**3.2 Diagnosis**

Pathophysiology and Clinical Aspects of 50 Venous Thromboembolism in Neonates, Renal Disease and Cancer Patients

While low molecular weight heparins, fondaparinux and direct thrombin inhibitors may offer alternatives to unfractionated heparin in patients with chronic kidney disease, more

Thromboembolism (TE) is still regarded as a rare event in childhood and therefore knowledge of diagnostics, therapy and prophylaxis is limited among general pediatricians. During the past years, however, it is increasingly recognized as having significant impact on mortality, chronic morbidity and the normal development of children, which has led to an enhanced sensitivity toward considering such events in respective patients. Besides the greater awareness, an objective increase in childhood thrombosis is due to the medical progress in the treatment of critically ill patients. This seemingly contradictory observation is easily explained by the increasing use of central catheters and innovative interventional procedures in the treatment of premature infants, neonates and older children who are critically ill, suffering from complex cardiac defects, and from malignant disease, respectively. Therapeutic and prophylactic measures have subsequently become increasingly important, but in addition to the complexity of the clinical background and the heterogeneity in the pattern of acquired and inherited risk factors for TE among patients, the physiological significant differences of the coagulation system between newborns, young children and adolescents and differences in drug metabolism do not allow general recommendations for therapeutic interventions like thrombolysis and prophylactic anticoagulation for the different clinical conditions. This situation is further complicated by

evidence are needed to determine the safe dose and monitoring strategy.

a lack of availability of pediatric formulations and pediatric data for new drugs.

The increasing knowledge of exogenous and endogenous thrombophilic risk factors has initiated a number of studies to assess the impact of such factors with respect to their contribution to the thrombophilic state, both individually but also in concert with other factors. In addition to their impact on a first thrombotic event, much of the interest is now focused on their importance for thrombotic relapses. Only such studies will give us an answer to questions concerning the indications for treatment, prophylaxis and its optimal duration. All management recommendations are reflecting the authors' experiences and opinions and are not based on evidence gained by controlled trials as such trials are either

The annual incidence of TE in childhood in general is considerably lower than in adults, with a reported frequency of 0.07 to 0.14 per 10.000 children or 5.3 per 10,000 referrals of children to the hospital. The results of a prospective German study suggested an incidence of 5.2 per 100,000 neonates, and a prospective Dutch study resulted in an estimate of 1.4 per 100,000 children and adolescents (Parasuraman & Goldhaber , 2006). More than 80% of TE in childhood were on a background of a severe preceding illness or other comparable predisposing factors. (Kuhle et al, 2004) Arterial TE in children is less common than venous thrombosis (Kuhle et al, 2004) with the exception of stroke. The estimated yearly incidence of stroke in childhood is between 3–8 per 100,000. (Giroud et al, 1995; Lynch et al, 2002). The highest incidence of 25–35 per 100,000 live births has been reported for neonates (Chalmer, 2005). In addition to its impact on the development of children, stroke also quantitatively

**3. Thrombosis in infants and children** 

completely lacking or still ongoing.

plays the most important role.

**3.1 Epidemiology** 
