Venous Thrombosis In Children Research Articles

Cerebral venous thrombosis in children an 18-year review of a Portuguese hospital

IntroductionCerebral venous thrombosis (CVT) is an uncommon and clinically heterogeneous cerebrovascular particularly in children, only a few published case series focused in the pediatric population. Patients and methodsRetrospective single-center observational and analytical study of consecutive pediatric patients admitted in a level II Portuguese hospital with a confirmed diagnosis of CVT, from 2003 to 2021. Clinical presentation, neuroimaging findings, prothrombotic factors, treatment strategies, outcome and recanalization were documented. ResultsTwelve children were included (58% female). Mean age was 7.3 years. The most frequent symptoms were vomiting, headache and behavioral alterations. Infection was the triggering factor in 50% of the cases. The diagnosis of CVT was made based on imaging evidence of thrombosis through magnetic imaging resonance (MRI) with venography and/or computed tomography (CT) with venography. In 67% of cases there were multiples sinuses involved; the transverse sinus was the most affected, followed by the sigmoid sinus. In 83% of cases anticoagulant therapy was initiated with low molecular weight heparin (LMWH) and associated prothrombotic factors were investigated, with no major prothrombotic factors identified. No deaths occurred, but 30% had long-term neurological sequelae. One patient recurred 18 years later. ConclusionThe results of this study are consistent with data from other published studies. MRI is the preferred imaging method for diagnosis in children by avoiding ionizing radiation and allowing identification of subjacent causes. Anticoagulation with LMWH is recommended and important to reduce mortality and sequelae. Infectious diseases are the most common trigger for CVT and can also be the cause for high morbidity and poor outcomes.

Cerebral Sinus Venous Thrombosis in Pediatric Acute Lymphoblastic Leukemia: Incidence, Clinical Characteristics, and Long-term Neurologic Outcomes.

To describe the incidence, clinical characteristics, and long-term outcomes of cerebral sinus venous thrombosis in children with acute lymphoblastic leukemia. This was a retrospective cohort study comprising pediatric patients with newly diagnosed or first-relapse acute lymphoblastic leukemia who developed cerebral sinus venous thrombosis at Texas Children's Hospital from 2002 to 2019. Nineteen cases (1.7%) with cerebral sinus venous thrombosis were identified in all pediatric patients with acute lymphoblastic leukemia (n = 1129). Increased risk of cerebral sinus venous thrombosis was observed with age >10 years (P = .006). Twelve cases (63%) occurred during the induction, 4 (21%) during maintenance, and 3 (16%) during the consolidation phases of leukemia therapy. Seizures (10/19) and headaches (9/19) were the most common presenting symptoms. After treatment with anticoagulation therapy, we observed full resolution of thrombosis in 10 (53%) and partial resolution in 8 patients (42%). Long-term neurologic outcomes at follow-up in the 14 patients who survived included normal neurologic examinations (n = 10), epilepsy (n = 3), and focal neurologic deficits (n = 2). The death occurred in 5 individuals. Cerebral sinus venous thrombosis is a notable complication of pediatric acute lymphoblastic leukemia therapy. Older age (>10 years) was a risk factor for developing cerebral sinus venous thrombosis. Despite variable patient presentations and treatment durations, favorable clinical outcomes were observed in most patients after the treatment with anticoagulation for a minimum of 3 months.

Association of genetic variants of hemostatic system genes with venous thrombosis in children born to mothers with a burdened obstetric and gynecological history

Association of genetic variants of hemostatic system genes with venous thrombosis in children born to mothers with a burdened obstetric and gynecological history

Genomic analysis of venous thrombosis in children with acute lymphoblastic leukemia from diverse ancestries.

