Recommendations from the 2018 ASH pediatric VTE guidelines that were not addressed in this 2024 revision
| Thrombectomy and IVC filters | |
| Recommendation 6: The ASH guideline panel suggests against using thrombectomy followed by anticoagulation, and rather use anticoagulation alone in pediatric patients with symptomatic DVT or PE (conditional recommendation based on very low certainty in the evidence about effects). | Remarks: The panel recognized that in certain cases, for example, with cardiovascular compromise secondary to the VTE, thrombectomy may be appropriate, but in the experience of the panel such cases were rare and not without risk. Anecdotal cases of catheter-directed thrombectomy could not be adequately assessed. |
| Recommendation 7: The ASH guideline panel suggests against using IVC filter, and rather use anticoagulation alone in pediatric patients with symptomatic DVT or PE (conditional recommendation based on very low certainty in the evidence about effects). | Remarks: The panel considered the benefits vs risks involved in IVC filter use and determined their use should be reserved for certain cases: for example, those patients with DVT and absolute contraindication to anticoagulation, or those children who failed adequate standard anticoagulation therapy in whom a filter might reduce embolic risk. IVC filters should be temporary and there should always be a clear plan for removal. When the absolute contraindication is resolved, restarting the anticoagulation and removal of the filter is appropriate. It is not feasible to place IVC filters in children with a weight of <10 kg. |
| AT replacement therapy | |
| Recommendation 8a: The ASH guideline panel suggests against using AT replacement therapy in addition to standard anticoagulation, and rather use standard anticoagulation alone in pediatric patients with DVT/CSVT/PE (conditional recommendation based on very low certainty in the evidence about effects). | Remarks: The use of AT replacement has increased dramatically in recent years in the management of VTE in children, although supportive published data are extremely limited. The most commonly used rationale is to facilitate attainment of therapeutic heparin activity. Most evidence is indirect, being in the prophylactic situation rather than treatment, and based on the prophylactic studies, there is little evidence of clinical benefit and perhaps evidence of clinical harm. |
| Recommendation 8b: The ASH guideline panel suggests using AT replacement therapy in addition to standard anticoagulation rather than standard anticoagulation alone in pediatric patients with DVT/CSVT/PE who have failed to respond clinically to standard anticoagulation treatment and in whom subsequent measurement of AT concentrations reveals low AT levels based on age-appropriate reference ranges (conditional recommendation based on very low certainty in the evidence about effects). | Remarks: Despite the overall recommendation against AT use, the panel considered several subgroups, and specific situations in which they agreed AT use might be justified. First, in children with documented inherited AT deficiency, in whom anticoagulation of VTE was not achieving clinical benefit. Other situations included children with low levels of AT compared with age-appropriate levels (as distinct from adult levels), acute lymphoblastic leukemia on induction using asparaginase, nephrotic syndrome, neonates, after liver transplant, and in children with disseminated intravascular coagulation and VTE. Usually, AT use would be commenced if there was continuous thrombus growth and/or failure of clinical response despite adequate anticoagulation. There was, however, no evidence to suggest improved outcomes in these patients. |
| CVAD-related thrombosis | |
| Recommendation 9: The ASH guideline panel suggests no removal rather than removal of a functioning CVAD, in pediatric patients with symptomatic CVAD-related thrombosis who continue to require venous access (conditional recommendation based on very low certainty in the evidence about effects). | Remarks: The panel placed a high value on avoiding the insertion of another CVAD in children who may have limited availability of access sites and considered the thrombogenic effect of placing another line and new endothelial injury. The panel considered that treatment of symptomatic CVAD-related thrombus with anticoagulation likely leads to minimal complications. |
| Recommendation 10: The ASH guideline panel recommends removal rather than no removal of a nonfunctioning or unneeded CVAD, in pediatric patients with symptomatic CVAD-related thrombosis (strong recommendation based on very low certainty in the evidence about effects). | Remarks: In situations in which ongoing care of the primary condition can be delivered adequately without central venous access, removal of the stimulus to the thrombosis is appropriate. An overriding principle is that any central access device should be removed as soon as feasible within the confines of the overall treatment of the child. The panel made a strong recommendation despite very low certainty in the evidence for benefits based on high evidence of harm or high cost. |
| Recommendation 12: The ASH guideline panel suggests either removal or no removal of a functioning CVAD in pediatric patients who have symptomatic CVAD-related thrombosis with worsening signs or symptoms despite anticoagulation and who continue to require venous access (conditional recommendation based on very low certainty in the evidence about effects). | Remarks: The panel considered the variability in value placed by families and clinicians on maintaining line access compared with potential risk of infection and further thrombus progression, which will vary for individual patients. If alternative venous access is readily available, then removal of CVAD in setting of worsening VTE symptoms despite anticoagulation is appropriate. However, in some children, venous access is paramount. |
