VTE in hospitalized children is 60/10,000 admissions. Infants less than 1 yr old account for the largest proportion of pediatric VTEs, with a 2nd peak during adolescence.

The majority of children who develop a TE have multiple risk factors that may be acquired, inherited, and/or anatomic (Table 473-1). The presence of a central venous catheter (CVC) is the single most important risk factor for venous thromboembolism (VTE) in pediatric patients, associated with approximately 90% of neonatal VTE and 60% of childhood VTE. These catheters are often necessary for the care of premature neonates and children with acute and chronic diseases and are used for intravenous hyperalimentation, chemotherapy, dialysis, antibiotics, or supportive therapy. CVCs may damage the endothelial lining and/or cause blood flow disruption, increasing the risk of thrombosis. There are multiple other acquired risk factors that are associated with thrombosis, including trauma, infection, chronic medical illnesses, and medications. Cancer, congenital heart disease, and prematurity are the most common medical conditions associated with TEs.

Antiphospholipid antibody syndrome (APS) is a well-described syndrome in adults characterized by recurrent fetal loss and/or thrombosis. Antiphospholipid antibodies (APA) are associated with both venous and arterial thrombosis. The mechanism by which these antibodies cause thrombosis is not well understood. A diagnosis of APS requires the presence of both clinical and laboratory abnormalities (see under Laboratory Testing). The laboratory abnormalities must be persistent for 12 wk. Because of the high risk of recurrence, patients with APS often require long-term anticoagulation. It is important to note that healthy children may have a transient lupus anticoagulant, often diagnosed because of a prolonged PTT on routine preoperative testing. These antibodies may be associated with a recent viral infection and are not a risk factor for thrombosis.

Anatomic abnormalities that impede blood flow also predispose patients to thrombosis at an earlier age. Atresia of the inferior vena cava has been described in association with acute and chronic lower extremity deep venous thrombosis (DVT). May-Thurner syndrome (compression of the left iliac vein by the overlying right iliac artery) should be considered in patients who present spontaneously with left iliofemoral thrombosis, and thoracic outlet obstruction (Paget-Schroetter syndrome) frequently presents with effort-related axillary-subclavian vein thrombosis.

Clinical Manifestations

Extremity deep vein thrombosis (DVT): Children with acute DVT often present with extremity pain, swelling, and discoloration. A history of a current or recent CVC in that extremity should be very suggestive. Many times, symptoms of CVC-associated thrombosis are more subtle and chronic, including repeated CVC occlusion or sepsis, or prominent venous collaterals on the chest, face, and neck.

Pulmonary embolism (PE): Symptoms of PE include shortness of breath, pleuritic chest pain, cough, hemoptysis, fever, and, in the case of massive PE, hypotension and right heart failure. Based on autopsy studies, PEs are often not diagnosed, perhaps because young children are unable to accurately describe their symptoms and their respiratory deterioration may be masked by other conditions (Chapter 401.1).

Cerebral sinovenous thrombosis (CSVT): Symptoms may be subtle and may develop over many hours or days. Neonates often present with seizures, whereas older children often complain of headache, vomiting, seizures, and focal signs. They may also have papilledema and abducens palsy. Some patients may have a concurrent sinusitis or mastoiditis that has contributed to the thrombosis.

Renal vein thrombosis: Renal vein thrombosis is the most common spontaneous TE in neonates. Affected infants may present with hematuria, an abdominal mass, and/or thrombocytopenia. Infants of diabetic mothers are at increased risk, although the mechanism for this increased risk is unknown. Approximately 25% of cases are bilateral.

Peripheral arterial thrombosis: With the exception of stroke, the majority of arterial TEs in children are secondary to catheters, often in neonates related to umbilical artery lines or in patients with cardiac defects undergoing cardiac catheterization. Patients with an arterial thrombosis affecting blood flow to an extremity will present with a cold, pale, blue extremity with poor or absent pulses.

Stroke: Ischemic stroke commonly presents with hemiparesis, loss of consciousness, or seizures. This condition may occur secondary to pathology that affects the intracranial arteries (i.e., sickle cell disease, vasculopathy, or traumatic arterial dissection) or may be due to venous thrombi that embolize to the arterial circulation (placental thrombi, children with congenital heart disease or patent foramen ovale).

Diagnosis

Ultrasound with Doppler flow is the most commonly employed imaging study due for the diagnosis of upper or more often lower extremity VTE. Spiral CT is used most frequently for the diagnosis of PE (Fig. 473-1