Thrombosis In Newborn Research Articles

Clinical case of successful thrombolysis in a newborn with thrombosis of the left renal vein

Thrombosis occurring in the neonatal period is a nosology with a large number of complications, often leading to disability and death. This article highlights the successful treatment of a newborn child with renal vein thrombosis using systemic thrombolysis. A clinical case of successful systemic thrombolysis in a full-term boy in the early neonatal period with thrombosis of the left renal vein and transition of the floating part of the thrombus to the inferior vena cava is presented. A child aged 3 days was admitted to the neonatal intensive care unit from a maternity hospital, where thrombosis was suspected. Gross hematuria was observed. Laboratory data revealed thrombocytopenia and increased levels of fibrinogen and D-dimer. Ultrasound showed a sharp increase in the volume of the left kidney, a diffuse change in its parenchyma, a sharp depletion of blood flow, and accumulation of fluid in the perinephric tissue on the left, and a thrombus was observed in the lumen of the left renal vein with the presence of a floating part extending into the inferior vena cava. Thrombolytic therapy with the drug alteplase was started in combination with an infusion of unfractionated heparin. Doses were selected based on coagulogram parameters. On day 2 of therapy, hematuria resolved. On day 4 of therapy, the alteplase infusion was completed, and heparin therapy was continued. On day 13, the child was switched to a low-molecular-weight-heparin therapy. Dynamic ultrasound revealed size reduction, recanalization and further thrombus lysis, and normalization of intrarenal blood flow and kidney size. No renal dysfunction was recorded during observation. The child was transferred to the further care unit at aged 14 days and was discharged home at the age of 25 days in satisfactory condition on ongoing anticoagulant therapy under outpatient supervision of a hematologist. During follow-up observation at aged 1.5 months of life, no clinical, laboratory, and ultrasound indicators of renal function disorders were noted. Currently, there are no approved recommendations and protocols for individual thrombosis in newborns, although this particular age group is due to the vulnerability of hemostasis to the development of a thrombotic process.

Deep Medullary Vein Thrombosis in Newborns: A Case Series and a Comparative Analysis of the Literature

Deep Medullary Vein Thrombosis in Newborns: A Case Series and a Comparative Analysis of the Literature

Renální vaskulární trombóza u novorozence - 1. část

Renální vaskulární trombóza u novorozence - 1. část

Renální vaskulární trombóza u novorozence - 2. část

Renální vaskulární trombóza u novorozence - 2. část

Features of hereditary thrombosis (analysis of clinical cases in newborns)

Background. Dysfunctions of hemostasis include conditions occurring both with hemorrhagic syndrome and in the form of thrombosis, the number of which is growing due to the intensification of the therapy. The relevance of the topic is determined by the prevalence of these pathological conditions in newborns, the peculiarities of the hemostasis system in the neonatal period, as well as the difficulties of diagnosis and interpretation of laboratory parameters.
 Aim. Studying the features of clinical manifestations and genetic markers in newborns with clinical thrombosis on the background of primary thrombophilia.
 Materials and methods. A retrospective continuous analysis of the case histories of newborn children with thrombophilia who were hospitalized at the Krasnoyarsk Regional Clinical Center for Maternity and Childhood Protection in the period from January 2014 to January 2020 was carried out.
 Results. The debut of thrombosis in newborns is represented mainly by venous thrombosis of various localizations. Genetic mutations were identified in these patients, which are mainly associated with the work of the folate and methionine cycles (MTHFR: g.677CT, MTHFR: g.1298AC, MTRR: g.66AG and MTR: g.2756AG). A complicated course was noted in the presence in the genome of the combinations MTHFR: g.677CT, MTR: g.2756AG and MTRR: g.66AG and/or homozygous carriage of MTHFR: g.677CT, MTHFR: g.1298AC. The main trigger was peripheral vascular catheterization.
 Conclusion. A decrease in the levels of natural anticoagulants in newborns with some physiological features of hemostasis deserves close attention of neonatologists and clinicians, requires an integral assessment of the hemostasis system and additional examinations, including the analysis of genetic changes not only in the hemostasis system, but also in folate and methionine cycles.

