Factor VIII and Catheter-Related Thrombosis in Children
Objective: If we can identify critically ill children at high risk for central venous catheter-related thrombosis, then we could target them for pharmacologic thromboprophylaxis. We determined whether factor VIII activity or G value was associated with catheter-related thrombosis in critically ill children.
Design: Prospective cohort study.
Setting: Two tertiary academic centers.
Patients: We enrolled children younger than 18 years who were admitted to the PICU within 24 hours after insertion of a central venous catheter. We excluded children with a recently diagnosed thrombotic event or those anticipated to receive anticoagulation. Children with thrombosis diagnosed with surveillance ultrasonography on the day of enrollment were classified as having prevalent thrombosis. Those who developed catheter-related thrombosis thereafter were classified as having incident thrombosis.
Interventions: None.
Measurements and Main Results: We enrolled 85 children in the study. Once enrolled, we measured factor VIII activity with one-stage clotting assay and determined G value with thromboelastography. Of those enrolled, 25 had incident and 12 had prevalent thromboses. The odds ratio for incident thrombosis per SD increase in factor VIII activity was 1.98 (95% CI, 1.10–3.55). The area under the receiver operating characteristic curve was 0.66 (95% CI, 0.52–0.79). At factor VIII activity more than 100 IU/dL, which was the optimal threshold identified using Youden index, sensitivity and specificity were 92.0% and 41.3%, respectively. The association between factor VIII activity and incident thrombosis remained significant after adjusting for important clinical predictors of thrombosis (odds ratio, 1.93; 95% CI, 1.10–3.39). G value was associated with prevalent but not with incident thrombosis.
Conclusion: Factor VIII activity may be used to stratify critically ill children based on their risk for catheter-related thrombosis.
Deep venous thrombosis (DVT) is a significant problem in critically ill children. The most important risk factor for DVT is the presence of a central venous catheter (CVC). DVT develops in approximately 17.5% of critically ill children with CVC. The risk for CVC-related DVT is low within 24 hours after insertion of the CVC but significantly increases thereafter. Although routinely used in critically ill adults, pharmacologic thromboprophylaxis is not recommended in children with CVC due to paucity of studies to support this practice. It would be ideal to provide thromboprophylaxis only to critically ill children at high risk for CVC-related DVT. At present, we do not have any tests to identify these children.
CVC, specifically the nontunneled type, is usually inserted when children are critically ill and likely hypercoagulable. Coagulation factors, particularly factor VIII, increase during critical illness. Factor VIII activity more than 150 IU/dL is associated with 2.6- to 4.8-fold odds of developing DVT in adults. Overall clot strength (i.e., G value), as measured with thromboelastography (TEG), reflects platelet activity. G value more than 12.4 kdyn/cm is associated with 30-fold odds of developing DVT in adults admitted to the surgical ICU.
We hypothesized that factor VIII activity or G value, when measured soon after insertion of a nontunneled CVC, could be used to stratify critically ill children based on their risk for CVC-related DVT so that in the future, we may target those at high risk for thromboprophylaxis. To test this hypothesis, we determined whether either of these biomarkers was associated with a future or incident CVC-related DVT in critically ill children. Post hoc, we explored whether either of them was associated with a current or prevalent DVT to determine whether they could be used to screen critically ill children who would need further testing to diagnose DVT.
Abstract and Introduction
Abstract
Objective: If we can identify critically ill children at high risk for central venous catheter-related thrombosis, then we could target them for pharmacologic thromboprophylaxis. We determined whether factor VIII activity or G value was associated with catheter-related thrombosis in critically ill children.
Design: Prospective cohort study.
Setting: Two tertiary academic centers.
Patients: We enrolled children younger than 18 years who were admitted to the PICU within 24 hours after insertion of a central venous catheter. We excluded children with a recently diagnosed thrombotic event or those anticipated to receive anticoagulation. Children with thrombosis diagnosed with surveillance ultrasonography on the day of enrollment were classified as having prevalent thrombosis. Those who developed catheter-related thrombosis thereafter were classified as having incident thrombosis.
Interventions: None.
Measurements and Main Results: We enrolled 85 children in the study. Once enrolled, we measured factor VIII activity with one-stage clotting assay and determined G value with thromboelastography. Of those enrolled, 25 had incident and 12 had prevalent thromboses. The odds ratio for incident thrombosis per SD increase in factor VIII activity was 1.98 (95% CI, 1.10–3.55). The area under the receiver operating characteristic curve was 0.66 (95% CI, 0.52–0.79). At factor VIII activity more than 100 IU/dL, which was the optimal threshold identified using Youden index, sensitivity and specificity were 92.0% and 41.3%, respectively. The association between factor VIII activity and incident thrombosis remained significant after adjusting for important clinical predictors of thrombosis (odds ratio, 1.93; 95% CI, 1.10–3.39). G value was associated with prevalent but not with incident thrombosis.
Conclusion: Factor VIII activity may be used to stratify critically ill children based on their risk for catheter-related thrombosis.
Introduction
Deep venous thrombosis (DVT) is a significant problem in critically ill children. The most important risk factor for DVT is the presence of a central venous catheter (CVC). DVT develops in approximately 17.5% of critically ill children with CVC. The risk for CVC-related DVT is low within 24 hours after insertion of the CVC but significantly increases thereafter. Although routinely used in critically ill adults, pharmacologic thromboprophylaxis is not recommended in children with CVC due to paucity of studies to support this practice. It would be ideal to provide thromboprophylaxis only to critically ill children at high risk for CVC-related DVT. At present, we do not have any tests to identify these children.
CVC, specifically the nontunneled type, is usually inserted when children are critically ill and likely hypercoagulable. Coagulation factors, particularly factor VIII, increase during critical illness. Factor VIII activity more than 150 IU/dL is associated with 2.6- to 4.8-fold odds of developing DVT in adults. Overall clot strength (i.e., G value), as measured with thromboelastography (TEG), reflects platelet activity. G value more than 12.4 kdyn/cm is associated with 30-fold odds of developing DVT in adults admitted to the surgical ICU.
We hypothesized that factor VIII activity or G value, when measured soon after insertion of a nontunneled CVC, could be used to stratify critically ill children based on their risk for CVC-related DVT so that in the future, we may target those at high risk for thromboprophylaxis. To test this hypothesis, we determined whether either of these biomarkers was associated with a future or incident CVC-related DVT in critically ill children. Post hoc, we explored whether either of them was associated with a current or prevalent DVT to determine whether they could be used to screen critically ill children who would need further testing to diagnose DVT.
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