Venous Thromboembolism In Pediatric Patients Research Articles

Duration of anticoagulation for venous thromboembolism in pediatric patients: Kids-DOTT trial outcomes at 2 years

BackgroundThe Kids-DOTT multinational, randomized clinical trial revealed noninferiority of a 6-week vs 3-month duration of anticoagulation for the treatment of provoked venous thromboembolism (VTE) in patients <21 years old in regard to net clinical benefit at 1 year. ObjectivesTo evaluate noninferiority at 2 years. MethodsPatients whose repeat imaging 6 weeks after VTE diagnosis did not show complete veno-occlusion were randomized to discontinue anticoagulation vs receive a total 3-month course and followed for 2 years for the occurrence of symptomatic recurrent VTE (efficacy outcome) and clinically relevant bleeding (safety outcome). Outcomes were centrally adjudicated, and net clinical benefit was compared between treatment arms via a prespecified bivariate noninferiority boundary, using 95% CIs in absolute risk differences between treatment arms. ResultsKaplan–Meier estimates of 2-year cumulative incidences in the 6-week and 3-month arms of the intention-to-treat population (n = 417) were 1.7% (95% CI, 0%, 3.7%) and 2.9% (95% CI, 0.3%, 5.4%), respectively, for symptomatic recurrent VTE and 1.1% (95% CI, 0%, 2.5%) and 3.2% (95% CI, 0.6%, 5.7%), respectively, for clinically relevant bleeding. Bivariate analysis of the absolute risk differences in the intention-to-treat population demonstrated that a 6-week anticoagulation duration was noninferior to a 3-month course. ConclusionThese findings support durability of the Kids-DOTT randomized clinical trial findings of net clinical benefit at 2 years.

Enoxaparin treatment dosing for venous thromboembolism in pediatric patients with obesity.

The optimal enoxaparin dosing for treatment of venous thromboembolism (VTE) in pediatric patients with obesity remains uncertain. We described the mean enoxaparin dose required to attain anti-factor Xa (anti-Xa) levels of 0.5-1unit/mL in pediatric patients with obesity. Pediatric patients with obesity (body mass index [BMI]≥95th percentile) who received treatment dose of enoxaparin from 2013 to 2022 and had at least one appropriately timed anti-Xa level were retrospectively evaluated. Daily enoxaparin dose required to achieve an anti-Xa level of 0.5-1unit/mL was reviewed and compared by the severity of obesity. The correlation coefficients between enoxaparin dose requirement and BMI, BMI percentile, and weight were measured by Spearman's rank correlation coefficient. Pediatric patients with obesity (n=89) required a mean enoxaparin dose of 0.8±0.18mg/kg twice daily to attain a therapeutic anti-Xa level. Children with BMI 95th-99th percentile and weight ≤100kg achieved the target level on a significantly higher weight-based enoxaparin dose compared to BMI greater than 99th percentile (0.95±0.15 vs. 0.75±0.15mg/kg twice daily; p<.001) and weight greater than 100kg (0.95±0.14 vs. 0.7±0.12mg/kg twice daily; p<.001). BMI, BMI percentile, and weight showed a moderate to strong negative correlation with enoxaparin dose requirement. Pediatric patients with obesity required a lower weight-based dose of enoxaparin to achieve a therapeutic anti-Xa than the recommended starting dose of 1mg/kg twice daily for treatment of VTE. Among obesity indices, weight showed the strongest negative correlation with total daily enoxaparin requirement.

Risk factors for venous thromboembolism in a single pediatric intensive care unit in China

BackgroundAnalyses of extensive, nationally representative databases indicate a rising prevalence of venous thromboembolism (VTE) among critically ill children. However, the majority of studies on childhood VTE have primarily concentrated on Caucasian populations in the United States and European countries. There is a lack of epidemiological studies on VTE in Chinese children.MethodsWe conducted a retrospective cohort study of data from the Pediatric Intensive Care (PIC) database. Data were obtained and extracted by using Structured Query Language (SQL) and the administrative platform pgAdmin4 for PostgreSQL. Bivariate analyses were conducted in which categorical variables were analyzed by a chi-square test and continuous variables were analyzed by a Student’s t-test. Separate multivariable logistic regressions were employed to investigate the associations between VTE and sociodemographic factors as well as clinical factors.ResultsOur study included 12,881 pediatric patients from the PIC database, spanning the years 2010 to 2018. The incidence rate of pediatric VTE was 0.19% (24/12,881). The venous thrombotic locations were deep venous thrombosis extremities (n = 18), superior vena cava (n = 1), cerebral sinovenous (n = 1), and other deep venous thrombosis (n = 4). Univariate analysis showed that age, weight, shock, sepsis, cancer and vasopressor receipt were statistically significant risk factors for pediatric VTE (all p ≤ 0.05). After multivariable logistic regression analysis, only shock (aOR: 6.77, 95%CI: 1.33–34.73, p = 0.019) and admission for sepsis (aOR: 6.09, 95%CI: 1.76–21.09, p = 0.004) were statistically significant associated with pediatric VTE.ConclusionsIn conclusion, data obtained from the Pediatric Intensive Care (PIC) database revealed a prevalence of VTE in pediatric patients of 0.19%. The most common location for venous thrombi was deep venous thrombosis (DVT) in the extremities. We identified that shock and sepsis were statistically significant factors associated with pediatric VTE.

