Thrombotic Events In Children Research Articles

The role of coagulation factors VIII, IX and XI in the prediction and mediation of recurrent thrombotic events in children with non-central venous catheter deep vein thrombosis

BackgroundThe role of elevated coagulation factors VIII (FVIII), FIX, FXI for the prediction of recurrent thrombotic events in children after an index non-central venous catheter (non-CVC) related deep vein thrombosis (DVT) remains unclear. ObjectiveThis study investigates the predictive role of FVIII, FIX, and FXI for recurrent thrombosis in children with index non-CVC DVTs, and the mediation effect of FVIII on chronic inflammation and recurrent thrombosis. MethodsChildren aged 0–18 years diagnosed with an index non-CVC related DVT (1993–2020) were included in this single-center retrospective cohort study. Plasma levels of FVIII, FIX, FXI were measured cross-sectionally ≥30 days after the acute DVT. The association between the continuous variables FVIII, FIX, FXI and thrombosis recurrence was investigated using uni- and multivariable logistic regression, adjusting for age, sex, and chronic inflammation. Mediation analysis assessed the role of FVIII as a mediator between chronic inflammation and recurrent thrombosis. Ethics approval was obtained. ResultsA total of 139 children with an index non-CVC related DVT were included. Thirty-eight (27 %) had a recurrent thrombosis at a median of 237 days (P25-P75 65-657 days) after the index DVT. In uni- and multivariable-analysis, FVIII, FIX or FXI did not predict thrombosis recurrence; However, chronic inflammation was an independent predictor. There was no evidence that FVIII mediated the effect of chronic inflammation on thrombosis recurrence. ConclusionWe found no evidence that elevated FVIII, FIX or FXI predicted thrombosis recurrence, or evidence of a mediating role of FVIII. Underlying chronic inflammation predicted venous recurrent thrombotic events in this cohort.

PB0289 Association of Elevated Coagulation Factors VIII, IX and XI with Recurrent Thrombotic Events in Children with Non-Central Venous Line Deep Vein Thrombosis

PB0289 Association of Elevated Coagulation Factors VIII, IX and XI with Recurrent Thrombotic Events in Children with Non-Central Venous Line Deep Vein Thrombosis

Thrombosis in Multisystem Inflammatory Syndrome Associated with COVID-19 in Children: Retrospective Cohort Study Analysis and Review of the Literature.

Background: The causative agent of the new coronavirus infection SARS-CoV-2 has unique properties causing hyperinflammatory syndrome and cytokine storm, as well as widespread endotheliitis and thrombotic microangiopathy, initially detected in the lungs of adult patients who died from a severe form of the disease. Venous and arterial thrombosis in adults were identified as common causes of severe complications and deaths in new coronavirus infections. There are very few reports of thrombotic events in children with COVID-19 in the literature. Methods: We conducted a retrospective analysis of the histories of 60 patients in the Irkutsk Regional Children's Clinical Hospital from November 2020 to November 2022 with a MIS-C diagnosis established according to WHO criteria, of which 8 (13.3%) were diagnosed with venous and/or arterial thrombosis, confirmed by laboratory and ultrasound and/or X-ray methods. Results: The average age of children with thrombosis (Me) was 7.5 years (min 4 months, max 17 years), with a M:F ratio of 3.0. Venous thrombosis was detected in six of the eight patients, including in the deep veins of the lower extremities in four. Pulmonary embolism occurred in two (one of them was fatal), and cerebral venous sinus thrombosis and thrombosis of the branches of the upper and lower vena cava were found in one patient. Extensive bilateral stroke due to thrombosis of the large cerebral arteries occurred in two patients, including one in combination with distal gangrene. Secondary thrombotic renal microangiopathy took place in three of the eight patients. Among these three, atypical HUS was diagnosed in one case. Multiple thrombosis involving the venous and arterial bed was detected in four of the eight patients. High levels of D-dimer, thrombocytopenia, increased NT-proBNP, cerebral coma, and aseptic meningitis were the events most often associated with thrombosis. All patients received immunomodulatory therapy (immunoglobulin, dexamethasone/methylprednisolone), pathogenetic therapy for multiorgan failure, anticoagulant therapy with heparin/LMWH, and acetylsalicylic acid. Biologics were used in two patients. Conclusions: The main predictors of thrombosis in children with MIS-C were increased D-dimer, thrombocytopenia, hospitalization in the ICU, and noncardiogenic pulmonary edema. Thrombosis of the deep veins of the lower extremities, large cerebral arteries, and secondary thrombotic microangiopathy was common. There was a single death (12.5% of the eight patients), associated with PE.

