Risk Of Thrombosis In Children Research Articles

Inherited Thrombophilia and Risk of Thrombosis in Children with Cancer: a Single-center Experience.

Thrombosis is an increasingly recognized complication of childhood malignancy and its treatment. The incidence and etiology of pediatric cancer-related thrombosis is still not well understood. The aim of this study was to evaluate the prevalence of common prothrombotic genetic conditions in children with cancer, the frequency of thrombosis, and the role of inherited thrombophilia in the development of thrombosis in a pediatric oncology population. Forty-seven children (36 treated for hematological malignancies and 11 for solid tumors) with a median age of 8.8. years (range 0.4 - 19.3 years) were included in the study. Genetic polymorphisms of Factor V Leiden (G1691A), prothrombin G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T were determined by real-time polymerase chain reaction-based DNA analysis. Four (8.5%) patients were heterozygous for Factor V Leiden, 3 (6.4%) were heterozygous for prothrombin G20210A mutation, and 3 (6.4%) were homozygous for MTHFR C677T mutation. All patients had implanted central venous catheters. Four (8.5%) children had documented thrombosis, three of which were in the upper venous system. Two of the four patients with thrombosis had Factor V Leiden heterozygosity. Thrombosis is an important complication of childhood cancer. The risk of thrombosis may be increased in patients with Factor V Leiden. In the absence of consensus guidelines, our results support the recommendation for thrombophilia screening in children with cancer.

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.

Factors Associated with the Development of Thrombosis in Pediatric Behçet Disease.

The present study aimed to compare the demographic, clinical, and laboratory characteristics of patients with pediatric Behçet disease (BD) with and without thrombosis to elucidate the factors that may contribute to the development of thrombosis. This observational, descriptive, medical records review study included patients with BD (n = 85) who were diagnosed at age younger than 16 years at our clinic between 2010 and 2022. The demographic, clinical, and available laboratory data of patients with and without thrombosis were compared. The potential risk factors for the development of thrombosis were evaluated with multivariable logistic regression analysis. Central venous sinus thrombosis was the most common type of thrombosis. Thrombosis was significantly more common in male patients ( p = 0.002), and regression analysis revealed that being male was a risk factor for developing thrombosis. Genital ulcers were less common in patients with thromboses. Patients with thrombosis had higher erythrocyte sedimentation rates, C-reactive protein, leukocyte, and neutrophil counts, as well as antinuclear antibody positivity. In contrast, mean platelet volume and lymphocyte counts were significantly lower in patients with thrombosis. According to the logistic regression analysis, erythrocyte sedimentation rate value >17 mm/h was a risk factor for developing thrombosis (odds ratio, 1; confidence interval, 1.1-1.8; p = 0.012). Male sex has been associated with an increased risk of thrombosis in children with BD. Inflammatory parameters may serve as predictive factors for thrombosis in pediatric BD.

PO-674-04 ANTICOAGULATION MANAGEMENT AND RISK OF THROMBOEMBOLISM IN HEALTHY YOUTH WITH ATRIAL FIBRILLATION: DATA FROM A MULTI-INSTITUTIONAL PACES COLLABORATIVE REGISTRY