Efficacy and Safety of Direct Oral Anticoagulants in Pediatric Venous Thromboembolism: A Systematic Review and Meta-Analysis.

To assess the efficacy and safety of direct oral anticoagulants (DOACs) in comparison to standard-of-care (SOC) anticoagulants in the management and prophylaxis of thromboembolic events in pediatric populations. A comprehensive search of electronic databases was conducted to identify relevant studies published between January 1, 2015, and December 18, 2022. A meta-analysis was undertaken to evaluate the effect of DOACs on clinically significant endpoints, employing trial-level data with harmonized endpoint definitions. The primary outcome was venous thromboembolism (VTE). Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. The study was registered with INPLASY (2022120065). Three studies encompassing 934 subjects were included. The incidence of VTE was reduced in patients administered DOACs compared to those on SOC anticoagulants (OR 0.41 [95% CI 0.19-0.93], I²=0%, P = 0.03). No significant differences were observed between the DOAC and SOC groups in all-cause mortality (OR 0.50 [95% CI 0.07-3.59], I²=0%, P = 0.35) or serious adverse events (OR 0.75 [95% CI 0.50-1.12], I²=0%, P = 0.16). The risk of major bleeding (OR 0.50 [95% CI 0.13-1.87], I²=44%, P = 0.30) and clinically relevant non-major bleeding (OR 1.23 [95% CI 0.50-3.00], I²=0%, P = 0.65) exhibited no significant differences between the groups. DOACs are associated with a reduced risk of VTE in pediatric patients without increasing the risk of bleeding, all-cause mortality, or serious adverse events when compared to SOC anticoagulants. DOACs may be an alternative for the treatment and prevention of thromboembolic events in the pediatrics.

Apixaban Is Effective and Safe in Reducing Venous Thromboembolism (VTE) in Obese Patients with Newly Diagnosed Pediatric Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma (ALL/LL) a Sub-Study Analysis of the Prevapix-ALL/Children's Oncology Group ACCL1333 Trial

Background: Pediatric patients with ALL/LL are at increased risk for VTE and obesity further increases VTE risk. Pediatric ALL/LL patients experiencing VTE have increased risk for mortality as compared to ALL/LL patients without VTE. Therefore, effective and safe pharmacologic VTE prevention options are urgently needed. The PREVAPIX-ALL trial was a multi-center, multinational, randomized, open-label, controlled trial assessing the safety and efficacy of primary prophylaxis using apixaban for the prevention of VTE in pediatric patients with ALL/LL. PREVAPIX-ALL was a collaboration between the Bristol Myers Squibb/Pfizer Alliance and the Children's Oncology Group. Patients with ALL/LL undergoing induction chemotherapy containing asparaginase therapy were randomized to either apixaban or standard of care (SOC - no anticoagulation). The objective of the current study was to separately analyze obese patients as a subgroup of the PREVAPIX-ALL trial. Aims: To assess the efficacy and safety of prophylactic apixaban vs. SOC for VTE prevention during induction chemotherapy in obese pediatric patients with ALL/LL. Methods: Obesity was defined as ≥ 95 th percentile for age and sex specific body mass index as per the Centers for Disease Control and Prevention childhood obesity definition. Patients newly diagnosed with ALL/LL, ages ≥ 1 to &amp;lt; 18 years, with a central venous line, and on induction chemotherapy with asparaginase were randomized to apixaban vs. SOC. Apixaban thromboprophylaxis was administered at a fixed dose per body weight until the end of induction when participants were screened for VTE. The primary efficacy outcome was a composite of symptomatic and asymptomatic VTE. The primary safety outcome was major bleeding, and the secondary safety outcome was a composite of major and clinically relevant non-major (CRNM) bleeding. Results: Out of 512 PREVAPIX-ALL participants, 498 (97.2%) were age 24 months or older with weight and height available. Of those, 82 were obese. Forty-two were randomized to apixaban and 40 were randomized to SOC (Table 1). For the primary efficacy outcome there was a statistically significant decrease in VTE events in the apixaban arm, 1/42 (2.4%) compared to the SOC arm 10/40 (25%) [RRR 91% (95% CI 3%, 99%) p 0.0067] (Table 2). No statistically significant difference was observed in bleeding between the two groups (Table 2). The mean apixaban exposure was similar among the obese and non-obese groups: obese apixaban mean exposure (SD) 23.4 days (5.55) and non-obese 23.5 days (6.44). No statistical difference was observed in the median steady-state area under the curve (AUC-TAU ng.h/mL) drug exposure between obese and non-obese categories stratified by age group on a linear scale: obese (n=38) 686.94 ng.h/mL (95% CI 397.8-1314.6) and non-obese (n=186) 663.50 ng.h/mL (95% CI 319.1-1090.9). Conclusion: Apixaban VTE prophylaxis in obese ALL/LL patients receiving asparaginase during induction chemotherapy resulted in a statistically significant 91% RRR in VTE compared to SOC. No statistical difference was observed in apixaban exposure days and AUC/TAU between obese and non-obese patients. Bleeding events were not increased in the apixaban arm as compared to SOC. Primary prophylaxis using apixaban safely reduces VTE in obese ALL/LL pediatric patients receiving induction chemotherapy containing asparaginase.

