Antithrombotic Therapy in Children: Inherited Prothrombotic Conditions

Antithrombotic Therapy in Children: Inherited Prothrombotic ConditionsPatency of CVL is frequently maintained by intermittent boluses of heparin (200 to 300 U) daily, weekly, or monthly. For infants weighing <10 kg, a lower dose of 10 U/kg is frequently used to avoid transient anticoagulation of the infant. There is only one small, level II study assessing the need for prophylactic heparin. The study was conducted in children with cancer using echocardiography of the heart as the outcome measure, not venography. Although the study reported no benefit from flushing CVLs with heparin, the design and outcome measure limits the generalizability of this study. Local instillation of UK is the most commonly used therapy for treating a malfunctioning line that is “blocked” (Table 9). Based on several level V studies, patency is restored in approximately 80% of patients.
Inherited Prothrombotic Conditions: Inherited thrombophilia is usually defined by the following features: (1) positive family history; (2) early age of onset; (3) recurrent disease; and (4) multiple or unusual locations. Over half these individuals have associated environmental risk factors such as surgery, pregnancy, trauma, etc., and half or more of the individuals fulfilling these criteria will have demonstrable abnormalities in the following four genes: AT, protein C (PC), protein S (PS), and activated protein C resistance/factor V Leiden (FV-R506Q). A large number of other candidate genes have been proposed as risk factors for inherited thrombophilia; most of these candidates, however, have not undergone careful segregation or population studies to define their pathogenic role fully birth control online. In fact, some of the seemingly obvious candidates, such as abnormalities in fibrinolysis, do not appear to confer heritable risk. These latter studies are however hampered by the low prevalence of most of these inherited abnormalities in the general population.
Our understanding of inherited thrombophilia has been revolutionized over the past 5 years by the description of a number of relatively high-prevalence genetic risk factors, including factor V Leiden, prothrombin G20210A (IIG20210A) polymorphism, and hyper-homocysteinemia (MTHFR-C677T). For example, in the general white population, these risk factors are present in 3 to 8% and 2 to 3%, respectively, for heterozygous FV-R506Q and IIG20210A, and in 12 to 15% for homozygous MTHR C677T. The prevalence of these risk factors varies with race. These prevalence figures contrast with the 0.4% and 0.1% prevalence observed for PC and AT deficiencies, respectively.