Cardiovascular Risk Factors and Family History of Major Thrombotic Events in Children with Migraine: A 12-Year Retrospective Single-Centre Study

Migraine is one of the most frequent primary headaches in childhood. The role of thrombotic predisposition in its pathogenesis is debated. Our aim was to analyse the cardiovascular risk factors and family history of major thrombotic events in children with migraine. A retrospective, single-centre study was performed over 12 years. Our headache centre record database was screened for migraine with aura (MA) and migraine without aura (MO) on the basis of the ICHD-II (until 2013) and III criteria. A control group of otherwise healthy children was recruited. Descriptive and multivariate analyses are provided; significance was set at p < 0.05. Migraine was diagnosed in 930 children (24.7% MA); 73.3% were 9-14 years old. Children with MA were older (p < 0.001). A family history of cerebral ischemic events at ≤50 years old was more commonly reported by children with MA than those with MO (p < 0.001) and those in the control group (p = 0.001). Children with MA showed a higher risk of a family history of cerebral ischemic events at ≤50 years old than children with MO (OR: 2.6) and those in the control group (OR: 3.1). When comparing the family history of DVT, we observed a significantly increased risk for MA vs. MO (OR: 2.9). A family history of cerebral ischemic events at ≤50 years old leads to an increased risk of MA. Further studies are needed to explore such an association.

Evaluation of antithrombotic prophylaxis and thrombotic events in children with COVID-19 or MIS-C: A tertiary pediatric center experience

ObjectivesCOVID-19 and multisystem inflammatory syndrome in children (MIS-C) are associated with a risk of hypercoagulability and thrombotic events. We aimed (a) to evaluate the demographic, clinical, and laboratory findings as well as the incidence of thrombotic events of COVID-19 and MIS-C in children and (b) to determine the role of antithrombotic prophylaxis. MethodsA single-center retrospective study evaluated hospitalized children with COVID-19 or MIS-C. ResultsThe study group consisted of 690 patients, 596 (86.4%) diagnosed with COVID-19 and 94 (13.6%) diagnosed with MIS-C. Antithrombotic prophylaxis was used for 154 (22.3%) patients: 63 patients (10.6%) in the COVID-19 group and 91 (96.8%) patients in the MIS-C group. Use of antithrombotic prophylaxis was statistically higher in the MIS-C group (p<0.001). Patients who received antithrombotic prophylaxis were of older median age, were more commonly male, and had more frequent underlying diseases than those without prophylaxis (p<0.001, p<0.012, p<0.019, respectively). The most common underlying condition was obesity in patients who received antithrombotic prophylaxis. Thrombosis was observed in one (0.2%) patient in the COVID-19 group with a thrombus in the cephalic vein, two (2.1%) patients in the MIS-C group, with a dural thrombus in one patient and a cardiac thrombus in the other patient. The patients with thrombotic events were previously healthy and had mild disease. ConclusionIn our study, thrombotic events were rare compared with previous reports. We used antithrombotic prophylaxis for most children with underlying risk factors; perhaps for this reason, we did not observe thrombotic events in children with underlying risk factors. We suggest that patients diagnosed with COVID-19 or MIS-C be closely monitored for thrombotic events.

The significance of D-dimer investigation in Iraqi children with COVID-19

Background: The proportion of children affected with COVID-19 accounted for approximately 1 to 2 % of all infected cases and the disease often follows a mild to moderate disease. Increased coagulation and events that are thrombotic were repeatedly recorded in adult patients with COVID-19. Nevertheless, till now, there is no consensus about thrombotic events in children in published articles. Aim of the study: to make evaluation of d-dimer level in children with COVID-19 and the rate of thrombotic complications. Patients and methods: The present research that is of cross sectional type was carried out in Children and Maternity Teaching Hospital in Al-Diwaniyah Province, Iraq. The study included 168 children with COVDI-19 proved by positive RT-PCR results following nasopharyngeal swabs. The age ranged from one month up to 15 years and the study included 77 girls and 91 boys. Results: The current study included 168 children affected by COVID-9. The median level of d-dimer in those enrolled children was 0.3 µg/ml with a range of 0.05 to 11 µg/ml. According to a cutoff value of &gt; 0.05 µg/ml, children were categorized into 73 (43.5 %) cases as having high d-dimer level and 95 (56.5 %) as having normal d-dimer level.

