The incidence of pediatric venous thromboembolic disease is increasing in hospitalized children. While the mainstay of treatment of pediatric thrombosis is anticoagulation, reports on the use of ...systemic thrombolysis, endovascular thrombolysis, and mechanical thrombectomy have steadily been increasing in this population. Thrombolysis is indicated in the setting of life- or limb-threatening thrombosis. Thrombolysis can rapidly improve venous patency thereby quickly ameliorating acute signs and symptoms of thrombosis and may improve long-term outcomes such as postthrombotic syndrome. Systemic and endovascular thrombolysis can result in an increase in minor bleeding in pediatric patients, compared with anticoagulation alone, and major bleeding events are a continued concern. Also, endovascular treatment is invasive and requires technical expertise by interventional radiology or vascular surgery, and such expertise may be lacking at many pediatric centers. The goal of this mini-review is to summarize the current state of knowledge of thrombolysis/thrombectomy techniques, benefits, and challenges in pediatric thrombosis.
Anemia is a common complication of severe forms of epidermolysis bullosa (EB). To date, there are no guidelines outlining best clinical practices to manage anemia in the EB population. The objective ...of this manuscript is to present the first consensus guidelines for the diagnosis and management of anemia in EB.
Due to the lack of high-quality evidence, a consensus methodology was followed. An initial survey exploring patient preferences, concerns and symptoms related to anemia was sent to EB patients and their family members. A second survey was distributed to EB experts and focused on screening, diagnosis, monitoring and management of anemia in the different types of EB. Information from these surveys was collated and used by the panel to generate 26 consensus statements. Consensus statements were sent to healthcare providers that care for EB patients through EB-Clinet. Statements that received more than 70% approval (completely agree/agree) were adopted.
The end result was a series of 6 recommendations which include 20 statements that will help guide management of anemia in EB patients. In patients with moderate to severe forms of EB, the minimum desirable level of Hb is 100 g/L. Treatment should be individualized. Dietary measures should be offered as part of management of anemia in all EB patients, oral iron supplementation should be used for mild anemia; while iron infusion is reserved for moderate to severe anemia, if Hb levels of > 80-100 g/L (8-10 g/dL) and symptomatic; and transfusion should be administered if Hb is < 80 g/L (8 g/dL) in adults and < 60 g/L (6 g/dL) in children.
In the antiphospholipid syndrome (APS), patients produce antiphospholipid antibodies (aPL) that promote thrombosis and adverse pregnancy outcomes. Current therapy with anticoagulation is only ...partially effective and associated with multiple complications. We previously discovered that aPL recognition of cell surface β2-glycoprotein I (β2-GPI) initiates apolipoprotein E receptor 2 (apoER2)-dependent signaling in endothelial cells and in placental trophoblasts that ultimately promotes thrombosis and fetal loss, respectively. Here we sought to identify a monoclonal antibody (mAb) to β2-GPI that negates aPL-induced processes in cell culture and APS disease endpoints in mice. In a screen measuring endothelial NO synthase (eNOS) activity in cultured endothelial cells, we found that whereas aPL inhibit eNOS, the mAb 1N11 does not, and instead 1N11 prevents aPL action. Coimmunoprecipitation studies revealed that 1N11 decreases pathogenic antibody binding to β2-GPI, and it blocks aPL-induced complex formation between β2-GPI and apoER2. 1N11 also prevents aPL antagonism of endothelial cell migration, and in mice it reverses the impairment in reendothelialization caused by aPL, which underlies the non-thrombotic vascular occlusion provoked by disease-causing antibodies. In addition, aPL inhibition of trophoblast proliferation and migration is negated by 1N11, and the more than 6-fold increase in fetal resorption caused by aPL in pregnant mice is prevented by 1N11. Furthermore, the promotion of thrombosis by aPL is negated by 1N11. Thus, 1N11 has been identified as an mAb that attenuates APS-related pregnancy complications and thrombosis in mice. 1N11 may provide an efficacious, mechanism-based therapy to combat the often devastating conditions suffered by APS patients.
To evaluate technical feasibility, complications, and clinical outcomes of endovascular thrombolysis for iliofemoral thrombosis at two tertiary-care children's hospitals.