Venous thrombosis is a common adverse effect of modern therapy for acute lymphoblastic leukemia (ALL). Prior studies to identify risks of thrombosis in pediatric ALL have been limited by genetic screens of pre-identified genetic variants or genome- wide association studies (GWAS) in ancestrally uniform populations. To address this, we performed a retrospective cohort evaluation of thrombosis risk in 1,005 children treated for newly diagnosed ALL. Genetic risk factors were comprehensively evaluated from genome-wide single nucleotide polymorphism (SNP) arrays and were evaluated using Cox regression adjusting for identified clinical risk factors and genetic ancestry. The cumulative incidence of thrombosis was 7.8%. In multivariate analysis, older age, T-lineage ALL, and non-O blood group were associated with increased thrombosis while non-low-risk treatment and higher presenting white blood cell count trended toward increased thrombosis. No SNP reached genome-wide significance. The SNP most strongly associated with thrombosis was rs2874964 near RFXAP (G risk allele; P=4x10-7; hazard ratio [HR] =2.8). In patients of non-European ancestry, rs55689276 near the α globin cluster (P=1.28x10-6; HR=27) was most strongly associated with thrombosis. Among GWAS catalogue SNP reported to be associated with thrombosis, rs2519093 (T risk allele, P=4.8x10-4; HR=2.1), an intronic variant in ABO, was most strongly associated with risk in this cohort. Classic thrombophilia risks were not associated with thrombosis. Our study confirms known clinical risk features associated with thrombosis risk in children with ALL. In this ancestrally diverse cohort, genetic risks linked to thrombosis risk aggregated in erythrocyte-related SNP, suggesting the critical role of this tissue in thrombosis risk.

Protein C deficiency in a child with inferior vena cava thrombosis following abdominal trauma

There are very few data in the literature describing the occurrence of venous thrombosis in children. This raises the essential problem of late diagnosis, especially in asymptomatic or pauci-symptomatic presentations where this pathology may be unrecognized. The post-traumatic context of venous thrombosis in children, reported in a few cases, should lead to the suspicion of thrombophilia and to a clinical, biological and radiological etiological assessment. We report in our work the observation of a 14-year-old girl admitted in the context of a polytrauma with minimal mechanism in whom the lesion assessment revealed an extensive thrombosis of the inferior vena cava in the supra renal area, with a review of the literature.

Special Deep Vein Thrombosis in a Child: A Case Report

Background: Agenesis of the inferior vena cava (IVC) is an extremely rare congenital malformation. Although frequently symptomatic, due to its low prevalence, agenesis of IVC may often be missed in the normal workup. Most of the reports are related to the loss of IVC alone, while the reports of simultaneous loss of IVC and bilateral iliac veins are rare. Acute deep venous thrombosis is also one of the causes of chronic deep venous ulcer, especially in children with acute deep venous thrombosis, which is an important cause of neglect and missed diagnosis. When color Doppler ultrasound cannot be clear, attention must be paid to computerized tomography examination. Case Presentation: We reported a case of IVC below renal vein hypoplasia in an 8-year-old girl who presented bilaterally with persistent pain in both lower limbs. Ultrasonography revealed no clear IVC and iliofemoral venous system under the renal venous plane. Conclusion: This case is a rare congenital malformation of IVC. It is rare in children with venous thrombosis-related symptoms. We intended to demonstrate the etiology of the appearance of venous thrombosis in children through this case.

Cerebral venous thrombosis in children an 18-year review of a Portuguese hospital

IntroductionCerebral venous thrombosis (CVT) is an uncommon and clinically heterogeneous cerebrovascular particularly in children, only a few published case series focused in the pediatric population. Patients and methodsRetrospective single-center observational and analytical study of consecutive pediatric patients admitted in a level II Portuguese hospital with a confirmed diagnosis of CVT, from 2003 to 2021. Clinical presentation, neuroimaging findings, prothrombotic factors, treatment strategies, outcome and recanalization were documented. ResultsTwelve children were included (58% female). Mean age was 7.3 years. The most frequent symptoms were vomiting, headache and behavioral alterations. Infection was the triggering factor in 50% of the cases. The diagnosis of CVT was made based on imaging evidence of thrombosis through magnetic imaging resonance (MRI) with venography and/or computed tomography (CT) with venography. In 67% of cases there were multiples sinuses involved; the transverse sinus was the most affected, followed by the sigmoid sinus. In 83% of cases anticoagulant therapy was initiated with low molecular weight heparin (LMWH) and associated prothrombotic factors were investigated, with no major prothrombotic factors identified. No deaths occurred, but 30% had long-term neurological sequelae. One patient recurred 18 years later. ConclusionThe results of this study are consistent with data from other published studies. MRI is the preferred imaging method for diagnosis in children by avoiding ionizing radiation and allowing identification of subjacent causes. Anticoagulation with LMWH is recommended and important to reduce mortality and sequelae. Infectious diseases are the most common trigger for CVT and can also be the cause for high morbidity and poor outcomes.