High Rates of Pediatric Venous Thromboembolism After Elective Laparoscopic Splenectomy Suggest Need for Perioperative Prophylaxis

IntroductionIn adult populations, postoperative venous thromboembolism (VTE) is a reported complication of up to 8% of elective laparoscopic splenectomy (LS) cases. VTE is a rare event in the pediatric population, affecting less than 1% of all pediatric surgical patients. We hypothesized that pediatric patients are at a higher risk of postoperative VTE after undergoing elective LS relative to other laparoscopic procedures and may warrant prophylactic treatment. Materials and methodsWe queried the American College of Surgeons National Surgical Quality Improvement Program-Pediatric (NSQIP-P) database from 2012 to 2020. Patients were identified using the Current Procedural Terminology code 38120 and only elective cases were analyzed. ResultsThe incidence of VTE in all pediatric patients undergoing surgery in the American College of Surgeons NSQIP-P database was 0.13%. The incidence of VTE in pediatric patients undergoing elective laparoscopic abdominopelvic procedures was 0.17%. There were seven total cases of VTE (0.41%) in pediatric patients undergoing elective LS, more than twice the rate of the general population (P = 0.001). Eighty percent of pediatric patients undergoing elective LS had an underlying hematological disorder. ConclusionsBy analyzing the NSQIP-P database, we evaluated the largest cohort of pediatric patients undergoing elective LS to date. We identified a higher incidence of VTE following this procedure relative to the rate of VTE in the overall population in the NSQIP-P database, as well as those undergoing elective laparoscopic abdominopelvic operations. The relatively higher incidence of VTE after elective LS is likely due to the presence of underlying hematological conditions. Given the low incidence of complications associated with pharmacologic VTE prophylaxis, the results of this study suggest that further research is warranted to establish the efficacy of perioperative pharmacological VTE prophylaxis in pediatric patients undergoing elective LS.

Recanalization of venous thromboembolism in pediatric patients undergoing anticoagulation therapy: A retrospective observational study

Recanalization of venous thromboembolism in pediatric patients undergoing anticoagulation therapy: A retrospective observational study

High rate of recurrent venous thromboembolism in children and adolescents with unprovoked venous thromboembolism

BackgroundUnprovoked venous thromboembolism (VTE) is rare in pediatrics. Current recommendations for anticoagulation duration after unprovoked VTE differ for pediatric and adult populations. ObjectivesThis single-center, retrospective cohort study aimed to determine the incidence rate of recurrent VTE in children and adolescents with unprovoked VTE, evaluate the potential risk factors for recurrence, and describe the anticoagulation regimens and bleeding in this population. MethodsChildren with an index, unprovoked VTE at the age of 1 to <21 years between 2003 and 2021 were included. The time to recurrent VTE and anticoagulation duration were summarized using Kaplan-Meier estimators. Clinical covariates were assessed for association with recurrence using stratified Kaplan-Meier curves and univariate Cox proportional hazards regression. ResultsEighty-five children met the inclusion criteria, and there were 26 recurrent events in 250 person-years of follow-up (incidence rate = 104 [95% CI, 71-153] per 1000 person-years). An age of ≥12 years at index VTE (hazard ratio [HR], 7.56; 95% CI, 1.60-35.83) and inherited thrombophilia (HR, 2.28; 95% CI, 1.05-4.95) were significantly associated with recurrent VTE. Female sex had a nonstatistically significant decreased hazard of recurrence (HR, 0.56; 95% CI, 0.25-1.27). Duration of anticoagulation was variable, with a median duration of 274 days (IQR, 101-2357) for outpatient therapeutic anticoagulation. Twelve of the 26 (46%) recurrent events occurred while anticoagulation was prescribed. ConclusionThe incidence rate of recurrent VTE in pediatric patients with a prior unprovoked VTE is high, particularly for adolescents and those with inherited thrombophilia. Therefore, future research should focus on the efficacy of prolonged anticoagulation for this population.