New Anticoagulants in Neonates, Children, and Adolescents.

Thrombotic events are an increasing challenge in pediatrics. Standard-of-care anticoagulants for pediatric thrombosis have several disadvantages which could be overcome by using direct oral anticoagulants (DOACs). Until recently, there was not enough evidence from clinical trials to recommend for or against the use of any of the four DOACs in children with thrombosis. In this literature review, we looked at the latest clinical trials in this field. On clinicaltrials.gov, we found 13 current studies with published results. For two of the four DOACs, namely dabigatran and rivaroxaban, we found successful phase III studies which led to the approval for the use in children. The results of these pivotal phase III studies allow to finally recommend rivaroxaban and dabigatran for the prophylaxis and treatment of thrombotic events in children.

Diagnostic pitfalls in child thrombosis

In recent years, we have seen an increase in thrombotic events in children, which creates difficulties in early diag­no­sis, especially in rare locations such as portal vein throm­bo­sis. The most common cause is represented by an­ti­phos­pho­lipid syndrome (APS), especially secondary to systemic lupus erythematosus (SLE). The investigation of the prothrombophilic pattern is mandatory in these pa­tients, the association being possible. The therapeutic ma­nage­ment is complex, in a multidisciplinary team, and will in­clude, in addition to chronic anticoagulation, an effective im­mu­no­sup­pression to control the degree of activity of the lupus disease.

Abstract 9192: Efficacy and Safety of Dabigatran in the Treatment and Secondary Prophylaxis of Children With Congenital Heart Disease

Introduction: Congenital heart disease (CHD) is associated with an increased frequency of thrombotic events in children, particularly in cyanotic conditions (i.e., single ventricles). Phase IIb/III clinical trials in children with venous thromboembolism (VTE) reported the noninferiority of dabigatran etexilate (DE) versus standard of care in treating acute VTE (DIVERSITY, NCT01895777) and a favorable safety profile for VTE prevention (NCT02197416). Aim: To evaluate the efficacy and safety of DE in the treatment and secondary prophylaxis of VTE in children with CHD, including subsets with cyanotic CHD. Methods: The primary composite efficacy endpoint in DIVERSITY was complete thrombus resolution and freedom from VTE recurrence or VTE-related death; safety endpoints included bleeding events (BEs). Primary endpoints in the VTE prevention trial were VTE recurrence and BEs. CHD status was confirmed locally using standard diagnostic modalities. Results: In DIVERSITY, 48/267 (18.0%) children had CHD. DE was noninferior to standard of care in both the CHD and non-CHD groups for the composite primary endpoint ( Table ), irrespective of the presence of cyanotic or noncyanotic CHD ( Table ). BEs (mainly minor) appeared to be lower in the CHD (8.3%) than the non-CHD group (25.7%), regardless of treatment. In the secondary VTE prevention trial, 17/211 (8.1%) children had CHD. Recurrent VTE at 12 months occurred in 0 and 3 (1.5%) children in the CHD and non-CHD groups respectively ( Table ). Conclusions: In children with CHD, DE has an efficacy and safety profile consistent with the overall DIVERSITY trial. Furthermore, our results confirm the safety profile for secondary VTE prevention, suggesting that DE is a viable anticoagulant alternative for this population.

Prevention of recurrent thrombotic events in children with central venous catheter-associated venous thrombosis