Isolated splenic vein thrombosis as a complication of abdominal trauma in a 3-month-old girl

Falls from heights and traffic accidents are the most common causes of splenic damage. Abdominal trauma can cause splenic rupture or splenic vein thrombosis. About 11–55% of children with splenic vein thrombosis develop collateral circulation, leading to gastric and/or oesophageal varicose veins. Venous thrombosis in children can be also caused by congenital factors associated with coagulation disorders. The paper describes a case of a 3-month-old girl who developed isolated splenic vein thrombosis after a fall from height. Laboratory and genetic findings excluded thrombophilia. A 3-month anticoagulant treatment was administered. Gradual reduction in splenic size and the development of collateral circulation were observed in subsequent ultrasound scans. The girl remains under the care of a surgical clinic. The presented case of an infant with splenic vein thrombosis draws attention to possible complications of abdominal trauma after a fall from height.

Addendum to British Society for Haematology guideline on the investigation, management and prevention of venous thrombosis in children (Br. J. Haematol. 2011; 154: 196-207).

Addendum to British Society for Haematology guideline on the investigation, management and prevention of venous thrombosis in children (Br. J. Haematol. 2011; 154: 196-207).

Validation of Outcome Instruments for Venous Thrombosis in Children

Background: The sharply increasing rate of venous thrombotic events (VTE) in children makes the development and validation of outcome instruments critical for future research and care. To date, there are insufficient validated tools to assess children following VTE. This has resulted in widely varied reported rates of post thrombotic syndrome (PTS) in children ranging from 10 to 70%, and a poor understanding of quality of life (QoL) outcomes in children following VTE.Methods: A clinical cohort of 85 children < 21 years of age with a history of VTE and 60 healthy pediatric controls from three tertiary care thrombosis clinics were enrolled in a consented, non-interventional study of PTS outcomes. All cases and controls were assessed using two previously published pediatric PTS scales (Manco-Johnson (MJ) and Modified Villalta (MV)), a generic pediatric health-related QoL scale (PedsQL) and a new venous specific QoL scale derived from a validated adult scale (Peds VEINES QL) [Goldenberg, Haematologica 2010; Kahn JTH 2006; Kahn J Clin Epidemiol 2006]. Forty-nine of the original cohort were assessed again by a second examiner 2 to 4 weeks later. Inter-rater reliability, test-retest reliability, content validity, construct validity, and convergent validity were assessed for each measurement instrument.Results: Using the MJ scale, 18.8% of children demonstrated physical signs of PTS with concomitant pain limiting participation. Using the MV 50.6% had mild PTS, 5.9% moderate and 1.2% severe. Pain was not a required element for any level of severity in the MV. The reliability and internal validity of all four measurement instruments was confirmed with standard psychometric tests (Table 1). All four instruments had high construct validity, with significant differences in outcomes between controls and the clinical VTE cohort (Table 2). Convergent validity was also confirmed with significant correlations between all four instruments (Table 3).Discussion: All four instruments demonstrated strong reliability between raters and over time. All four had high discriminability for children with PTS relative to healthy controls. The MJ instrument identified a functional outcome of pain limiting participation along with physical findings. The proportion of the VTE population positive for PTS using the MJ instrument was closer to the reported pediatric weighted mean [Goldenberg, above]. The MV identified some PTS in a majority of children following a VTE episode while not discriminating functional outcomes. Additionally, while all four instruments were significantly correlated with each other, the newly created Peds VEINES QL had higher convergent validity than the more general PedsQL. This indicates that the new PTS specific QoL scale provides a more accurate representation of the impact of PTS on QoL than more generic pediatric QoL scales. [Display omitted] DisclosuresBrandao:Boehringer Ingelheim: Consultancy, Research Funding.