Pediatric Spontaneous Heparin-Induced Thrombocytopenia and Thrombosis Resulting in Thrombotic Storm

Background: The annual incidence of venous thromboembolism in pediatric patients is approximately 6 out of 1000 in the United States. In rare cases, rapid progression of multifocal thrombosis occurs despite therapeutic anticoagulation with heparin or low molecular weight heparin. Heparin-induced thrombocytopenia (HIT) is a pro-thrombotic disorder caused by an IgG-mediated immune response against platelet factor 4 resulting in platelet activation and risk of thrombosis, classically associated with prior exposure to heparin. The literature reports rare cases of adult patients developing HIT and thrombosis (HITT) without prior exposure. Objective: Aim to describe a case of spontaneous HITT in a pediatric patient which has never previously been published in the literature. Design/Method: Single subject case report developed with literature review. Results: 2-year-old male with no past medical history who presented with 5 days of frontal headaches and irritability. Neuroimaging, including CT, MRI, and MRV demonstrated extensive sinus venous thrombosis requiring initial anticoagulation with heparin. However, within 48 hours of initiation, the patient developed significant thrombocytopenia concerning for HIT. Lab testing was positive for both heparin-induced antibody and serotonin release assay, despite no prior heparin exposure. The remainder of the hypercoagulability workup was negative. Heparin was discontinued and the patient subsequently showed inadequate response to initial treatment with first-generation1 direct thrombin inhibitor (DTI) (Argatroban). Due to ongoing severe progressive symptomatic thrombocytopenia and thrombosis concerning for HIIT with thrombotic storm, the patient was treated with DTI (Bivalirubin), high dose methylprednisolone, and anti-CD20 therapy (Rituximab). This resulted in an improved clinical, laboratory, and neuroimaging response, and the patient was able to be gradually weaned off steroid therapy, and transitioned to anticoagulation with warfarin, with plans to remain on long-term anticoagulation. Conclusion: This is the first reported case in the literature of spontaneous HIIT in a pediatric patient. Spontaneous HITT is the primary explanation due to fulminant thrombosis and positive heparin-induced antibody and serotonin release assay with no prior heparin exposure, thrombocytopenia without immediate improvement upon heparin discontinuation, and blood smear showing normal red blood cell and platelet morphology. Spontaneous HIIT is a rare but important differential to consider in patients presenting with thrombosis and thrombocytopenia as the treatment differs from that of classic HIT, requiring heparin discontinuation, alternative anticoagulation, and immunomodulation.

Association of low serum albumin with venous thrombosis in pediatric patients

ObjectivesThe incidence of venous thromboembolism (VTE) in children is increasing, attributed in part to increased utilization of central venous catheters (CVCs). Children with protein losing disorders (PLDs) and low serum albumin may have an increased incidence of thrombosis. We sought to determine the prevalence of PLDs and hypoalbuminemia at the time of diagnosis of VTE in pediatric patients and its relationship to central venous catheters. MethodsWe performed a single institution retrospective study of 65 consecutive hospitalized pediatric patients with an acute VTE. Data collected included clinical diagnoses, type of thrombosis, presence or absence of a CVC, and serum albumin level, if available. ResultsOf 65 patients with acute VTE, 51 % (33/65) had catheter-related thrombosis (CRT), including 71 % (19/27) of patients <12 years of age and 37 % (14/38) of patients aged 12 to 23 (P = 0.008). Eleven VTEs occurred in patients with a diagnosis of a PLD; of these, ten (91 %) were CRT and one (9 %) was a non-CRT (P = 0.003). Serum albumin levels obtained within four days of diagnosis of VTE were available for 38 patients. An albumin level below the lower limit of the age-adjusted normal reference range was documented in 27/38 (71 %) patients with VTE compared to 1011/3028 (33 %) of all pediatric patients admitted to the hospital during a two-year period (P < 0.0001). Albumin levels were low in 19/22 (86 %) patients with CRT compared with 8/16 (50 %) patients with non-CRT (P = 0.019). ConclusionLow serum albumin levels are highly prevalent among pediatric patients with VTE, especially in those patients with CRT.