Vena Cava Thrombosis after Congenital Diaphragmatic Hernia Repair: Multivariate Analysis of Potential Risk Factors.

The treatment of newborns with congenital diaphragmatic hernia (CDH) is associated with a significant complication rate. Information on major thrombotic complications and their incidence in newborns with CDH is lacking. The aims of our analysis were to evaluate the frequency of vena cava thrombosis and to determine its predictors within a consecutive series of patients with CDH. We retrospectively analyzed charts of all neonates of our department that underwent CDH repair from 2007 to 2021, focusing on vena cava thrombosis. Vena cava thrombosis was diagnosed sonographically and classified as complete or partial venous occlusion. Complete occlusion was confirmed by cavography. Variables evaluated were CDH side, liver position, central vein line, surgical approach, and extracorporeal membrane oxygenation (ECMO). Univariate and multivariate tests were utilized. Among 57 neonates who underwent CDH repair, vena cava thrombosis was diagnosed in 14 (24.6%), seven of whom had complete occlusion of the vena cava. Factors associated with vena cava thrombosis were femoral or saphenous venous catheter (p = 0.044), right sided CDH (p = 0.027) and chylothorax (p < 0.0001). ECMO was not associated with vena cava thrombosis. Seven patients (50%) with vena cava thrombosis were treated interventionally with angioplasty and seven (50%) conservatively with anticoagulation only. Mortality was not higher in patients with compared with patients without vena cava thrombosis. The incidence of vena cava thrombosis in newborns with CDH in our series is high. Routine postoperative abdominal sonography focusing on vena cava thrombosis is mandatory in all patients with CDH. Patients who developed vena cava thrombosis were more likely to develop chylothorax after CDH repair. Considering the good outcome of medical therapy of partial vena cava thrombosis, it may be discussed whether low dose anticoagulation may be provided to all newborns with CDH.

Association of Gene Variants of Plasmic (&lt;i&gt;FGB&lt;/i&gt; -455 G&gt;A (rs1800790), &lt;i&gt;F2&lt;/i&gt; 20210 G&gt;A (rs1799963), &lt;i&gt;F5&lt;/i&gt; 1691 G&gt;A (rs6025), &lt;i&gt;F7&lt;/i&gt; 10976 G&gt;A (rs6046), &lt;i&gt;F13&lt;/i&gt; G&gt;T (rs5985)), Thrombocytic (&lt;i&gt;ITGA2&lt;/i&gt; 807 C&gt;T (rs1126643), &lt;i&gt;ITGB3&lt;/i&gt; 1565 T&gt;C (rs5918)), Fibrinolytic (&lt;i&gt;PAI-1&lt;/i&gt; -675 5G&gt;4G (rs1799889)) Hemostasis Components with Arterial or Venous Thrombosis in Newborns: Case-Controlled Study

Background. The severity of thrombosis clinical course, poor prognosis, upcoming disability and permanent organ failure in newborns necessitate further search and study of thrombotic conditions predictors in order to prevent them. Aim of the study is to analyze the frequency of gene variants of plasmic, thrombocytic and fibrinolytic hemostasis components and determine their role in the thrombosis development in newborn children. Methods. The study included 46 full-term newborns with thromboses of different localization – cases group. Inclusion criteria were: child age 28 days or less, gestational period &gt;37 weeks, informed consent on participation in the study. The control group included children of I and II health groups. Vascular thrombosis was diagnosed via instrumental imaging methods: vascular ultrasound, computer tomography, magnetic resonance imaging. Thrombophilic anamnesis and pregnant woman’s health condition was analyzed according to pregnancy medical records. The molecular genetic testing included 8 single nucleotide polymorphisms definition of the following genes: FGB -455 G&gt;A (rs1800790), F2 20210 G&gt;A (rs1799963), F5 1691 G&gt;A (rs6025), F7 10976 G&gt;A (rs6046), F13 G&gt;T (rs5985), ITGA2 807 C&gt;T (rs1126643), ITGB3 1565 T&gt;C (rs5918), PAI-1 -675 5G&gt;4G (rs1799889). Results. Molecular genetic predictors of thrombosis in newborns have been revealed: variants of fibrinogen gene FGB -455 G&gt;А (AP, %=66), plasminogen activator inhibitor gene PAI-1 -675 4G &gt; 4G (AP, % = 89), genotype associations PAI-1 -675 4G/&gt;4G /F7 10976 G&gt;G (AP, % = 82), PAI-1 -675 4G&gt;4G / F13 34 G&gt;G (AP, % = 63)PAI-1 -675 4G&gt;4G / F7 10976 G&gt;G / F13 34 G&gt;G(AP, % = 61), and integrin alpha 2 gene ITGA2 807 T/T (AP, % = 93). Maternal factor of thrombosis development in children is impaired uteroplacental circulation in pregnant woman (AP, % = 66). Conclusion. The role of gene variants of plasmic, thrombocytic and fibrinolytic hemostasis components in development of thrombosis in newborns was determined, as well as quantitative estimation of their contribution was presented.

