SARS‐CoV‐2 infection (coronavirus disease 2019 COVID‐19) induces a stark procoagulant state, with many hospitalized adults developing thrombosis despite prophylactic anticoagulation. This study aimed ...to characterize hemostatic parameters and associated clinical outcomes of COVID‐19, such as thrombosis and bleeding, in children and to assess thromboprophylaxis use. This multicenter observational cohort study included 79 patients aged up to 18 years admitted to all pediatric hospitals in Québec, Canada, with SARS‐CoV‐2 infection during a 5‐month period. D‐dimers were elevated in 18/19 patients (94.7%) and fibrinogen in 15/26 patients (60%). Eleven patients (13.9%) received anticoagulant thromboprophylaxis. One thrombotic event and one major bleed were observed.
Thromboembolism (TE) is associated with reduced survival in pediatric acute lymphoblastic leukemia (ALL). It has been hypothesized that TE might signal leukemic aggressiveness. The objective was to ...determine risk factors for TE during ALL induction (TEind) therapy and whether TEind is associated with treatment refractoriness. This retrospective cohort study using the population‐based Cancer in Young People Canada (CYP‐C) registry included children <15 years of age diagnosed with ALL (2000–2019) and treated at one of 12 Canadian pediatric centers outside of Ontario. Univariate and multivariable logistic regression models were used to determine risk factors for TEind and whether TEind predicted induction failure and ALL treatment intensification. The impact of TEind on overall and event‐free survival was estimated using Cox proportional hazard regression models. The study included 2589 children, of which 45 (1.7%) developed a TEind. Age (<1 year and ≥10 years vs. 1–<10 years), T‐cell phenotype, high‐risk ALL, and central nervous system involvement were all associated with TEind in univariate analysis. Age and T‐cell phenotype remained independent predictors of TEind in multivariable analysis. Induction failure occurred in 53 patients (2.1%). TEind was not associated with induction failure (OR: not estimable) or treatment intensification (adjusted OR 95% CI: 0.66 0.26–1.69). TEind was independently associated with overall survival (adjusted HR 95% CI: 2.54 1.20–5.03) but not event‐free survival (adjusted HR 95% CI 1.86 0.98–3.51). In this population‐based study of children treated with contemporary chemotherapy protocols, TEind was associated with age and T‐cell phenotype and mortality but did not predict induction failure.
There are conflicting data about whether the development of cancer‐associated thrombo‐embolism (TE) negatively impacts survival in children. The objective was to determine whether TE during treatment ...was associated with overall survival (OS) and event‐free survival (EFS) in children with acute lymphoblastic leukemia (ALL). We performed a population‐based retrospective cohort study using the Cancer in Young People‐Canada registry. Children <15 years of age were diagnosed with de novo ALL (2000–2016). The primary exposure variable was radiologically‐confirmed thrombo‐embolism requiring medical intervention. Multivariable Cox regression models were used to determine the impact of thrombo‐embolism on survival, where TE was time‐dependent. We included 2006 children (median age: 4 years, 88.5% precursor B‐cell ALL). Thrombo‐embolism occurred in 113 patients (5.6%), at a median time of 107 days (interquartile range: 35–184 days) after ALL diagnosis. Among standard/low‐risk patients, 41/1165 (3.5%) developed TE while among high/very high‐risk patients, 72/841 (8.6%) developed TE. Patients with TE had a significantly worse OS (adjusted HR aHR of death: 2.61, 95% CI: 1.62–4.22, p < 0.001) and EFS (aHR of an event death, relapse, second malignancy: 2.03, 95% CI: 1.35–3.05, p = 0.001), compared with patients without TE. No statistically significant difference was seen in standard/low risk ALL for OS and EFS, but TE was associated with a significantly lower OS and EFS in children with high/very high‐risk ALL (aHR of death: 2.90, 95% CI: 1.79–4.72, p < 0.001; aHR of an event: 2.02, 95% CI: 1.30–3.12, p = 0.002). Thus, TE led to a statistically significant reduction in OS and EFS in children with high risk/very high‐risk leukemia.
Introduction
Persons with inherited bleeding disorders are at a substantial risk of bleeding following dental procedures.
Aim
To compare the outcomes and use of haemostatic treatment pre‐ and ...post‐implementation of a standardized protocol for dental procedures at a Hemophilia Treatment Centre.