Dabigatran Etexilate: A Review in Pediatric Venous Thromboembolism

Although rare in children, venous thromboembolism (VTE) is markedly more likely in hospitalized patients, particularly with the use of central venous access devices. Dabigatran etexilate (Pradaxa®) is one of the first direct non-vitaminK antagonist oral anticoagulants (DOAC) approved for use in pediatric patients. It is approved in the EU and USA for the treatment of VTE in patients who have been treated with a parenteral anticoagulant for ≥ 5 days, and for the prevention of recurrent VTE. In an open-label, phase2b/3 clinical trial in pediatric patients with acute VTE treated for ≈ 3months, dabigatran etexilate was non-inferior to standard of care (SOC) treatment for the primary composite endpoint of complete thrombus resolution, freedom from recurrent VTE and VTE-related death. In a single-arm phase3 safety study, few patients experienced recurrent VTE with ≤ 12months of anticoagulation with dabigatran etexilate. Dabigatran etexilate was generally well tolerated in both studies; bleeding events were mostly minor and, in the phase 2b/3 study, occurred at a similar incidence to SOC. Although further data will be useful, dabigatran etexilate is a valuable and convenient treatment option in pediatric VTE.

Venous thromboembolism in pediatric patients with acute lymphoblastic leukemia under chemotherapy treatment. Risk factors and usefulness of thromboprophylaxis. Results of LAL‐SEHOP‐PETHEMA‐2013

IntroductionSymptomatic venous thromboembolism (VTE) is diagnosed in 3%–14% of patients during pediatric acute lymphoblastic leukemia (ALL) therapy. There are well‐known risk factors, but the role of others as inherited thrombophilia is still controversial. Prophylaxis with low molecular weight heparin (LMWH) has been described, but its use is not globally accepted. MethodsA retrospective multicentric study in ALL patients 1–18 years old following SEHOP‐PETHEMA‐2013 treatment guideline was performed to evaluate VTE rate, anticoagulant treatment, outcome, risk factors, and safety and usefulness of LMWH administration as primary thromboprophylaxis in children with inherited thrombophilia. ResultsA total of 652 patients were included in the study. VTE incidence was 8.7%. Most of the cases occurred during induction therapy associated with central venous catheter. Univariant analysis showed that family history of thrombosis, presence of mediastinal mass, high‐risk treatment group, and inherited thrombophilia were statistically significant risk factors. LMWH administration seemed to decrease VTE rate in patients with inherited thrombophilia and those with T‐cell ALL phenotype. ConclusionMost of the VTE cases occurred in patients without inherited thrombophilia, but when it is present, the VTE risk is higher. LMWH administration was useful to decrease VTE in these patients.

Venous thromboembolism in pediatric patients with sickle cell disease: A north American survey on experience and management approaches of pediatric hematologists

BackgroundThere is a lack of pediatric-specific data to guide recommendations for prevention and management of venous thromboembolism (VTE) in sickle cell disease (SCD). Experience and expert opinion in this area have not been reported. ObjectivesTo characterize the management practices of pediatric hematologists in SCD-associated VTE. We hypothesized there is substantial variability in duration of therapy and prophylaxis preferences. MethodsElectronic survey among pediatric hematologists members of three international subspecialty societies/consortia. ResultsAmong 52 complete respondents (response rate, 42%), 47% of physicians reported treating 1–2 patients with SCD-associated VTE, while 20% treated 3–5 patients during the preceding 12 months. Most respondents (86%) estimated the risk of VTE recurrence at <5%. The vast majority (98%) of respondents prescribed anticoagulation for symptomatic VTE treatment. Duration of therapy varied by VTE type, 95% reported prescribing 6 weeks-3 months for provoked DVT, while 60% reported prescribing a similar duration for provoked PE with the remaining 40% reporting treating PE for longer duration. There was notable variation in the treatment practices for asymptomatic or unprovoked VTE. Lastly, half of physicians indicated to be “somewhat” (40%) and “not at all” (10%) confident making decisions regarding the duration and intensity of prophylactic anticoagulation. ConclusionsWe identified significant variability in practice, a lower than expected perceived risk of recurrence, and uncertainty regarding VTE prophylaxis strategies in pediatric SCD. Cooperative multicenter studies are needed to generate evidence for future treatment guidelines development, and to identify opportunities for interventions aimed at managing and preventing VTE in pediatric SCD.

Duration of Anticoagulant Treatment for Acute Provoked Venous Thromboembolism in Pediatric Patients

Duration of Anticoagulant Treatment for Acute Provoked Venous Thromboembolism in Pediatric Patients

Association of venous thromboembolism following pediatric traumatic spinal injuries with injury severity and longer hospital stays.