| LMWH vs VKAs | |
| Recommendation 13: The ASH guideline panel suggests using either LMWH or VKAs in pediatric patients with symptomatic DVT or PE (conditional recommendation based on very low certainty in the evidence about effects). | Remarks: The decision should depend on (1) patient values and preferences; (2) health services resources; (3) infrastructure and support; and (4) underlying condition, comorbidities, and other medications. |
| Purpura fulminans due to homozygous protein C deficiency | |
| Recommendation 24: The ASH guideline panel suggests using protein C replacement rather than anticoagulation in pediatric patients with congenital purpura fulminans due to homozygous protein C deficiency (conditional recommendation based on very low certainty in the evidence about effects). | Remarks: The panel determined that the long-term effectiveness of protein C replacement was superior to that offered by anticoagulation and also did not have the adverse bleeding risk of anticoagulation. However, protein C is expensive, and cost may be prohibitive. |
| Recommendation 25: The ASH guideline panel suggests using anticoagulation plus protein C replacement rather than anticoagulation alone in pediatric patients with congenital purpura fulminans due to homozygote protein C deficiency (conditional recommendation based on very low certainty in the evidence about effects). | Remarks: This recommendation applies in an acute setting (acute episode of purpura fulminans) in which the intervention of protein C replacement plus anticoagulation is considered a better option than anticoagulation alone. For long-term treatment, when recommendation to fully supplement with protein C cannot be followed for pragmatic or cost reasons, then the use of combined protein C replacement and anticoagulation rather than anticoagulation alone may reduce the required intensity of anticoagulation and hence reduce the bleeding risk. |
| Recommendation 26: The ASH guideline panel suggests using either liver transplantation or no liver transplantation (anticoagulation or protein C replacement) in pediatric patients with congenital purpura fulminans due to homozygous protein C deficiency (conditional recommendation based on very low certainty in the evidence about effects). | Remarks: Liver transplantation is curative of protein C deficiency but has its own acute and chronic risks and burden of care. The panel agreed that long-term maintenance on protein C replacement becomes increasingly expensive and difficult as the child grows and that long-term anticoagulation at the intensity required has significant bleeding risks. Hence, the optimal therapy depends on the values and preferences of the family, as well as local health service factors. Given the historical outcomes for children with this severe condition, discussion of potential pathways of care should be determined early before progressive organ damage has been sustained. |
| Thrombectomy and IVC filters | |
| Recommendation 6: The ASH guideline panel suggests against using thrombectomy followed by anticoagulation, and rather use anticoagulation alone in pediatric patients with symptomatic DVT or PE (conditional recommendation based on very low certainty in the evidence about effects). | Remarks: The panel recognized that in certain cases, for example, with cardiovascular compromise secondary to the VTE, thrombectomy may be appropriate, but in the experience of the panel such cases were rare and not without risk. Anecdotal cases of catheter-directed thrombectomy could not be adequately assessed. |
| Recommendation 7: The ASH guideline panel suggests against using IVC filter, and rather use anticoagulation alone in pediatric patients with symptomatic DVT or PE (conditional recommendation based on very low certainty in the evidence about effects). | Remarks: The panel considered the benefits vs risks involved in IVC filter use and determined their use should be reserved for certain cases: for example, those patients with DVT and absolute contraindication to anticoagulation, or those children who failed adequate standard anticoagulation therapy in whom a filter might reduce embolic risk. IVC filters should be temporary and there should always be a clear plan for removal. When the absolute contraindication is resolved, restarting the anticoagulation and removal of the filter is appropriate. It is not feasible to place IVC filters in children with a weight of <10 kg. |
| AT replacement therapy | |
| Recommendation 8a: The ASH guideline panel suggests against using AT replacement therapy in addition to standard anticoagulation, and rather use standard anticoagulation alone in pediatric patients with DVT/CSVT/PE (conditional recommendation based on very low certainty in the evidence about effects). | Remarks: The use of AT replacement has increased dramatically in recent years in the management of VTE in children, although supportive published data are extremely limited. The most commonly used rationale is to facilitate attainment of therapeutic heparin activity. Most evidence is indirect, being in the prophylactic situation rather than treatment, and based on the prophylactic studies, there is little evidence of clinical benefit and perhaps evidence of clinical harm. |
