Etiopathogenesis of pediatric thrombosis

IntroductionThrombosis is a relatively rare event during child-hood, affecting 0.7/100000 children, with the highestfrequency found in newborn infants and adolescents[1,2]. The etiology of thrombosis is influenced by age,neonate versus non-neonate, as well as site, arterialversus venous. Thrombosis during childhood is al-most always multifactorial, with both genetic andenvironmental factors important in the onset andprogression of thrombosis [3,4]. This paper willreview the etiology and pathogenesis of thrombosisin pediatric patients.Infants and children beyond the neonatal periodThe majority of infants and children present withthrombosis while hospitalized for a significant under-lying medical condition. Idiopathic thrombosis is veryrare in childhood; most symptomatic children man-ifest two or more risk factors, as displayed on Table I.Venous thrombi beyond the neonatal periodVenous thrombosis is more common in children thanarterial occlusions. Inflammation related to infection,surgery, trauma, malignancy or connective tissuedisorders is present in most children with venousthrombosis [3,4]. Blood disorders contributing toendothelial damage and stasis including sickle cellanemia, polycythemia and leukemia are rare butimportant risk factors for thrombosis.Indwelling catheters are involved in approximately30 to 60% of cases of venous thrombosis [3,5].Catheter-related thrombi develop in children whorequire long-term support with venous access devicesfor chronic disorders such as cystic fibrosis, hemo-philia, sickle cell anemia or short gut syndrome.However, in the setting of intense inflammation,such as sepsis or trauma, short-term femoral cathetersplaced for resuscitation often result in venous occlu-sion.The term thrombophilia denotes a category ofblood conditions that are associated with an increasedpropensity to develop thrombi. Thrombophilia maybe genetic or acquired and both types are commonlydetermined in children with thrombosis [6,7]. Antith-rombin deficiency is associated with a number ofdisorders including nephrotic syndrome, protein los-ing enteropathy and chemotherapy with L-asparagi-nase. Protein C deficiency is acquired byconsumption during severe bacterial infections suchas meningococcal sepsis and meningitis. Auto-im-mune protein S deficiency has been described follow-ing viral infections such as varicella [8,9].Antiphospholipid antibodies (APA) include thelupus anticoagulant (LA), anticardiolipin antibodyand anti-b2GPI antibodies. In young children APAusually occur following infection and are transient.APA in adolescents more commonly are persistent. Bydefinition, detection of APA six weeks or morefollowing initial determination constitutes the APASyndrome (APAS). However following infections withorganisms such as varicella or streptococcus, APAhave been determined to resolve over several months,without apparent long-term risk of thrombus recur-rence [9]. APAS may be secondary to systemic lupuserythematosus or other collagen vascular disease.However APAS in pediatric patients is usually pri-mary, or idiopathic. Patients with APAS are at highrisk for recurrent thrombosis following discontinua-tion of anticoagulation and most must be treated withwarfarin for an indefinite time [10].