Stroke is a well-defined complication of atrial fibrillation (AF) in adults. However, the risk of thromboembolism and need for anticoagulation therapy in children and young adults with AF are unknown. To describe the current anticoagulation practice and assess the risk of thrombosis in children and young adults with AF across 13 pediatric heart centers. Data was obtained from the multi-institutional PACES collaborative registry on atrial fibrillation. Patients ≤ 21 years of age with documented AF of an unknown cause from January 2004 to December 2018 were included. We included patients with AF with no structural heart disease, cardiomyopathy, ventricular pre-excitation, history of open heart surgery, hypertension, or thyroid disease. Of 241 subjects, 76 were prescribed oral anticoagulation at diagnosis and an additional 15 at time of AF recurrence. Aspirin was prescribed in 66 (73%) patients, warfarin in 14 (15%), novel oral anticoagulant in 7 (8%), combined therapy in 3 (3%), and unknown in 1 (1%). In a multivariable model, patients were less likely to be anticoagulated at a freestanding children’s hospital (OR 0.44, 95%CI [0.23-0.78], p=0.005) or if they had spontaneous cardioversion (OR 0.53, 95%CI [0.29-0.96], p=0.037), and more likely if prescribed an antiarrhythmic at time of initial diagnosis (OR 1.82, 95%CI [1.01-3.3], p=0.047). There was a trend towards anticoagulation in patients presenting with asymptomatic AF (OR 0.45, 95%CI [0.19-1.03], p=0.06]). Age at diagnosis, gender, and BMI were not associated with anticoagulation status. One patient (1/241, 0.4%) was found to have left atrial thrombus confirmed by transesophageal echocardiogram at time of presentation. This patient was treated with warfarin for 3 months and repeat echocardiogram showed thrombus resolution. No patient developed thromboembolic phenomenon over a mean follow up of 2.1 ± 2.6 years. Our study is the first to demonstrate that there is large practice variation in anticoagulation management with patients treated at a free-standing children’s hospital being less likely to be anticoagulated. AF associated thrombosis is rare in children and young adults.

PB2426 CLINICAL MANIFESTATION OF HEREDITARY THROMBOPHILIA IN CHILDREN

Background:Venous thromboembolism (VTE) in children is becoming a more frequent problem. The pathogenesis of thrombosis is complex: thrombophilia, background disease, trigger factor. Special attention should be deserved to hereditary thrombophilia (HT), which from childhood can be accompanied by persistent disorders in the hemostasis system and significantly increase the risk of thrombosis.Aims:To assess the influence of HT on the development of venous thromboembolic complications in children.Methods:We have examined 24 patients aged from 1 day to 18 years, who had various types of thrombotic manifestations (n = 20) or the threat thereof taking into account the family history (n = 4). The average age of children was 5.6 years, the ratio of girls to boys was 1.4 / 1.0. All patients underwent a full laboratory examination aimed at the diagnosis of HT and antiphospholipid syndrome (APS): levels of antithrombin III (ATIII), protein C and S, antibodies to β2‐glycoprotein and cardiolipin, lupus anticoagulant, homocysteine level. Molecular genetic testing included thrombogenic mutations and polymorphisms.Results:In half of the cases of VTE, the lower extremity deep vein thrombosis of was diagnosed. Venous sinus thrombosis ‐ in 20% of the examined (n = 4); pulmonary artery thromboembolism in one case; thrombosis in the pool of the portal and superior vena cava ‐ in 35%. VTE recurrences were observed in 20% of cases. The diagnosis of HT is verified in 62.5% of all examined children and in 55% of children with thrombosis. The HT variants were distributed in the following way: 33.3% ‐ mutation in the FV Leiden (het) gene; 20% ‐ in the prothrombin G20210A (het) gene; AT III deficiency was diagnosed in three patients (20%); combined mutations in MTHFRC‐677T (T/T) and PAI‐1 (4G/4G) genes‐ 26.7%. MTHFRC‐677T (T/T) mutations in two cases were accompanied by moderate hyperhomocysteinemia. Trigger factors for VTE not associated with HT were background diseases and its associated complications: acute lymphoblastic leukemia (n = 4); parenteral nutrition (n = 1); operative interventions (n = 2); autoimmune diseases (n = 2) and APS (n = 1). Clinical manifestation of HT in 63.3% of cases was observed in patients over 10 years old. In 72.7% of cases, VTE occurred spontaneously. The earliest spontaneous VTE was detected in a child at the age of 1 day (portal vein thrombosis). In 75% of cases of recurrent VTE, HT has occurred.Summary/Conclusion:Hereditary thrombophilia is a sign of the potential risk of thrombosis in children. Clinical manifestation of VTE occurs at any location, at any age, but significantly more often in children older than 10 years. The presence of HT is a high risk factor for recurrent and spontaneous VTE. Diagnosis of HT is reasonable to carry out in all cases of VTE in children, which is important not only for assessment of the risk of repeated thrombotic episodes, but also for selecting the antithrombotic therapy regimen and optimizing preventive measures.