| Recommendation 8b: The ASH guideline panel suggests using AT replacement therapy in addition to standard anticoagulation rather than standard anticoagulation alone in pediatric patients with DVT/CSVT/PE who have failed to respond clinically to standard anticoagulation treatment and in whom subsequent measurement of AT concentrations reveals low AT levels based on age-appropriate reference ranges (conditional recommendation based on very low certainty in the evidence about effects). | Remarks: Despite the overall recommendation against AT use, the panel considered several subgroups, and specific situations in which they agreed AT use might be justified. First, in children with documented inherited AT deficiency, in whom anticoagulation of VTE was not achieving clinical benefit. Other situations included children with low levels of AT compared with age-appropriate levels (as distinct from adult levels), acute lymphoblastic leukemia on induction using asparaginase, nephrotic syndrome, neonates, after liver transplant, and in children with disseminated intravascular coagulation and VTE. Usually, AT use would be commenced if there was continuous thrombus growth and/or failure of clinical response despite adequate anticoagulation. There was, however, no evidence to suggest improved outcomes in these patients. |
| CVAD-related thrombosis | |
| Recommendation 9: The ASH guideline panel suggests no removal rather than removal of a functioning CVAD, in pediatric patients with symptomatic CVAD-related thrombosis who continue to require venous access (conditional recommendation based on very low certainty in the evidence about effects). | Remarks: The panel placed a high value on avoiding the insertion of another CVAD in children who may have limited availability of access sites and considered the thrombogenic effect of placing another line and new endothelial injury. The panel considered that treatment of symptomatic CVAD-related thrombus with anticoagulation likely leads to minimal complications. |
| Recommendation 10: The ASH guideline panel recommends removal rather than no removal of a nonfunctioning or unneeded CVAD, in pediatric patients with symptomatic CVAD-related thrombosis (strong recommendation based on very low certainty in the evidence about effects). | Remarks: In situations in which ongoing care of the primary condition can be delivered adequately without central venous access, removal of the stimulus to the thrombosis is appropriate. An overriding principle is that any central access device should be removed as soon as feasible within the confines of the overall treatment of the child. The panel made a strong recommendation despite very low certainty in the evidence for benefits based on high evidence of harm or high cost. |
| Recommendation 12: The ASH guideline panel suggests either removal or no removal of a functioning CVAD in pediatric patients who have symptomatic CVAD-related thrombosis with worsening signs or symptoms despite anticoagulation and who continue to require venous access (conditional recommendation based on very low certainty in the evidence about effects). | Remarks: The panel considered the variability in value placed by families and clinicians on maintaining line access compared with potential risk of infection and further thrombus progression, which will vary for individual patients. If alternative venous access is readily available, then removal of CVAD in setting of worsening VTE symptoms despite anticoagulation is appropriate. However, in some children, venous access is paramount. |
| LMWH vs VKAs | |
| Recommendation 13: The ASH guideline panel suggests using either LMWH or VKAs in pediatric patients with symptomatic DVT or PE (conditional recommendation based on very low certainty in the evidence about effects). | Remarks: The decision should depend on (1) patient values and preferences; (2) health services resources; (3) infrastructure and support; and (4) underlying condition, comorbidities, and other medications. |
| Purpura fulminans due to homozygous protein C deficiency | |
| Recommendation 24: The ASH guideline panel suggests using protein C replacement rather than anticoagulation in pediatric patients with congenital purpura fulminans due to homozygous protein C deficiency (conditional recommendation based on very low certainty in the evidence about effects). | Remarks: The panel determined that the long-term effectiveness of protein C replacement was superior to that offered by anticoagulation and also did not have the adverse bleeding risk of anticoagulation. However, protein C is expensive, and cost may be prohibitive. |
| Recommendation 25: The ASH guideline panel suggests using anticoagulation plus protein C replacement rather than anticoagulation alone in pediatric patients with congenital purpura fulminans due to homozygote protein C deficiency (conditional recommendation based on very low certainty in the evidence about effects). | Remarks: This recommendation applies in an acute setting (acute episode of purpura fulminans) in which the intervention of protein C replacement plus anticoagulation is considered a better option than anticoagulation alone. For long-term treatment, when recommendation to fully supplement with protein C cannot be followed for pragmatic or cost reasons, then the use of combined protein C replacement and anticoagulation rather than anticoagulation alone may reduce the required intensity of anticoagulation and hence reduce the bleeding risk. |
| Recommendation 26: The ASH guideline panel suggests using either liver transplantation or no liver transplantation (anticoagulation or protein C replacement) in pediatric patients with congenital purpura fulminans due to homozygous protein C deficiency (conditional recommendation based on very low certainty in the evidence about effects). | Remarks: Liver transplantation is curative of protein C deficiency but has its own acute and chronic risks and burden of care. The panel agreed that long-term maintenance on protein C replacement becomes increasingly expensive and difficult as the child grows and that long-term anticoagulation at the intensity required has significant bleeding risks. Hence, the optimal therapy depends on the values and preferences of the family, as well as local health service factors. Given the historical outcomes for children with this severe condition, discussion of potential pathways of care should be determined early before progressive organ damage has been sustained. |
AT, antithrombin.