Methods
We conducted a retrospective cohort study of outpatient and inpatient dental procedures and maxillofacial surgeries sustained by people with bleeding disorders treated at a comprehensive Hemophilia Treatment Centre (2013‐2020), comparing patients’ outcomes before and after the introduction of the protocol in 2018. The protocol, built using a multidisciplinary approach, suggested haemostatic treatment based on the invasiveness of the dental procedure and the proposed anaesthesia. Our primary outcome was the rate of procedural bleeding leading to medical or dental reintervention within 10 days. Secondary outcomes included the use of systemic haemostatic treatment and treatment‐related adverse effects.
Results
Overall, 137 dental procedures in 95 patients (median age: 29 years; 78% males; 74% haemophilia, 14% von Willebrand disease, 12% other disorders) were included.
Seventeen procedural bleedings were reported (12.4%). Procedural bleeding occurred in 14.8% and 8.9% of patients in the control and intervention groups (p = .304). No major bleeding occurred. Tranexamic acid was used more consistently after protocol implementation (72.8% vs. 89.3%, p = .019), while factor concentrates use decreased (65.4% vs. 44.6%, p = .016), and desmopressin use remained constant (46.4% vs. 32.1%, p = .100). No treatment‐related adverse effects were reported.
Conclusion
The use of a standardized protocol increased the use of tranexamic acid, with a nonstatistically significant reduction in procedural bleeding rate.
Hemophilia in a Changing Treatment Landscape Pelland-Marcotte, Marie-Claude; Carcao, Manuel D
Hematology/oncology clinics of North America,
06/2019, Letnik:
33, Številka:
3
Journal Article
Recenzirano
The mainstay of hemophilia management has been the regular, prophylactic infusion of missing coagulation factors VIII/IX. This approach is limited by the need for frequent intravenous infusions, high ...cost, limited availability, and the development of inhibitory antibodies to factors VIII/IX. Numerous recent breakthroughs are addressing many of these limitations. These include the development of extended half-life factors that require less frequent infusions and the development of various novel agents that can be given subcutaneously and infrequently, including FVIII-mimetic antibody and downregulators of natural anticoagulants. Finally, gene therapy is set to offer patients a possibility for a cure.
Summary
Acquired von Willebrand syndrome (AVWS) is reported in high‐flow high‐shear congenital cardiac disorders. We hypothesized that the narrowed pulmonary vasculature in idiopathic pulmonary ...arterial hypertension (IPAH) may induce AVWS. We conducted a cross‐sectional evaluation of children with IPAH. Patients with bleeding symptoms and/or laboratory abnormalities (thrombocytopenia, anomalies in coagulation screening tests) were tested in‐depth for haemostatic defects. Fourteen children were followed with IPAH of which 8 were eligible. Four children exhibited abnormal bleeding scores (International Society on Thrombosis and Haemostasis Bleeding Assessment Tool: 3–5). All 8 patients showed very prolonged platelet function analyser (PFA)‐100 closure times. Six children demonstrated either mild thrombocytopenia or low‐normal von Willebrand factor (VWF) antigen (VWF:Ag) or VWF activity mean (range), in iu/dl: VWF:Ag: 70 (61–91); VWF activity: 57 (34–70). Average VWF collagen binding capacity (VWF:CB) was 64 iu/dl (range: 53–123 iu/dl), with low‐normal VWF activity/VWF:Ag or VWF:CB/VWF:Ag ratios occurring in five patients. All children had normal multimers distribution patterns. One patient underwent a lung transplantation, with normalization of haemostatic abnormalities post‐surgery. Overall, 8 out of 14 children with IPAH had mild to moderate bleeding symptoms and/or laboratory abnormalities in keeping with AVWS. Normalization of the haemostatic defects following lung transplantation and lack of family history of bleeding attests to the acquired nature of their defects.
Congenital erythropoietic porphyria (CEP), a rare form of porphyria, is caused by a defect in the heme biosynthesis pathway of the enzyme uroporphyrinogen III synthase (UROS). Uroporphyrinogen III ...synthase deficiency leads to an accumulation of nonphysiological porphyrins in bone marrow, red blood cells, skin, bones, teeth, and spleen. Consequently, the exposure to sunlight causes severe photosensitivity, long-term intravascular hemolysis, and eventually, irreversible mutilating deformities. Several supportive therapies such as strict sun avoidance, physical sunblocks, red blood cells transfusions, hydroxyurea, and splenectomy are commonly used in the management of CEP. Currently, the only available curative treatment of CEP is hematopoietic stem cell transplantation (HSCT). In this article, we present a young girl in which precocious genetic testing enabled early diagnosis and allowed curative treatment with HSCT for CEP at the age of 3 months of age, that is, the youngest reported case thus far.
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