Analysis of Patient Characteristics and Risk Factors for Thrombosis After Surgery for Congenital Heart Disease.

Thrombosis is a cause of morbidity in 4-15% of children who undergo pediatric cardiac surgery. Data on how to prevent this complication are sorely needed. We aimed to identify risk factors for thrombosis following pediatric cardiac surgery and determine if use of low molecular weight heparin prophylaxis is associated with a reduction in thrombosis risk. Retrospective cohort study. Tertiary pediatric cardiovascular ICU. Patients who underwent cardiac surgery between June 2014 and December 2015. None. Data from patients with venous or arterial thrombosis confirmed by radiologic studies were matched two-to-one to controls based on age, Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery mortality category, and gender. Thrombosis was detected in 33 patients (6.2%): 25 patients (76%) had venous thromboses, five patients (15%) had arterial thromboses, and three patients (9%) had both. Median time to thrombosis detection was 13 days (25-75%; 7-31 d). On multivariate analysis, which included adjustment for postoperative disease severity, fresh frozen plasma exposure was independently associated with thrombosis (odds ratio, 3.7; 95% CI, 1.4-9.4). Twenty-eight patients (85%) had central venous catheter-related thromboses. Low molecular weight heparin prophylaxis use in this subset of patients was not statistically different from controls (50% vs 45%, respectively; p = 0.47). On multivariable analysis, fresh frozen plasma exposure was also independently associated with central venous catheter-related thrombosis (odds ratio, 3.6; 95% CI, 1.2-10.6). The occurrence of thrombosis after pediatric cardiac surgery at our institution was 6.2%, similar to what has been reported in other studies, despite frequent use of low molecular weight heparin. Further study is needed to determine the role of low molecular weight heparin for thromboprophylaxis and the relationship between fresh frozen plasma and thrombosis risk in children who undergo cardiac surgery.

Impact of baseline clinical and laboratory features on the risk of thrombosis in children with acute lymphoblastic leukemia: A prospective evaluation.

Children with acute lymphoblastic leukemia (ALL) have increased risk of thromboembolism (TE). However, the predictors of ALL-associated TE are as yet uncertain. This exploratory, prospective cohort study evaluated the effects of clinical (age, gender, ALL risk group) and laboratory variables (hematological parameters, ABO blood group, inherited and acquired prothrombotic defects [PDs]) at diagnosis on the development of symptomatic TE (sTE) in children (aged 1 to ≤18) treated on the Dana-Farber Cancer Institute ALL 05-001 study. Samples collected prior to the start of ALL therapy were evaluated for genetic and acquired PDs (proteins C and S, antithrombin, procoagulant factors VIII (FVIII:C), IX, XI and von Willebrand factor antigen levels, gene polymorphisms of factor V G1691A, prothrombin gene G20210A and methylene tetrahydrofolate reductase C677T, anticardiolipin antibodies, fasting lipoprotein(a), and homocysteine). Of 131 enrolled patients (mean age [range] 6.4 [1-17] years) 70 were male patients and 20 patients (15%) developed sTE. Acquired or inherited PD had no impact on the risk of sTE. Multivariable analyses identified older age (odds ratio [OR] 1.13; 95% confidence interval [CI]: 1.01, 1.26) and non-O blood group (OR 3.64, 95% CI: 1.06, 12.51) as independent predictors for development of sTE. Patients with circulating blasts had higher odds of developing sTE (OR 6.66; 95% CI: 0.82, 53.85). Older age, non-O blood group, and presence of circulating blasts, but not PDs, predicted the risk of sTE during ALL therapy. We recommend evaluation of these novel risk factors in the development of ALL-associated TE. If confirmed, these easily accessible variables at diagnosis can help develop a risk-prediction model for ALL-associated TE.