Institutional review ...board-approved retrospective review from March 2003 through June 2013 showed that venous thrombolysis for iliofemoral thrombosis was performed in 57 children (64 limbs) with a median age of 16.1 years (mean age, 14.5 y; range, 1.0-17.8 y). Techniques included catheter-directed thrombolysis (CDT), percutaneous mechanical thrombectomy (PMT), and pharmacomechanical catheter-directed thrombolysis (PCDT) with adjunctive angioplasty and/or stent placement. Villalta and modified Villalta scales were applied retrospectively to follow-up data to assess postthrombotic syndrome (PTS).
Technical success (≥ 50% thrombolysis) rate was 93.7%: grade III (100%) in 19 limbs, grade II (50%-99%) in 41 limbs, and grade I (< 50%) in four limbs. Techniques included CDT with PCDT (32.8%) or PMT (35.9%), CDT alone (26.6%), PCDT alone (4.7%) or with adjunctive angioplasty (54.7%), and stent placement (6.3%). Mean duration of CDT was 36.5 hours (range, 2.9-89.6 h). There was one major complication (1.8%) of bleeding requiring transfusion. Minor complications (ie, bleeding) occurred in seven patients (12.2%). Median follow-up was 1.5 years (range, 30 d to 7 y). Seven patients underwent repeat thrombolysis for recurrent thrombosis. The PTS rate was 59.3% per modified Villalta scale but only 2.1% per Villalta scale.
Endovascular thrombolysis is technically feasible and safe for iliofemoral thrombosis in children. Variable results were seen with two scales to assess PTS, suggesting an acute need for standardization of outcome measurement in children.
To evaluate the technical feasibility and safety of percutaneous endovascular thrombolysis for extremity deep venous thrombosis (DVT) in children < 24 months old.
A retrospective chart review of a ...clinical and imaging database was performed for pediatric patients who underwent endovascular therapy for DVT between January 2010 and July 2013. Indications, techniques, technical and clinical success, and complications were reviewed. Techniques for thrombolysis included catheter-directed therapy (CDT) using alteplase infusion via a multi-side hole catheter, mechanical thrombectomy, and angioplasty. Short-term outcomes were assessed using surgical and imaging follow-up examinations for patency of the targeted vessel. Patients included 11 children (mean age, 9 mo; range, 3 wk-23 mo) who consecutively underwent endovascular thrombolysis for upper extremity (n = 6) or lower extremity (n = 5) DVT. The most common indication was preservation of venous access for future cardiac surgery or medical therapy.
The most common risk factor was the presence of a central venous catheter (10 of 11 patients). All patients with upper extremity DVT had congenital heart disease. CDT and angioplasty were performed in all patients. Venous patency was established in all patients. A grade III (95%-100%) thrombolysis response was achieved in seven patients, and a grade II (50%-95%) thrombolysis response was achieved in four patients. A major complication of pulmonary embolism occurred in one patient with upper extremity thrombolysis and was managed by intravenous systemic alteplase and heparin. No recurrence of thrombosis was found on average follow-up of 11.8 months (range, 1-41 mo).
Percutaneous endovascular thrombolysis for extremity DVT is safe and technically feasible in children < 24 months old.
Von Willebrand Disease (VWD) is the most common inherited bleeding disorder. VWD is characterized by an abnormal quantity or quality of von Willebrand Factor (VWF). Anemia is often found at ...presentation for a bleeding disorder evaluation due to chronic blood loss.
We hypothesized that anemia is associated with elevations in both VWF and factor VIII (FVIII) over baseline. We also hypothesized that obesity would be associated with increased levels of VWF.
We conducted a single-center review of the electronic health record for patients that had proximal von Willebrand profiles and Hb data.
We identified 4552 unique subjects with VWF studies and a CBC within 24 h. We found that decreasing hemoglobin inversely correlated with VWF antigen, VWF ristocetin cofactor activity, and FVIII activity. We also found that obesity and Black race were independently associated with increased VWF antigen, activity, and FVIII activity. Hb, race, and body mass index (BMI) continued to be determinants of VWF and FVIII levels in multivariable analysis.
Our study demonstrates that anemia, race, and BMI were found to be associated with elevation of VWF antigen, VWF activity, and FVIII levels. As many individuals with anemia present for evaluation for a bleeding disorder, these variables need to be considered.
- Anemia was found to be associated with elevation of VWF antigen, VWF activity and FVIII levels.
- Testing von Willebrand factor at times of anemia may mask a diagnosis of von Willebrand Disease.
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•Anemia associated with elevation of VWF levels•Testing at the time of an illness may lead to an elevation in VWF levels•Optimal timing for VWD testing upon resolution of anemia and acute illness status
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