AbstractCentral venous catheters (CVC) are the most significant risk factor for pediatric venous thromboembolism (VTE). After an index CVC-associated VTE (CVC-VTE), the role of secondary prophylaxis for subsequent CVC placement is uncertain. Aims of this single-center retrospective study were to evaluate the efficacy of secondary prophylaxis for patients with a prior CVC-VTE and identify risk factors associated with recurrent VTE in patients less than 19 years with an index CVC-VTE between 2003 and 2013. Data collection included clinical and demographic factors, subsequent CVC placement, secondary prophylaxis strategy, recurrent VTE, and bleeding. Risk factors for recurrence and effectiveness of secondary prophylaxis were evaluated using survival and binomial models. Among 373 patients with an index CVC-VTE, 239 (64.1%) had subsequent CVC placement; 17.4% (65/373) of patients had recurrent VTE, of which 90.8% (59/65) were CVC-associated. On multivariable survival analysis, each additional CVC (hazards ratio [HR] 12.00; 95% confidence interval [CI] 2.78-51.91), congenital heart disease (HR 3.70; 95% CI 1.97-6.95), and total parenteral nutrition dependence (HR 4.02; 95% CI 2.23-7.28) were associated with an increased hazard of recurrence. Full dose anticoagulation for secondary prophylaxis was associated with decreased odds of recurrent CVC-VTE (odds ratio [OR] 0.35; 95% CI 0.19-0.65) but not prophylactic dosing (OR 0.61; 95% CI 0.28-1.30). Only 1.3% of CVCs experienced major bleeding with prophylactic or full-dose anticoagulation. In summary, children with CVC-VTE are at increased risk for recurrent VTE. Secondary prophylaxis with full-dose anticoagulation was associated with a 65% reduction in odds of thrombotic events.

Low molecular weight heparin for prevention of central venous catheter-related thrombosis in children.

The prevalence of children diagnosed with thrombotic events has been increasing in the last decades. The most common thrombosis risk factor in neonates, infants and children is the placement of a central venous catheter (CVC). It is unknown if anticoagulation prophylaxis with low molecular weight heparin (LMWH) decreases CVC-related thrombosis in children. This is an update of the Cochrane Review published in 2014. To determine the effect of LMWH prophylaxis on the incidence of CVC-related thrombosis and major and minor bleeding complications in children. Further objectives were to determine the effect of LMWH on occlusion of CVCs, number of days of CVC patency, episodes of catheter-related bloodstream infection (CRBSI), other side effects of LMWH (allergic reactions, abnormal coagulation profile, heparin-induced thrombocytopaenia and osteoporosis) and mortality during therapy. The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 7 May 2019. We undertook reference checking of identified trials to identify additional studies. We included randomised controlled trials (RCTs) and quasi-randomised trials comparing LMWH to no prophylaxis (placebo or no treatment), or low-dose unfractionated heparin (UFH) either as continuous infusion or flushes (low-dose UFH aims to ensure the patency of the central line but has no systemic anticoagulation activity), given to prevent CVC-related thrombotic events in children. We selected studies conducted in children aged 0 to 18 years. Two review authors independently identified eligible studies, which were assessed for study methodology including bias, and extracted unadjusted data where available. In the data analysis step, all outcomes were analysed as binary or dichotomous outcomes. The effects of interventions were summarised with risk ratios (RR) and their respective 95% confidence intervals (CI). We assessed the certainty of evidence for each outcome using the GRADE approach. One additional study was included for this update bringing the total to two included studies (with 1135 participants). Both studies were open-label RCTs comparing LMWH with low-dose UFH to prevent CVC-related thrombosis in children. We identified no studies comparing LMWH with placebo or no treatment. Meta-analysis found insufficient evidence of an effect of LMWH prophylaxis in reducing the incidence of CVC-related thrombosis in children with CVC, compared to low-dose UFH (RR 0.68, 95% CI 0.27 to 1.75; 2 studies; 787 participants; low-certainty evidence). One study (158 participants) reported symptomatic and asymptomatic CVC-related thrombosis separately and detected no evidence of a difference between LMWH and low-dose UFH (RR 1.03, 95% CI 0.21 to 4.93; low-certainty evidence; RR 1.17, 95% CI 0.45 to 3.08; low-certainty evidence; for symptomatic and asymptomatic participants respectively). There was insufficient evidence to determine whether LMWH impacts the risk of major bleeding (RR 0.27, 95% CI 0.05 to 1.67; 2 studies; 813 participants; low-certainty evidence); or minor bleeding. One study reported minor bleeding in 53.3% of participants in the LMWH arm and in 44.7% of participants in the low-dose UFH arm (RR 1.20, 95% CI 0.91 to 1.58; 1 study; 158 participants; very low-certainty evidence), and the other study reported no minor bleeding in either group (RR: not estimable). Mortality during the study period was reported in one study, where two deaths occurred during the study period. Both were unrelated to thrombotic events and occurred in the low-dose UFH arm. The second study did not report mortality during therapy per arm but showed similar 5-year overall survival (low-certainty evidence). No additional adverse effects were reported. Other pre-specified outcomes (including CVC occlusion, patency and CRBSI) were not reported. Pooling data from two RCTs did not provide evidence to support the use of prophylactic LWMH for preventing CVC-related thrombosis in children (low-certainty evidence). Evidence was also insufficient to confirm or exclude a difference in the incidence of major and minor bleeding complications in the LMWH prophylaxis group compared to low-dose UFH (low and very low certainty respectively). No evidence of a clear difference in overall mortality was seen. Studies did not report on the outcomes catheter occlusion, days of catheter patency, episodes of CRBSI and other side effects of LMWH (allergic reactions, abnormal coagulation profile, heparin-induced thrombocytopaenia and osteoporosis). The certainty of the evidence was downgraded due to risk of bias of the included studies, imprecision and inconsistency, preventing conclusions in regards to the efficacy of LMWH prophylaxis to prevent CVC-related thrombosis in children.