Alterations in Procoagulant, Anticoagulant, and Fibrinolytic Systems Before and After Start of Induction Chemotherapy in Children With Acute Lymphoblastic Leukemia

Induction chemotherapy is associated with increased thrombosis risk in children with acute lymphoblastic leukemia (ALL). In this prospective study, we explored the effects of ALL and induction chemotherapy on the procoagulant, anticoagulant, and fibrinolytic systems in 20 children with ALL. The levels of d-dimer, factor VIII, von Willebrand factor, protein C, antithrombin III, and thrombin-activated fibrinolysis inhibitor (TAFI) were elevated at diagnosis. These changes were not related with peripheral blast count. The levels of fibrinogen, d-dimer, coagulation inhibitors, and plasminogen decreased, whereas the levels of tissue factor pathway inhibitor and plasminogen activator inhibitor 1 increased progressively following prednisolone monotherapy, administration of vincristine plus daunorubicin, and l-asparaginase. The levels of factor VIII, d-dimer, and TAFI remained elevated during the study period. In conclusion, coagulation activation and impaired fibrinolysis already exist at diagnosis, whereas induction chemotherapy leads to reactivation of coagulation and progressive impairment in fibrinolytic and anticoagulant capacities in childhood ALL.

Pediatric Behçet’s Disease and Thromboses

To describe the characteristics of a group of pediatric patients with Behçet's disease (BD) who presented at least 1 episode of thrombosis during their disease course. We made a retrospective chart review of the clinical, biological, and radiological data of children with BD who presented at least 1 episode of either arterial or venous thrombosis. Data were extracted from both an international pediatric Behçet cohort and files referred from 7 French centers. Twenty-one patients were included. Diagnosis of BD was based on the criteria of the International Study Group for BD. Main locations for thrombosis were the cerebral sinuses, in 11 patients (52.4%); and lower limbs, in 9 patients (40.9%). Recurrent episodes were observed in 4 patients (21%). Thrombophilia measurements were normal in 14 patients out of 21, while anticardiolipin antibodies were positive in 4 patients, and 2 out of 21 had protein C deficiency. One patient had lupus anticoagulant. All patients were treated with colchicine. Corticosteroids were also added for variable periods in 13 patients. Five patients out of 21 were treated with anticoagulants (heparin, then anti-vitamin K) and 3 with antiplatelets (acetylsalicylic acid). Thromboses are a serious complication of BD and may occur early in the disease course. The presence of thrombophilic markers could increase the risk of thrombosis in BD, but the size of our population does not allow any conclusion. An international cohort (PED-BD) is currently in place and will allow study of such cases longitudinally, as well as assessment of the elements that correlate with an increased risk of thrombosis in children with BD.

Treatment of endothelium with the chemotherapy agent vincristine affects activated protein C generation to a greater degree in newborn plasma than in adult plasma

Introduction Activated protein C (APC) is well-established as a physiologically important anticoagulant. During development, plasma concentrations of protein C and α 2macroglobulin, factors involved in APC generation, differ from adult levels. Chemotherapy drugs can perturb endothelial expression of PC-activating receptors. This study examines the effect of chemotherapy treatment of endothelium on APC generation in newborn and adult plasma. Materials and methods APC generations were initiated on endothelial cells treated with vincristine or media by recalcifying defibrinated plasma with buffer containing thromboplastin. APC generation was terminated by mixing timed subsamples into FFRCMK-EDTA or heparin, followed by EDTA. APC-PCI and APC-α 1AT were assayed by ELISA. APC-α 2M was measured chromogenically. Since heparin converts free APC to APC-PCI, the difference between APC-PCI detected in heparin subsamples and APC-PCI detected in FFRCMK-EDTA subsamples gave the free APC. Cellular expression of EPCR and TM were measured by flow cytometry and Western blot. Results Vincristine-treated endothelium decreased free APC generation in newborn plasma to a greater degree than in adult plasma. APC-PCI levels in both adult and newborn plasma were unaffected by chemotherapy. Vincristine treatment reduced levels of APC-α 1 AT and APC-α 2 M to a greater degree in newborn plasma versus adult plasma. Expression of EPCR was reduced in cells treated with vincristine. Conversely, TM was reduced on the cell surface, but increased in whole cell lysates. Conclusions The differential response of newborn and adult plasma PC components to chemotherapy-mediated changes in cell surface components may be a factor in the increased risk of thrombosis in children receiving chemotherapy.