Venous thromboembolism (VTE) can cause significant morbidity and mortality in hospitalized patients, and may disproportionately occur in patients with limited mobility following spinal trauma. The authors aimed to characterize the epidemiology and clinical predictors of VTE in pediatric patients following traumatic spinal injuries (TSIs). The authors conducted a retrospective cohort analysis of children who experienced TSI, including spinal fractures and spinal cord injuries, encoded within the National Trauma Data Bank from 2011 to 2014. Of the 22,752 pediatric patients with TSI, 192 (0.8%) experienced VTE during initial hospitalization. Proportionally, more patients in the VTE group (77%) than in the non-VTE group (68%) presented following a motor vehicle accident. Patients developing VTE had greater odds of presenting with moderate (adjusted odds ratio [aOR] 2.6, 95% confidence interval [CI] 1.4-4.8) or severe Glasgow Coma Scale scores (aOR 4.3, 95% CI 3.0-6.1), epidural hematoma (aOR 2.8, 95% CI 1.4-5.7), and concomitant abdominal (aOR 2.4, 95% CI 1.8-3.3) and/or lower extremity (aOR 1.5, 95% CI 1.1-2.0) injuries. They also had greater odds of being obese (aOR 2.9, 95% CI 1.6-5.5). Neither cervical, thoracic, nor lumbar spine injuries were significantly associated with VTE. However, involvement of more than one spinal level was predictive of VTE (aOR 1.3, 95% CI 1.0-1.7). Spinal cord injury at any level was also significantly associated with developing VTE (aOR 2.5, 95% CI 1.8-3.5). Patients with VTE stayed in the hospital an adjusted average of 19 days longer than non-VTE patients. They also had greater odds of discharge to a rehabilitative facility or home with rehabilitative services (aOR 2.6, 95% CI 1.8-3.6). VTE occurs in a low percentage of hospitalized pediatric patients with TSI. Injury severity is broadly associated with increased odds of developing VTE; specific risk factors include concomitant injuries such as cranial epidural hematoma, spinal cord injury, and lower extremity injury. Patients with VTE also require hospital-based and rehabilitative care at greater rates than other patients with TSI.

Direct Oral Anticoagulants: Overcoming the Challenges of Managing Venous Thromboembolism in Children

Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism, is relatively common among adults, with estimated incidence rates ranging from approximately 10 to 1200 per 100 000 adults aged ≥30 years. 1 Raskob G.E. Angchaisuksiri P. Blanco A.N. Büller H. Gallus A. Hunt B.J. et al. Thrombosis: a major contributor to global disease burden. Semin Thromb Hemost. 2014; 40: 724-735 Crossref PubMed Scopus (73) Google Scholar VTE is less common in children than in adults, with estimated incidence rates ranging from 0.7 to 4.9 per 100 000 children. 2 Andrew M. David M. Adams M. Ali K. Anderson R. Barnard D. et al. Venous thromboembolic complications (VTE) in children: first analyses of the Canadian Registry of VTE. Blood. 1994; 83: 1251-1257 Crossref PubMed Google Scholar , 3 van Ommen C.H. Heijboer H. Büller H.R. Hirasing R.A. Heijmans H.S. Peters M. Venous thromboembolism in childhood: a prospective two-year registry in The Netherlands. J Pediatr. 2001; 139: 676-681 Abstract Full Text Full Text PDF PubMed Scopus (517) Google Scholar , 4 Stein P.D. Kayali F. Olson R.E. Incidence of venous thromboembolism in infants and children: data from the National Hospital Discharge Survey. J Pediatr. 2004; 145: 563-565 Abstract Full Text Full Text PDF PubMed Scopus (237) Google Scholar , 5 Tuckuviene R. Christensen A.L. Helgestad J. Johnsen S.P. Kristensen S.R. Pediatric venous and arterial noncerebral thromboembolism in Denmark: a nationwide population-based study. J Pediatr. 2011; 159: 663-669 Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar However, it can have serious consequences, such as death, recurrence of thrombosis, loss of vessel patency required for future intravascular cannulation or organ transplantation, chronic pulmonary hypertension, or post-thrombotic syndrome. 2 Andrew M. David M. Adams M. Ali K. Anderson R. Barnard D. et al. Venous thromboembolic complications (VTE) in children: first analyses of the Canadian Registry of VTE. Blood. 1994; 83: 1251-1257 Crossref PubMed Google Scholar ,6 Goldenberg N.A. Donadini M.P. Kahn S.R. Crowther M. Kenet G. Nowak-Göttl U. et al. Post-thrombotic syndrome in children: a systematic review of frequency of occurrence, validity of outcome measures, and prognostic factors. Haematologica. 2010; 95: 1952-1959 Crossref PubMed Scopus (137) Google Scholar , 7 Greene L.A. Goldenberg N.A. Deep vein thrombosis: thrombolysis in the pediatric population. Semin Intervent Radiol. 2012; 29: 36-43 Crossref PubMed Scopus (18) Google Scholar , 8 Pelland-Marcotte M.C. Tucker C. Klaassen A. Avila M.L. Amid A. Amiri N. et al. Outcomes and risk factors of massive and submassive pulmonary embolism in children: a retrospective cohort study. Lancet Haematol. 2019; 6: e144-e153 Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar Despite its relative rarity, the incidence of pediatric VTE has increased in recent years. 5 Tuckuviene R. Christensen A.L. Helgestad J. Johnsen S.P. Kristensen S.R. Pediatric venous and arterial noncerebral thromboembolism in Denmark: a nationwide population-based study. J Pediatr. 2011; 159: 663-669 Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar ,9 Sandoval J.A. Sheehan M.P. Stonerock C.E. Shafique S. Rescorla F.J. Dalsing M.C. Incidence, risk factors, and treatment patterns for deep venous thrombosis in hospitalized children: an increasing population at risk. J Vasc Surg. 2008; 47: 837-843 Abstract Full Text Full Text PDF PubMed Scopus (127) Google Scholar ,10 Carpenter S.L. Richardson T. Hall M. Increasing rate of pulmonary embolism diagnosed in hospitalized children in the United States from 2001 to 2014. Blood Adv. 2018; 2: 1403-1408 Crossref PubMed Scopus (38) Google Scholar This increase is considered related to a number of factors, including the increased use of central venous catheters (CVCs), improved survival rates for children with chronic or critical conditions, and more frequent VTE diagnoses through improved pediatrician awareness and imaging techniques. 11 Raffini L. Huang Y.S. Witmer C. Feudtner C. Dramatic increase in venous thromboembolism in children's hospitals in the United States from 2001 to 2007. Pediatrics. 2009; 124: 1001-1008 Crossref PubMed Scopus (569) Google Scholar ,12 Malec L. Young G. Treatment of venous thromboembolism in pediatric patients. Front Pediatr. 2017; 5: 26 Crossref PubMed Scopus (18) Google Scholar First to the public, next to youThe Journal of PediatricsVol. 240PreviewThanks to direct-to-consumer marketing, snappy jingles, familiar spokespeople, and ubiquitous slogans, you are probably familiar with some direct oral anticoagulants (as well as any number of other classes of medications), such as rivaroxaban (Xarelto) and apixaban (Eliquis). You might not have focused on their use, however, since they were initially developed for use in adults. This volume of The Journal includes a Medical Progress report on direct anticoagulants (DOACs) for use in children with venous thromboembolism, including data from the latest trials and projected approval by the US Food and Drug Administration. Full-Text PDF