Use of Direct Oral Anticoagulants in Children and Adolescents.

While the need for anticoagulation in children has increased over the last decades, dose regimens of currently used anticoagulants, including low-molecular-weight heparin (LMWH) and vitamin K antagonist (VKA), are still extrapolated from adult guidelines because well-designed clinical trials were never performed in children. This approach is not optimal due to specific pediatric features of the hemostatic system and pathophysiology of thrombosis. These anticoagulants also present several disadvantages that further hamper optimal anticoagulation of pediatric patients, especially newborns and infants. The new direct oral anticoagulants (DOACs), which have the potential to overcome these disadvantages, were extensively investigated in adults and have become a valid alternative to LMWH and VKA for anticoagulation in the adult population. Several pediatric trials on all approved DOACs are currently ongoing, providing specific pediatric formulations and age- and weight-adjusted dose guidelines. First results of phase III trials indicate that DOACs are at least as efficient and safe as LMWH and VKA for the treatment and prevention of thrombotic events in children with different clinical conditions. This review article summarizes available data from terminated and ongoing controlled trials on DOACs in children and adolescents.

The Frequency of Thromboembolic Complications in Pediatric Nephrotic Syndrome

Background: Nephrotic syndrome (NS) is a common renal disease in the pediatric population, which can be complicated with venous thromboembolic events. Objectives: In the present study, the researchers evaluated the risk factors of venous thrombotic events in children with nephrotic syndrome. Methods: In this descriptive cross sectional study, the researchers evaluated 43 cases of NS including 35 uncomplicated and eight complicated patients with venous thrombotic events, who were admitted to the nephrology ward of Ali-Asghar Children Hospital from 2011 to 2015. Two groups were matched for age onset of NS. Data were recorded on age, gender, body mass index (BMI), histopathologic varieties of NS, and serum albumin level. Results: The mean age of cases with venous thrombotic events was 7.31 ± 4.1 years. There were six females. Of eight cases with venous thrombotic events, five cases suffered of pulmonary thromboembolism (PTE) and five cases of deep vein thrombosis (DVT). The mean serum albumin level in the thrombotic group was 1.87 ± 0.4 g/dL. The histopathologic results showed two cases of membranous proliferative glomerulonephritis (MPGN), three cases of minimal change disease (MCD) and one case of focal segmental glomerulosclerosis (FSGS). The researchers found significant differences between mean serum albumin level and histopathologic results in the case and control groups. Conclusions: Venous thrombosis and pulmonary emboli are important complications in pediatric NS. The risk of VTE increases with lower serum albumin level. The risk of VTE increases with lower serum albumin level. The researchers suggest the use of anti-thrombotic agents as prophylaxis in nephrotic patients with serum albumin level of less than 2 g/dL. Copyright © 2019, Journal of Comprehensive Pediatrics.

Assessment of thrombotic events in children: A hospital based study

Background: There is scarcity of information on the incidence of inherited thrombophilia from our country. The present study was conducted to assess thrombotic events in children. Materials & Methods: The present study was conducted in the department of Pediatrics. It comprised of 38 children. Patients were subjected to complete hemogram, sickling test, immunological evaluation etc. Risk factors for thrombotic events were recorded. Results: Out of 38 patients, 16 were of VTE and 22 were of ATE. The most common VTE was due to central venous catheter seen in 6 cases. Most common ATE was due to thrombophilias seen in 5 cases. Other reasons in VTE were immobilization seen in 2, trauma in 1, infections in 2, dehydration in 2. Other reasons in ATE were immobilization seen in 2, trauma in 4, infections in 3, dehydration in 3 and unknown in 4 cases. The difference was significant (P< 0.05). Conclusion: Thrombotic events in children are emerging problem. The most common reason for VTE was central venous catheters and in ATE was thrombophilias.