Iron-deficiency anaemia in childhood: a risk factor for severe venous thrombosis?

ABSTRACT Iron deficiency anaemia is a common disorder in the paediatric age-group. The association between iron deficiency and venous thrombosis in children without an underlying illness is rare. Two cases are described. A 17-year-old girl had been taking oestrogen-progestogen therapy for contraception for about 2 years and developed a lower-limb deep vein thrombosis associated with pulmonary embolism. A 3-year-old girl was admitted to the paediatric emergency department with pallor, weakness and vomiting, and a cerebral CT showed a recent cerebral venous thrombosis. Both cases had severe iron-deficiency anaemia which increases a thrombotic tendency and could be a further crucial trigger of venous thrombosis in patients at low risk; therefore, in cases of unexplained thrombosis, it must always be considered to be a risk factor. Abbreviations APCR: activated protein C resistance; CMV: cytomegalovirus; CT: computerised tomography; CVST: cerebral venous sinus thrombosis; CVT: cerebral venous thrombosis; DVT: deep vein thrombosis; DOACs: direct oral anticoagulants; EBV: Epstein–Barr virus; ID: iron deficiency; IDA: iron deficiency anaemia; LMWH: low molecular weight heparin; PE: pulmonary embolism; RDW: red blood cell distribution width; VT: venous thrombosis

The role of thrombophilia genes in the clinical implementation of arterial and venous thrombosis in newborns

The article considers the analysis results of the occurrence frequency of genotypes and alleles of plasma, platelet and fibrinolytic hemostasis in full-term newborns with arterial and venous thrombosis of various localization. Gene polymorphisms were studied by real-time PCR in human DNA samples obtained from buccal epithelium and venous blood lymphocytes. The control group was a group of healthy full-term newborns from families without a thrombophilic history. Predictors of arterial and venous thrombosis in children are such as polymorphism of the plasminogen activator inhibitor gene PAI-1-675 4G/4G (OR=5,6 [2,3-13,8]), combinations of polymorphisms PAI-1-675 4G/4G + factor VII G10976A G/G (OR=5,8 [1,7-19,1]), combinations of polymorphisms PAI-1 -675 4G/4G + factor VII G10976A G/G + factor XIII Val34Leu G/G (% AR=61), fibrinogen FGB -455 G/A (OR=3,75 [1,4-9,4]) and integrin alpha 2 ITGA2 807 T/T (OR=15,56 [1,9-126,7]). Thus, the study of polymorphisms of the plasminogen activator inhibitor, fibrinogen, integrin alpha 2 can serve as one of the criteria for identifying a high-risk group for the development of arterial and venous thrombosis in newborns and should be taken into account when evaluating individual thrombophilia risk.

Role of Low Albumin Levels in Pediatric Patients with Central Venous Catheters at Risk for Thrombosis