Venous Thromboembolism Risk and Thromboprophylaxis in Pediatric Neurosurgery and Spinal Injury: Current Trends and Literature Review

Although the entities of venous thromboembolism (VTE), deep venous thrombosis, pulmonary embolus, and thromboprophylaxis in adult patients undergoing brain tumor and spine surgery, traumatic brain injury and elective neurosurgical procedures are widely elucidated, the same is not valid when pediatric patients are under consideration. An attempt to review the peculiarities of these patients through a comprehensive bibliographic review is undertaken. We performed a narrative summary of the relevant literature dedicated to pediatric patients, centered on traumatic brain injury, the general incidence of thromboembolic disease in this patient population, the role of low molecular weight heparin (LMWH) in the treatment and prophylaxis of VTE, and its role in elective neurosurgical procedures, including spinal operations. Additionally, the risk of deep venous thrombosis in elective neurosurgical procedures is reviewed. Due to inherent limitations of the current studies, particularly a restricted number of patients, our data are underpowered to give a definitive protocol and guidelines for all the affected patients. Our current conclusions, based only on pediatric patients, argue that there is limited risk of VTE in pediatric patients suffering from brain tumors and that the possibility of VTE is very low in children undergoing elective neurosurgical procedures. There is no consensus regarding the exact incidence of VTE in traumatic brain injury patients. LMWH seems to be a safe and effective choice for the "at risk" pediatric patient population defined as being older than 15 years, venous catheterization, nonaccidental trauma, increased length of hospital stays, orthopaedic (including spinal) surgery, and cranial surgery.

The Trilogy of SARS-CoV-2 in Pediatrics (Part 3): Thrombosis, Anticoagulant, and Antiplatelet Considerations

The hypercoagulable state induced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects all patients regardless of age. The incidence of venous thromboembolism in pediatric patients with SARS-CoV-2-related illnesses is not well established. Although deep vein thrombosis is rare in children in the absence of risk factors, coagulopathy and the development of thromboses have been described in pediatric patients with acute COVID-19 and multisystem inflammatory syndrome. This comprehensive review provides a detailed overview of SARS-CoV-2-associated coagulopathy as well as strategies for optimizing the evaluation, management, and prevention of thrombosis in pediatric patients.

