Thrombosis and Thrombophilia in Children with Intestinal Failure Syndromes.

Intestinal failure (IF) results from acquired or congenital loss of small bowel affecting absorption and digestion. The most common reason for this condition is prematurity combined with surgery to treat necrotizing enterocolitis. It is defined as <200 cm of intestines (small and large) or <100 cm of jejunum. Both situations can lead to malabsorption and the need for total parenteral nutrition (TPN). The average length of time children with IF require TPN is >48 months. However, some require it indefinitely due to failure of intestinal adaptation. These children require placement of multiple central venous catheters (CVC) to administer nutrition and fluids, and CVCs are complicated by infection and occlusion. Having IF and long term TPN can also lead to complications such as liver disease and vitamin deficiencies. The indications for intestinal transplant include impaired venous access, life-threatening sepsis or progressive liver disease with coagulopathy in a child who indefinitely requires TPN. Our center performed its first intestinal transplant in 2005. Since then, multiple children have been referred for transplant evaluation.

To determine prevalence of catheter-related thrombosis and thrombophilia in a population of children referred for intestinal transplant.

Retrospective review of children being evaluated for IT between 2005 and 2008. Evaluation included review of vascular imaging results, thrombophilia testing and response to treatment with anticoagulation medications.

Thirteen children were evaluated. Magnetic resonance venography revealed that 11/13 (85%) had evidence of catheter-related DVT, with 7 (56%) having more than one vessel involved. Results of prothrombotic evaluation are included in the table.

Five children were treated with long-term (>3 months) anticoagulation therapy (warfarin in 1 and enoxaparin in 4). Prior to initiation of anticoagulation, the mean number of lines inserted per child was 4, post treatment 1.2 (p= 0.001). Before anticoagulation mean number of catheter-related bacteremia episodes per child was 3.8, after treatment 5 (p=0.55).

Children with IF and chronic TPN use have very high rates of catheter-related DVT and loss of venous access. The most common thrombophilia associated with this population are persistently elevated FVIII activity and low levels of natural anticoagulant proteins. This is most likely a reflection of liver insufficiency and chronic inflammation of recurrent bacteremia.

Anticoagulant therapy appears to preserve venous access and reduce the need for CVC replacement. Though our study population is small, the results highlight the problem of acquired hypercoagulability in a subset of children who rely on long-term central venous access. Prospective studies are needed to determine if prophylactic anticoagulation initiated prior to loss of first or second catheter will benefit this growing population of children and possibly delay or even prevent the need for intestinal transplantation.

Journeycake:Baxter Healthcare: Honoraria, Membership on an entity's Board of Directors or advisory committees. Off Label Use: anticoagulation in children.