Introduction: The incidence of venous thromboembolism (VTE) in children has been increasing by about 10% per year for the past decade. This rise in VTE in children is attributed to improved survival of pediatric subspecialty patients as well as increased utilization of life-saving measures such as central venous catheters (CVCs) that can lead to catheter related thromboses (CRTs). More than 50% of venous thromboses in children and 90% of thromboses in neonates are CRTs, making catheter placement the single most significant risk factor for thrombosis in children. Association studies in adults have suggested an inverse relationship between serum albumin and risk of VTE. Given the paucity of data about albumin levels in pediatric patients in relation to VTE, we first performed a retrospective study to determine the prevalence of low albumin levels in pediatric patients with CRTs. We then initiated a prospective study to evaluate the incidence of hypoalbuminemia in pediatric patients at the time of CVC placement. Methods: We initially performed a retrospective study of 78 pediatric patients with a documented thrombotic event referred to the pediatric hematology service at University of Arizona between Aug 2014 and Jul 2017. Data collected included patient demographics, clinical diagnoses, type and location of thrombosis, presence or absence of a CVC, and albumin level within four days of the thrombotic event. We then designed a prospective study of pediatric patients undergoing CVC placement. Baseline data collected included patient demographics, clinical diagnoses, type of CVC placed, and laboratory results for albumin, factor VIII activity, D-dimer, and antithrombin activity within 4 days of CVC placement. Results: In the retrospective cohort of 78 consecutive pediatric patients with thrombosis, 84 thrombotic events were documented, of which 41 (49%) were CRTs. CRTs occurred in 22/35 (63%) patients less than 12 years of age and 14/42 (33%) patients aged 12 to 23 (P = 0.02). Serum albumin levels were available for 53 thrombotic events. Albumin levels were below the normal reference range in 27/30 (90%) of CRTs compared with 12/23 (52%) non-CRTs (P = 0.003). In the prospective study, data have been analyzed for the first 58 patients enrolled ages 2 months-17 years. At baseline, the prevalence of serum albumin below the lower limit of normal was 71% (41/58). Factor VIII activity was above 200% in 28/58 patients (48%), D-dimer was elevated in 48/58 patients (83%), and antithrombin was below 85% in 21/58 patients (36%). The mean duration of follow-up is 12 months. Four of the first 58 (6.9%) patients enrolled have had a CRT, all of whom had low albumin and elevated D-dimer levels at baseline. Conclusion: Hypoalbuminemia is highly prevalent in pediatric patients with thrombosis and also in patients with CVCs, who are at increased risk of thrombosis. In our retrospective analysis of pediatric patients with thrombosis, a low serum albumin level was documented in 74% of patients with thrombosis, including 90% of patients with a CRT. Preliminary analysis of the first 58 patients enrolled in a prospective study of patients with CVCs demonstrates a high prevalence (71%) of low albumin levels at the time of CVC placement. Further analysis is needed to define the value of serum albumin in thrombotic risk prediction and further explore potential prothrombotic mechanisms in CRT. Disclosures Lentz: Novo Nordisk Inc.: Consultancy, Honoraria, Research Funding.

Incidence of Deep Venous Thrombosis in Children after Colectomy for Inflammatory Bowel Disease: A Multicenter Study

Traynor, Michael D. MD; Polites, Stephanie F. MD; Bence, Christina MD; Muenks, Peter MA; Ha, Derrick BS; St Peter, Shawn D. MD, FACS; Landman, Matthew P. MD, MPH, FAAP, FACS; Densmore, John C. MD, FACS; Potter, D Dean MD Author Information

Venous thrombosis in children, adolescents and young adults with acute lymphoblastic leukemia receiving chemotherapy in the Republic of Belarus

