**3.3.2.1 Central venous catheters**

CVCs have become critically important as medical and supportive management of various diseases and have greatly improved quality of life. They bear two serious complications: thrombotic occlusion and CVC-associated DVT as well as systemic infections. CVCs seem to be the most important risk factor for DVT. The range of reported CVC-related DVT ranges from 1% to nearly 70%, reflecting the problem of different definitions, diagnostic methods and alertness.(Mitchell et al, 2003; Male et al, 2003) However, the estimated contribution of CVCs to all thromboembolic events in newborns is as high as 90% and over 50% in older children.(Parasuraman & Goldhaber, 2006) There are only a few controlled studies on the prevalence of CVC-related DVT and infection rate as well as the efficacy of antithrombotic measures to prevent catheter occlusion and infection.

#### **3.3.2.2 Childhood cancer**

TE is a well known complication in adult patients with cancer. With the exception of acute lymphoblastic leukemia (ALL), the knowledge about TE in childhood cancer is still limited. ALL has the highest rate of TE in childhood that is not necessarily related to the use of a CVC. In contrast, brain tumors have a rather low incidence of thrombosis with or without CVC.(Tabori et al, 2006) An overall estimation looks at a risk of up to 16%.

Venous Thromboembolism in Neonates, Children and

**3.3.2.5 Other acquired prothrombotic conditions** 

events may occur.

risk factors.

**3.4 Therapy and prophylaxis** 

initial treatment dose

initial prophylactic dose

after injection

**Recommendations** 

LMWH (Grade 1B).

\* 1 mg Enoxaparin = 110 anti-FXa units

Patients with Chronic Renal Disease – Special Considerations 57

heparin (UFH) for venous thrombosis. HIT-associated TE is mainly venous but arterial

Perinatal asphyxia, systemic infections/sepsis/DIC, congenital heart disease (CHD) and hypovolemia are the main risk factors in neonates, the latter particularly prone to arterial events in association with CHD and/or arterial catheters frequentlyused in an intensive care setting.47 There are additional factors in older children: trauma, major surgery, immobilization, estrogen containing contraceptives in adolescent girls, corticosteroid therapy, nephrotic syndrome, hemolytic uremic syndrome, inflammatory bowel disease, and rheumatic and other chronic disorders. To date, it remains an individual decision if and which antithrombotic prophylaxis should be offered considering additional and individual

Irrespective of an underlying disease, every thromboembolic manifestation should be treated, aiming at the complete recanalization of the occluded vessel and stopping the thrombotic process. In the vast majority of cases thrombosis will resolve under heparin given for 5–14 days. Other therapy options with a higher risk such as thrombolytic therapy or surgical embolectomy should be limited for patients with extensive thrombosis and/or threatened organ function. As LMWH show considerable advantages over UFH for therapeutic as well as prophylactic purposes, the following recommendations are in favor of LMWH. Yet evidence shows no difference in the antithrombotic efficacy. For detailed

**UFH i.v. Neonates < 5kg Children > 5kg Target aPTT at 4h** 

**LMWH s.c. Neonates < 5kg Children > 5kg Target anti-FXa at 4 h** 

For UFH: aPTT 4 hours after loading dose and 4 hours after each dosage adjustment, at least once daily; keep AT level within normal range; daily blood count (platelets!). For LMWH: anti-FX activity 4 hours

In children with thrombosis, we recommend anticoagulant therapy with either UFH or

maintenance 25–30 U/kg/h 20 U/kg/h 60–85 sec.

Enoxaparin\* 1 x 2.0 mg/kg/d 1 x 1.5 mg/kg/d 0.4–0.8 U/mL Dalteparin 1 x 200 U/kg/d 1 x 150 U/kg/d 0.4–0.8 U/mL Reviparin 2 x 150 U/kg/d 2 x 100 U/kg/d 0.5–1.0 U/mL

Enoxaparin\* 1 x 1.5 mg/kg/d 1 x 1.0 mg/kg/d < 0.4 U/mL Dalteparin 1 x 100 U/kg/d 1 x 50 U/kg/d < 0.4 U/mL Reviparin 2 x 50 U/kg/d 2 x 30 U/kg/d < 0.5 U/mL

Table 4. Recommended dosing of UFH and LMWH in neonates and children.

In children with VTE (CVL and non-CVL related): first TE for children:

recommendations refer to **Table 4** and reference (Monagle et al, 2004).

loading dose 1 x 75 U/kg/10 min 1 x 75 U/kg/10 min

TE in cancer is the result of complex interactions of a variety of factors such as the malignancy itself, chemotherapy and its side effects including infections or dehydration, CVCs, the unbalanced hemostatic system with predominant hypercoagulability as well as possible hereditary thrombophilia. The impact of the different types of childhood malignancy on the hemostatic system is still not well understood. Most reports are regarding ALL and show the highest risk for TE under ALL/non-Hodgkin lymphoma (NHL) treatment is during induction and re-induction therapy that contains L-asparaginase, the most common site being the upper deep venous system and the cerebral veins.