Unprovoked Versus Provoked Venous Thromboembolism in Pediatric Patients: Comparison of Characteristics and Outcomes

Background: The incidence of Venous thromboembolism (VTE) is increasing in the pediatric population which has led to a significant impact on morbidity, mortality and health care costs. The majority of VTE episodes diagnosed in children are considered provoked events secondary to an identifiable risk factor. In contrast, truly unprovoked VTE events are rare in children and there is limited data describing clinical course and outcomes in this population. The aim of this study is to highlight important differences in characteristics and outcomes of unprovoked VTE compared to provoked VTE in pediatric patients.Method: We performed a retrospective analysis of a prospectively maintained institutional thrombosis database. We identified all patients with an objectively confirmed VTE at our institution over a 5-year period from 2011 to 2016. Patients were managed according to standardized institutional protocols based on published guidelines. We compared patients with unprovoked VTE to those with provoked VTE with regards to demographics, prevalence of high risk thrombophilia (defined as inherited deficiency of antithrombin, protein C, or protein S, or antiphospholipid antibody syndrome), frequency of extensive VTE (defined as completely occlusive thrombosis involving >1 venous segment), frequency of pulmonary embolism (PE), frequency of recurrent VTE and frequency of post-thrombotic syndrome (PTS) assessed using the Manco-Johnson instrument in evaluable patients with history of VTE involving extremity veins, inferior vena cava, and/or superior vena cava. Data was compared using the Mann-Whitney U test or Fisher exact test as appropriate. Two-tailed p value less than 0.05 was considered statistically significant.Results: See Table 1 for a summary of the results. A total of 313 patients developed 336 VTE events at our institution during the study period. Of 336 VTE events, 24 (7%) were unprovoked events affecting 19 patients. Patients with unprovoked VTE were significantly older compared to patients with provoked VTE while gender distribution was similar between the 2 groups. The prevalence of high risk thrombophilia was significantly higher in patients with unprovoked VTE. Similarly, the frequencies of extensive VTE, PE and recurrent VTE were significantly higher in patients with unprovoked VTE. The frequency of physically and functionally significant PTS was not significantly different between the two groups. However, the frequency of PTS of any severity was significantly higher in patients with unprovoked VTE.Conclusion: Our study indicates that pediatric patients with unprovoked VTE represent a distinct patient population that appears to be at high risk for poor outcomes. Multicenter, prospective studies are needed to confirm our results and for developing optimal evidence-based risk stratified treatment approaches. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Venous Thromboembolism After Pelvic Osteotomy in Adolescent Patients: A Database Study Characterizing Rates and Current Practices.

Current risks and practices in medical prophylaxis of venous thromboembolism (VTE) after major elective lower extremity surgeries such as pelvic osteotomies have not been well-defined in the pediatric population. The purpose of this study was to (1) evaluate population rates of VTE in adolescents undergoing pelvic osteotomies, and (2) characterize current practices on types of VTE prophylaxis being utilized after pelvic osteotomies. The study evaluated the Pediatric Health Information System database between October 1, 2015 and January 1, 2020 for patients between 10 and 18 years of age meeting selected ICD-10 procedure and diagnosis codes relating to pelvic osteotomies. The rate of VTE was calculated within 90 days of index procedure. Types of pharmacologic prophylaxis were characterized. Continuous variables were compared with 2-sample t tests; proportions and categorical variables were compared with Fisher exact or χ2 tests, all with 2-tailed significance <0.05. Of 1480 included patients, 9 were diagnosed with VTE within 90 days of surgery (VTE rate: 0.61%). Four of 9 (44.4%) had received pharmacologic prophylaxis postoperatively. There were no differences in baseline demographics or length of stay between patients that did or did not develop VTE (P>0.05). Overall, 52.0% received at least one form of pharmacologic prophylaxis postoperatively. The most common pharmacologic prophylaxis used was aspirin (47.6%), of which 64.4% received 81 mg dosing. There was no difference in VTE rates in those with or without prophylaxis (0.52% vs. 0.70%, P=0.75). However, those prescribed prophylaxis were significantly older (15.2±2.3 vs. 13.6±2.4 y, P<0.0001) and had a higher proportion of females (71.8% vs. 54.6%, P<0.01). The overall rate of VTE in pediatric patients after pelvic osteotomies is non-negligible. There is heterogeneity in the type of anticoagulant utilized; however, VTE prophylaxis is most commonly prescribed in older adolescents and female patients. Guidelines for medical prevention of deep venous thrombosis and pulmonary embolism in the pediatric population are warranted after hip preservation surgery. Level IV, case series.