Objective: to clarify the conditions for the occurrence of thrombosis and assess the effect of anticoagulant therapy on the survival and outcome of thrombosis in children, adolescents and young adults with acute lymphoblastic leukemia (ALL) receiving program chemotherapy.Materials and methods. The study included 592 patients with ALL received program chemotherapy from 2008 to 2017 in the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology (Minsk, Belarus). Of them, in 42 patients various localization venous thrombosis was detected at different therapy phase.Results.The cumulative detection rate of thrombosis was 7.5 ± 1.1 %. The use of pegelated asparaginase (PEG-asp) at a dose of 1000 IU/m2 in induction therapy increased the relative risk of thrombosis in the first 5 weeks of treatment by 3 times (relative risk 3.4; 95 % confidence interval 0.98–11.9), compared to patients not receiving PEG-asp. The cumulative detection rate of thrombosis in patients with the post-induction L-asparaginase (L-asp) 25,000 IU/m2 regimen was 14.7 ± 2.6 %, which was higher (p = 0.0536) than when using L-asp in other dosing regimens. In addition to ALL as the main disease, taking chemotherapy drugs, other risk factors for thrombosis (thrombophilia, the presence of antiphospholipid antibodies, a decrease of natural anticoagulants activity) in various combinations were in half (23 of 42) patients with venous thrombosis. Therapeutic dose of low molecular weight heparins (LMWH) 150–200 IU/kg received 30 patients. Reduced for the period of thrombocytopenia from 100 to 35 × 109/L for up to 4 weeks, a daily dose of LMWH was received by 12 patients. The dose of LMWH was reduced in proportion to the blood platelets count. After the recovery of the platelet count of more than 100 × 109/L, patients continued treatment of LMWH in a daily dose of 150–200 anti-Xa IU/kg. Reducing of LMWH dose during thrombocytopenia period did not affect the outcome of thrombosis (χ2 = 0.494; p = 0.78). Among 42 patients with thrombosis, 38 completed maintenance therapy, eventfree survival was 83.0 ± 8.0%, which did not differ (p = 0.654) from that (81.0 ± 2.0 %) in patients without thrombosis. Conclusion. The presence of venous thrombosis with the use of LMWH as antithrombotic therapy did not lead to a decrease in the event-free survival of ALL patients, compared with those without thrombosis. Reducing the therapeutic dose of LMWH did not affect the outcome of thrombosis in the analyzed groups.

Incidence of and risk factors for venous thrombosis in children with percutaneous non-tunnelled central venous catheters

BackgroundVenous thrombosis (VT) in children is often associated with a central venous catheter (CVC). We aimed to determine the incidence of VT associated with percutaneous non-tunnelled CVCs in a general paediatric population, and to identify risk factors for VT in this cohort. MethodsObservational, prospective study enrolling consecutive patients at a tertiary multi-disciplinary paediatric hospital. A total of 211 percutaneous, non-tunnelled CVCs were analysed. Data regarding potential risk factors for CVC-related VT were collected. Compression ultrasonography with colour Doppler was used to diagnose VT. ResultsOverall, 30.3% of children developed CVC-related VT, with an incidence rate of 29.6 (confidence interval, 22.5–36.9) cases/1000 CVC days. Upper body CVC location, multiple lumen CVCs, and male gender were independent risk factors for VT in multivariate analysis. All upper body VTs were in the internal jugular vein (IJV). The occurrence of CVC-related VT did not affect length of paediatric ICU or hospital stay. In patients with VT, femoral CVCs, young age, paediatric ICU admission, and a ratio of CVC/vein diameter >0.33 were associated with VT being symptomatic, occlusive, or both. IJV VT was often asymptomatic and non-occlusive. ConclusionsPaediatric non-tunnelled CVCs are frequently complicated by VT. Avoiding IJV CVCs and multiple lumen catheters could potentially reduce the overall risk of VT. However, IJV VT was more likely to be smaller and asymptomatic compared with femoral vein VT. More data are needed on the risk of complications from smaller, asymptomatic VT compared with the group of VT with symptoms or vein occlusion. Femoral vein CVCs and CVC/vein diameter >0.33 could be modifiable risk factors for VT with larger thrombotic mass. Clinical trial registrationACTRN12615000442505.

Venous Thrombosis in Children with Acute Lymphoblastic Leukemia Treated on DCOG ALL-9 and ALL-10 Protocols: The Effect of Fresh Frozen Plasma.