RUNX1 Amplification Increases the Risk for Thrombosis in Children With B-cell Acute Lymphoblastic Leukemia.

RUNX1 (AML1) amplification in patients with B-cell acute lymphoblastic leukemia (B-ALL) has been associated with poor survival for unclear reasons. Our anecdotal experience suggests that children with B-ALL and RUNX1 amplification might be predisposed to thrombosis. We performed a retrospective cohort study of children with B-ALL treated from 2008 to 2014 at the North Carolina Children's Hospital. Patient demographics, cytogenetics, and diagnosis of thrombosis were extracted by blinded chart review. Analysis was performed examining the relationship between RUNX1 amplification and thrombosis. We identified 119 patients with B-ALL and a median age of 4.9 years (interquartile range, 2.9 to 8.6 y) at diagnosis. Four patients (3%) had RUNX1 amplification. The average number of RUNX1 copies among those with amplification was 5 (SD 0.81 [range, 4 to 6]). Eighteen thromboses were diagnosed within 6 months of starting treatment. These events were more likely among patients with RUNX1 amplification than in patients without amplification (75% vs. 13%; RR 5.75, 95% confidence interval, 2.75-12.01). RUNX1 amplification may predispose to early thrombotic events in children with B-ALL which could, in part, contribute to their poorer outcomes. Treatment implications, including possible prophylactic anticoagulation of patients with of RUNX1 amplification, justify larger studies to confirm these findings.

The significance of F139V mutation on thrombotic events in compound heterozygous and homozygous protein C deficiency.

Both compound heterozygous and homozygous protein C deficiencies (PCDs) can cause lethal thrombotic events in children. This study investigated the significance of F139V mutation in activation of protein C in heterozygous and biallelic PCD. Two pedigrees with three probands were recruited, including heterozygous, compound heterozygous, and homozygous PCD and non-PCD families. The plasma levels of protein C activity (PC:A), protein C antigen (PC:Ag), factor V:C, factor VIII:C, fibrinogen (FIB), and D-dimer (D-D) were measured. Prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT) were also detected. All nine exons of protein C gene (PROC) were sequenced. Protein C mutation, T>G at site 6128 (exon 7) resulting in F139V, was identified in both pedigrees. Heterozygous missense mutation F139V (n = 10) had 56.4% lower levels of PC:A and PC:Ag compared with members with wild-type PROC (n = 6). Biallelic compound heterozygous and homozygous PCDs with F139V (n = 3) significantly decreased the levels of PC:A and PC:Ag compared with heterozygous members (P < 0.05); however, these were not lethal. Heterozygous F139V mutations of PRO caused mild reduction of protein C function, which might be the reason for survival of compound heterozygous or homozygous PCD with F139V in adults.

No impact of endogenous prothrombotic conditions on the risk of central venous line‐related thrombotic events in children: results of the KIDCAT study (KIDs with Catheter Associated Thrombosis)

Central venous lines (CVLs) are the major exogenous risk factor for deep venous thrombosis (DVT) in children. The study objective was to assess whether endogenous prothrombotic conditions contribute to the risk of CVL-related DVT in children. This was a cohort study of consecutive children with heart disease requiring CVLs for perioperative care. CVLs were inserted percutaneously in the upper venous system and patients received prophylaxis with continuous unfractionated heparin (50ukg(-1) d(-1) ). Blood samples to test for prothrombotic conditions were collected prospectively and assayed in a blinded fashion. Outcome assessment was by screening for DVT by venography, venous ultrasound and echocardiography. The study population consisted of 90 children, median age 2.7years (0months-18years). Prevalence rates of antithrombin deficiency, protein C deficiency, protein S deficiency, heterozygous factor V Leiden, prothrombin G20210A mutation, methylentetrahydrofolate C677TT genotype, hyperhomocysteinemia, lupus anticoagulant, anticardiolipin antibodies and increased levels of lipoprotein (a) were within the range reported for the general population. At least one prothrombotic condition was present in 38% of children and combined abnormalities in 8%. The incidence of DVT was 28% (25/90), and most DVTs were asymptomatic. None of the prothrombotic conditions showed a significant association with DVT. The population attributable risk (i.e. the risk of DVT in the overall population attributable to a specific condition) did not exceed 2.2%. Prothrombotic conditions did not have an important impact on the risk of DVT in children with short-term CVLs. The results of the study suggest that screening for prothrombotic conditions is not justified in this setting.