Laboratory markers of thrombosis risk in children with hereditary spherocytosis

Recent data suggest that adults with hereditary spherocytosis (HS) may be protected from atherothrombosis before splenectomy but have increased risk of thrombosis following splenectomy. In order to aid in making informed decisions regarding splenectomy in children with HS, we conducted a retrospective study of several surrogate laboratory markers of thrombosis risk in children with HS. A retrospective record review was performed on 246 children with HS. Platelet count and hemoglobin concentration were recorded prior to and following splenectomy in each patient. Serum cholesterol levels were collected from the record when available. Prior to splenectomy, hypocholesterolemia was common. Mean platelet counts in 31 evaluable patients pre- and post-splenectomy were 334 and 608 x 10(9)/L, respectively (P < 0.001). Twenty-nine patients (94%) exhibited persistent thrombocytosis following splenectomy. Hemoglobin values following splenectomy often rose to higher than age and gender-matched norms, with 30% of measurements greater than the 90th percentile and 17% greater than the 97th percentile. The findings of hypocholesterolemia before splenectomy and thrombocytosis and mild polycythemia afterwards support the hypothesis that patients with HS might be protected from thrombosis before splenectomy and/or more susceptible afterwards. Prospective studies of additional prothrombotic biomarkers and thrombotic events in HS patients are warranted.

Thrombotic complications in childhood acute lymphoblastic leukemia: a meta-analysis of 17 prospective studies comprising 1752 pediatric patients

AbstractThe risk of thrombosis in children with acute lymphoblastic leukemia (ALL) reportedly ranges between 1% and 37%. Epidemiologic studies have usually been hampered by small numbers, making accurate estimates of thrombosis risk in ALL patients very difficult. The aim of this study was to better estimate the frequency of this complication and to define how the disease, its treatment, and the host contribute to its occurrence. We made an attempt to combine and analyze all published data on the association between pediatric ALL and thrombosis, by using a meta-analytic method. The rate of thrombosis in 1752 children from 17 prospective studies was 5.2% (95% CI: 4.2-6.4). The risk varies depending on several factors. Most of the events occurred during the induction phase of therapy. Lower doses of asparaginase (ASP) for long periods were associated with the highest incidence of thrombosis, as were anthracyclines and prednisone (instead of dexamethasone). The presence of central lines and of thrombophilic genetic abnormalities also appeared to be frequently associated with thrombosis. In conclusion, the overall thrombotic risk in ALL children was significant, and the subgroup analysis was able to identify high-risk individuals, a finding that will hopefully guide future prospective studies aimed at decreasing this risk.

Factor VIII levels in children with thrombosis.

A number of coagulation defects have been implicated as risk factors in thrombo-embolic disease. Of these, high levels of clotting factor VIII have been shown to be associated with a five- to six-fold increased risk of thrombosis, compared to levels < 100 IU/dL in adults. The objective of this study was to investigate the prevalence of elevated plasma levels of factor VIII in a pediatric population with thrombo-embolism (TE). Forty-two children (17 female, 25 male) with TE and 165 healthy controls without familial history of thrombosis or stroke were included in the present study. Doppler ultrasonography with or without angiography, computed tomography, magnetic resonance imaging or echocardiography was utilized to establish the diagnosis. One-stage clotting assay with factor VIII-deficient plasma for measurement of factor VIII and immunoturbidometric assay for von Willebrand factor (vWF) levels were utilized. All measurements were performed in duplicate. Plasma levels of factor VIII were assessed in parents of nine patients to establish whether high levels of factor VIII were genetically determined. The median age at onset of TE was 7 years (range 0-17 years). Among patients with TE compared to controls, the prevalence of high factor VIII levels was 59.5% versus 12.1% (odds ratio 10.6, 95% CI: 4.9-23.1). The prevalence of high factor VIII levels was detected in at least one of nine families. The data in the present study provide evidence that elevated plasma factor VIII levels are associated with increased risk of thrombosis in children: thus, plasma concentration of factor VIII should be measured in all children with TE.