Background Venous thromboembolism (VTE) is an important complication for treatment of acute lymphoblastic leukemia (ALL) in children. Especially, ALL treatment, with therapeutics such as asparaginase and steroids, increases the thrombotic risk by reduction in procoagulant and anticoagulant proteins. Replacement of deficient natural anticoagulants by administration of fresh frozen plasma (FFP) may have a preventive effect on the occurrence of VTE. Methods We retrospectively analyzed all consecutive children (≤18 years) with ALL, treated on the Dutch Childhood Oncology Group (DCOG) ALL-9 and ALL-10 protocols at the Emma Children's Hospital Academic Medical Center between February 1997 and January 2012, to study the effect of FFP on VTE incidence, antithrombin and fibrinogen plasma levels, and VTE risk factors. Results In total, 18/205 patients developed VTE (8.8%; 95% confidence interval [CI]: 4.9–12.7%). In all patients, VTE occurred after asparaginase administration. In total, 82/205 patients (40%) received FFP. FFP supplementation did not prevent VTE or alter plasma levels of antithrombin or fibrinogen. In the multivariate analysis, VTE occurred significantly more frequently in children ≥12 years (odds ratio [OR]: 3.89; 95% CI: 1.29–11.73) and treated according to the ALL-10 protocol (OR: 3.71; 95% CI: 1.13–12.17). Conclusion FFP supplementation does not seem to be beneficial in the prevention of VTE in pediatric ALL patients. In addition, age ≥12 years and treatment according to the DCOG ALL-10 protocol with intensive and prolonged administration of asparaginase in combination with prednisone are risk factors. There is a need for effective preventive strategies in ALL patients at high risk for VTE.

Risk factors and diagnosis of severe deep venous thrombosis in children

Critically ill patients in PICU are at high risk of deep venous thromboembolism(DVT) and pulmonary embolism(PE). Sepsis and septic shock, central venous catheter, surgery and trauma, bed rest and immobilization, and the use of certain drugs(such as vasopressin) are high risk factors for DVT and PE.DVT or PE caused by mycoplasma infection is a new clinical problem in children.D-dimer is an important screening test for DVT, ultrasound doppler is the first choice of diagnostic examination, and venography is the gold standard for the diagnosis of DVT.In the current period, surveillance of high risk factors and earily diagnosis are the main strategies for DVT/PE.The efficacy of anticoagulants including unfractionated heparin and low-molecular-weight heparin in preventing DVT or PE in children needs further study. Key words: Deep venous thromboembolism; Pulmonary embolism; Risk factor; Critically ill; Children

The Effect of Anticoagulant Therapy on Survival and Outcome of Venous Thrombosis in Children, Teenagers, and Young Adults with Acute Lymphoblastic Leukemia Treated According to ALL-MB-2008 and ALL-MB-2015 Protocols

Aim. To assess the effect of anticoagulant therapy on survival and outcome of venous thrombosis in children, teenagers, and young adults with acute lymphoblastic leukemia (ALL). Materials &amp; Methods. Venous thrombosis was diagnosed in 42 out of 592 ALL patients treated according to ALL-MB-2008 and ALL-MB-2015 protocols from 2008 to 2017. Results. A daily dose of 150-200 lU/kg low molecular weight heparin (LMWH) was administered to 30 patients. Duration of anticoagulant treatment was up to 1 month in 4 patients, 2-3 months in 8 patients, 4-6 months in 12 patients, and 7-12 months in 4 patients. To 2 patients anticoagulants were administered for more than 24 months. Complete recanalization of thrombosed vessel was achieved in 19 patients, partial recanalization was achieved in 6 patients, obliteration of predominantly internal jugular vein was found in 5 patients. During thrombocytopenia (100 to 35 x 10&lt;sup&gt;9&lt;/sup&gt;/L) 12 patients received reduced doses of LMWH for 1-4 weeks. In the period of chemotherapy-induced thrombocytopenia the daily LMWH dose was reduced in proportion to thrombocyte level. After thrombocyte recovery up to more than 100 x 10&lt;sup&gt;9&lt;/sup&gt;/L antithrombotic treatment was continued with LMWH daily dose of 150-200 anti-Xa lU/kg. The duration of anticoagulant treatment among 12 patients who received reduced doses of LMWH was up to 1 month in 3 patients, 2-3 months in 4 patients, 4-6 months in 3 patients, and 7-12 months in 2 patients. Complete recanalization of thrombosed vessel was achieved in 8 patients, partial recanalization was achieved in 2 patients, vein obliteration was found in 2 patients. No correlation between LMWH dosage and thrombosis outcome was observed (χ&lt;sup&gt;2&lt;/sup&gt; = 0.494; p = 0.78). Maintenance (accompanying) therapy was completed in 38 out of 42 ALL patients with venous thrombosis. Event-free survival was 83 ± 8 %, that was similar to the one (81 ± 2 %) in patients without thrombosis (p = 0.654). Conclusion. Anticoagulant treatment of venous thrombosis complicating ALL in children, teenagers, and young adults did not yield a decrease of either overall or event-free survival. Reduction of LMWH doses in the period of chemotherapy-induced thrombocytopenia did not affect the outcome of venous thrombosis.