Low molecular weight heparin for prevention of central venous catheterization-related thrombosis in children

The prevalence of children diagnosed with deep vein thrombosis or pulmonary embolism has been increasing in the last decade. The most common thrombosis risk factor in neonates, infants and children is the placement of a central venous catheter (CVC). To date, it is unknown if the practice of anticoagulation prophylaxis with low molecular weight heparin (LMWH) decreases CVC-related thrombosis in children. The primary objective of this review was to determine the effect of LMWH prophylaxis on reducing the incidence of CVC-related thrombosis in children.Secondary objectives were to determine the effect of LMWH on occlusion of CVCs, number of days of CVC patency, episodes of catheter-related sepsis, side effects of LMWH (allergic reactions, major and minor bleeding complications, abnormal coagulation profile, osteoporosis) and mortality during therapy. The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched June 2013), CENTRAL (2013, Issue 5) and clinical trial databases. The authors searched MEDLINE and EMBASE (July 2013). Bibliographies of identified articles were searched. There were no language restrictions. Randomised and quasi-randomised trials comparing LMWH prophylaxis to standard care given to prevent CVC-related thrombotic events in children were included. We selected studies conducted in children aged 0 to 18 years. Two review authors independently identified eligible studies, which were assessed for study quality including bias, and extracted unadjusted data where available. In the data analysis step, all outcomes were analysed as binary or dichotomous outcomes. The effects of interventions were summarised with risk ratios (RR) and their respective 95% confidence intervals (CI). One of 17 studies retrieved for full-text assessment for eligibility was included in the final analysis. This study included a total of 186 participants and investigated the effect of LMWH to prevent CVC-related thrombosis compared to standard care. The risk of bias of the study was assessed to be low, except for the unclear risk of selection bias (allocation concealment not reported) and detection bias since it was an open-label study. Nonetheless, outcome adjudication was blinded. However, overall the quality of the evidence was low due to the fact that the study was underpowered. The CIs for the risk of CVC-related thrombosis (symptomatic and asymptomatic events) were compatible with benefits of either LMWH (reviparin) or the control (RR for symptomatic thrombosis 1.03, 95% CI 0.21 to 4.93; RR for asymptomatic thrombosis 1.17, 95% CI 0.45 to 3.08). Similarly, only one patient in the standard care group suffered a major bleeding event, while minor bleeding was found in 53.3% of patients in the reviparin arm and in 44.7% of patients in the standard care arm (major bleeding RR 0.34, 95% CI 0.01 to 8.26; minor bleeding RR 1.20, 95% CI 0.91 to 1.58). Lastly, there were two deaths within the study and neither were the result of a venous thrombotic event (VTE), occurring in the standard care arm. No additional adverse effects were reported. Other pre-specified outcomes for this review were not reported. A single study reported imprecise effects for the risk of CVC-related thrombosis in children on a CVC anticoagulant prophylaxis regimen. The quality of the evidence was low due to the fact that the included study was clearly underpowered, hampering any conclusions in regards to the efficacy of LMWH prophylaxis to prevent CVC-related thrombi in children. Further prospective randomised studies are highly encouraged.

ABO Group As a Thrombotic Risk Factor In Children With Acute Lymphoblastic Leukemia: A Retrospective Study Of 523 Pediatric Patients