Thromboembolism in children

Acquired and inherited prothrombotic risk factors increase the risk of thrombosis in children. This review is based on "milestone" pediatric reports and new literature data (January 2001-February 2002) on the presence of acquired and inherited prothrombotic risk factors, imaging methods, and treatment modalities in pediatric thromboembolism. After confirming clinically suspected thromboembolism with suitable imaging methods, pediatric patients should be screened for common gene mutations (factor V G1691A, prothrombin G20210A and MTHFR C677T genotypes), rare genetic deficiencies (protein C, protein S, antithrombin, and plasminogen), and new candidates for genetic thrombophilia causing elevated levels of lipoprotein(a), and homocysteine, and probable genetic risk factors (elevations in fibrinogen, factor IX, and factor VIIIC, and decreases in factor XII). Data interpretation is based on age-dependent reference ranges or the identification of causative gene mutations/polymorphisms with respect to individual ethnic backgrounds. Pediatric treatment protocols for acute thromboembolism, including thrombolytic and anticoagulant therapy, are mainly adapted from adult patient protocols.

Morphologic and biochemical features affecting the antithrombotic properties of the inferior vena cava of rabbit pups and adult rabbits.

The incidence of venous thromboembolic disease is reduced in children compared with adults. Thromboprotective mechanisms, some of which have already been identified in plasma, must be present in children. Blood vessel walls have important antithrombotic properties that maintain blood fluidity. This is in part due to proteoglycan (PG)-related glycosaminoglycan (GAG) molecules within vessel walls. PGs are macromolecules with covalently attached GAG chains, either chondroitin, dermatan, heparan, or keratan sulfate. The influence of age on the concentration and anticoagulant activities of PGs and GAGs, within vein walls before puberty has not been previously investigated. We hypothesized that developmental differences in vein walls may contribute to the reduced risk of thrombosis in children. We used a rabbit model to examine morphologic and biochemical features of inferior venae cavae (IVCs). We assessed IVC wall morphology, PG distribution, GAG mass, and GAG antithrombin activity. Morphologically, there were only minor differences between pups and adult rabbits' IVCs. However, there was a significant increase in GAGs by mass in IVCs from pups compared with adult rabbits (p = 0.012). In addition the total antithrombin activity (p = 0.04), and especially that of heparan sulfate (p = 0.01) was significantly increased in pups compared with adult rabbits. These results demonstrate important differences in the antithrombotic properties of IVC walls in pups and adult rabbits. In summary, developmental differences in vein wall PG content and activity exist which may contribute to the reduced risk of venous thromboembolism in children. Further characterization of these differences is required.

Diagnosis of thromboembolic disease during infancy and childhood.

Thromboembolic disorders are frequent complications in pediatric patients and the incidence seems to rise. Adult guidelines for thromboembolism do not hold for children because there are many age-related features. Congenital prethrombotic disorders play a major role in the pediatric population and activated protein C (APC) resistance is also the most frequently encountered problem. Acquired risk factors in children are central venous line thrombosis with serious complications, cardiac diseases such as cardiomyopathies, prosthetic heart valves and aneurysms, renal vein thrombosis, and nephrotic syndrome. Renal vein thrombosis primarily affects newborns. Children with the antiphospholipid antibody syndrome also have thromboses although less frequent than adults, but systemic lupus erythematosus is associated with a high incidence. Acute lymphoblastic leukemia is frequently associated with thrombosis in children, especially when complicated by APC resistance. The greatest risk of thrombosis in children is during the neonatal period, and again congenital prethrombotic states and catheter placement play a major role. The clinical manifestations in children reflect the site of the thrombosis and extensive laboratory evaluations and advanced diagnostic procedures must be employed to diagnose the thrombotic events.