Mediastinal Mass, Triglycerides Level Above 1000mg/Dl and Intensive Dexamethasone and Asparaginase Treatment Are Risk Factors for Cerebral Sinus Venous Thrombosis in Children Treated for Acute Lymphoblastic Leukemia at the Children's Cancer Center of Lebanon

Background: Cerebral sinus venous thrombosis (CSVT) is a serious complication of childhood acute lymphoblastic leukemia (ALL) therapy. No universal consensus exists regarding its risk factors due to rarity of cases. The effect of CSVT on outcome is not limited to its own complications but extends to its possible negative impact on ALL therapy. Age above 10 years, T-cell immunophenotype and risk stratification (intermediate/high risk) were previously shown to be statistically significant risk factors for CSVT in our cohort of patients with an odds ratio of 3.56, 2.32 and 3.40 respectively and a P-Value of 0.03, 0.02 and 0.04 respectively (Ghanem et al. 2017).Aims and Methods: This is a prospective study of a pediatric cohort of children between 1 and 18 years of age treated for Acute Lymphoblastic Leukemia at the Children's Cancer Center of Lebanon (CCCL) between 2007 and 2017 with a protocol adopted from St Jude TOT XV. The aim of this analysis is to study the effect of decreasing asparginase and dexamethasone doses on the incidence of CSVT in addition to studying the effect of the following potential risk factors: presence of mediastinal mass at diagnosis, triglycerides level above 1000mg/dL and elevated initial blast count.In 2015, L-asparginase doses were decreased during induction from 10,000IU/m2/dose to 6,000IU/m2/dose and Dexamethasone doses were decreased from 12mg/m2/dose to 8mg/m2/dose for intermediate/high risk patients and from 8mg/m2/dose to 6mg/m2/dose for low risk patients. Patients were divided into two groups: group I for individuals treated between 2007 and 2015 and group I for individuals treated between 2015 and 2017.Results: A total of 202 patients were recruited (Group I, N=126 and Group II, N=76). The incidence of CSVT was 10.3% in group I and 1.3 % in group II. Univariate analysis showed that, treatment with intensive dexamethasone and asparginase in group I was a significant risk factor for CSVT (OR: 9.3, 95% CI: 1.2 - 72, P=0.03). Initial mediastinal mass (OR: 19.3, 95% CI: 5.4 - 68.6, P<0.0001) and triglycerides level above 1000mg/dL (OR: 3.4, 95% CI: 0.98 - 12, P=0.05) were also associated with increased risk of CSVT. Initial peripheral blast count ≥10,000 (OR: 0.57, 95% CI: 0.19 - 1.7, P=0.31), ≥50,000 (OR: 0.7, 95% CI: 0.14-3.35, P=0.66), and ≥100,000 (OR: 1.53, 95% CI: 0.29-7.82, P=0.61) were not risk factors for CSVT in our cohort.Conclusion: Decreasing the doses of dexamethasone and asparginase significantly lowered the risk of CSVT in our patient population. Initial mediatinal mass and triglycerides levels above 1000mg/dL during asaparginase therapy were significantly associated with increased risk of developing CSVT. If future studies confirm our findings, mediastinal mass and elevated triglycerides level may be considered amongst other factors predisposing to CSVT and may help identify candidates for thromboprophylaxis in the future. DisclosuresNo relevant conflicts of interest to declare.