IntroductionChildren with acute lymphoblastic leukemia (ALL) are at high risk of thrombotic complications, resulting from multiple risk factors (including malignancy, medications, central venous access devices (CVADs) and inherent host characteristics). Several studies have investigated the role of ABO blood groups in the occurrence of thromboembolic events in adults. Non-O blood group has been associated with an increased risk of venous thromboembolism (VTE), with a compounding effect in the presence of thrombophilia or cancer. We hypothesized that among children with ALL receiving a standardized protocol, there would be an increased risk of thrombotic events in non-O blood group compared to O group patients. MethodsWe retrospectively reviewed medical charts of all children with ALL treated in our tertiary care center between 1995 and 2013 and identified those with an objectively confirmed VTE. Children were included in 3 different, but similar multiagent protocols (DFCI 95-01, 00-01 and 05-01). Patients were classified into O and non-O blood groups. Leukemia phenotype, risk category, age, gender, timing of thrombosis, localisation and thrombotic workup were also collected.Statistical analysisRisk factor for VTE was defined as a prevalence. Univariate and multivariate logistic regression models were applied to assess the association between potential risk factors and the occurrence of VTE. Results are presented as adjusted OR and 95% confidence intervals. All statistical tests were two-sided. ResultsOf 523 children with ALL, 50 (9.6%) had thrombosis. Blood group distribution showed 38 (76%) patients in the non-O and 12 (24%) in the O group, compared to 302 (58%) non-O and 221 (42%) O in the total cohort. Except for gender, univariate predictors of VTE were all significant (age ≥ 10 years, P = 0.023, high risk category, P = 0.001, T phenotype, P = <0.001, non-O blood group, P = 0.006, male, P = 0.79). In multivariate analysis, non-O blood group, phenotype and risk category remained significant, but not age nor gender: age ≥ 10 years, OR 1.12 [95% CI 0.53,2.34]; high risk, OR 2.45 [95% CI 1.13,5.34]; T phenotype, OR 2.48 [95% CI 1.11,5.55]; non-O blood group, OR 2.93 [95% CI 1.46, 5.87]; male, OR 0.83[ 95% CI 0.45, 1.54] (table I). The vast majority of VTE occurred at an upper limb CVAD site (64%). Other sites were lower limb (14%), cerebral venous sinus thrombosis (14%), pulmonary embolism (6%), intracardiac (6%) and multiple sites (10%). VTE mainly occurred during the induction (18%) and consolidation (72%) phases of therapy. Thrombotic workup was done in 33/50 patients, with 11 abnormal results (mostly non-diagnostic low Protein C or S levels and positive lupus anticoagulants). Positive family history was found in 2 cases, but not consistently explored. No patients had Factor V Leiden or II G20210A mutation.DiscussionThe estimated prevalence of VTE in children with cancer is 8% (compared with 0.7-1.4/100 000 in the general pediatric population (Athale and Chan, 2003). A large number of studies have evaluated the epidemiology and risk factors of thrombotic events in children with ALL (Caruso et al 2006, Farinasso et al, 2007, Grace et al, 2011), confirming the multifactorial etiology of VTE in these children. Significant associations between ABO blood group and VTE have been reported in several studies (Dentali et al, 2012, T.Ohira et al, 2006 and 2007, Wu O et al, 2008, Wiggins KL et al, 2009). A few studies have investigated ABO blood group as a risk factor for VTE in adult malignancies (Streiff et al, 2004,). To date, none have explored it in childhood cancer. Our results clearly identify non-O blood group as a significant independent risk factor for VTE in children with ALL. Prospective studies are needed to confirm these data. The mechanisms underlying the increased risk of VTE in non-O blood group patients remain to be elucidated. Disclosures:No relevant conflicts of interest to declare.

Venous Thrombotic Events in Hospitalized Children and Adolescents With Inflammatory Bowel Disease

Adults with inflammatory bowel disease (IBD) have an increased risk of venous thrombotic events (TEs). We sought to evaluate the risk for TE in children and adolescents with IBD using a large population database. The triennial Healthcare Cost and Utilization Project Kids' Inpatient Database was used in a retrospective cohort study of hospitalized children in the United States across 1997, 2000, 2003, 2006, and 2009. Billing codes were used to identify discharges with Crohn disease, ulcerative colitis, pulmonary embolism, deep vein thrombosis, thrombophlebitis, thrombosis of intracranial venous sinus, Budd-Chiari syndrome, and portal vein thrombosis. A logistic regression model was fitted to quantify the increased risk of TE in children with IBD, while adjusting for other risk factors of thrombosis. The total weighted number of pediatric discharges was 7,448,292, and 68,394 (0.92%) were identified with IBD. The incidence of any TE in a hospitalized child or adolescent with IBD was 117.9/10,000 with a relative risk (95% confidence interval) of 2.36 (2.15-2.58). The adjusted odds ratio for any TE in a patient with IBD without surgery was 1.22 (1.08-1.36). Risk factors for TE among patients with IBD include older age, central venous catheter, parenteral nutrition, and an identified hypercoagulable condition. There is an increasing trend of TE in both the IBD and non-IBD patients. Hospitalized children and adolescents with IBD are at increased risk for TE. Conservative methods of TE prevention including hydration, mobilization, or pneumatic devices should be considered in hospitalized patients with IBD.