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

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

Treatment of the newborn with a floating thrombus in the right atrium: case report

Venous thrombosis in newborns in pediatric surgery is rare. Aim of the article: description of the case of treatment of a newborn with a floating thrombus of the right atrium. This article reports the case of a 26-day-old child with a floating right atrium thrombus with a background of late neonatal sepsis, septicemia, osteomyelitis of the proximal humerus, severe anemia and bacterial endocarditis. Primary cause of the right atrial thrombus was a complicated course of pregnancy with anemia, inflammatory disease and colpitis of the mother in the obstetric history. Features of presented case: surgical removal of thrombus with cardiopulmonary bypass. Conclusion ― Thrombosis of the heart cavities in newborns is a rare and dangerous condition, requiring urgent treatment. The presence of a floating thrombus in the heart cavity, is an indication for the surgical removal of a thrombus.

Arterial Thrombosis Secondary to Cardiac Catheterization in Neonates

Objective: Cardiac catheterization is one of the basic procedures applied in the diagnosis and treatment of cardiovascular diseases. Development of thrombosis is a serious complication of catheterization. In this study, the frequency and the factors affecting the development of arterial thrombosis were prospectively evaluated in neonates who were subjected to diagnostic or interventional cardiac catheterization. Methods: Twenty newborns that received femoral artery catheterization within 6-month period were enrolled in this study. Blood samples were taken for complete blood count, prothrombin, activated partial thromboplastin time, INR ratio and mutations of factorV Leiden, prothrombin 20210A, methylenetetrahydrofolate reductase C667T and A1298 before the procedure. 100 U/kg bolus of heparin was infused during catheterization. 28 U/kg/hour infusion of heparin was given to the patients with clinically suspected thrombosis during first few hours after catheterization. Doppler ultrasonography was performed in all patients within 6 hours after catheterization. Results: The gestational age of patients ranged from 31 to 40 weeks (median 39). Mean birth weight was 2996 ± 589 (1880-4000 gr). Arterial thrombosis was detected in 10 patients by Doppler USG. On development of arterial thrombosis, patient age, gender, diagnosis, treatments, platelet count, hemoglobin, prothrombin and activated partial thromboplastin time values, FactorV Leiden, prothrombin 20210A, methylenetetrahydrofolate reductase C667T and A1298 mutations were found as not impacting (p>0.05). Those who were found to have thrombosis in Doppler ultrasonography had lower INR levels compared to others (p= 0.023). Conclusions: The rate of femoral arterial thrombosis in newborns after catheterization detected by Doppler ultrasonography was 50% in this study. Our data suggest that early clinical assessment for the diagnosis of thrombosis may be misleading but Doppler ultrasonography may be helpful early detection. Further studies are needed to prediction appropriate drugs and/or doses for prevention of thrombosis after arterial catheterization in newborns.

Sequential sonographic features in neonatal renal vein thrombosis.

Renal vein thrombosis in newborns is a rare but serious and acute disease. Clinical representations of RVT can vary from discrete symptoms to life-threatening conditions. Therefore imaging, and in particular sonography, plays an important role in the diagnosis of RVT in neonates. Gray-scale, color and spectral/power Doppler ultrasound are all used in the diagnosis of RVT. We present retrospective sequential ultrasonic imaging of three patients (two term and one preterm infant) with findings characteristic of RVT. Initial ultrasound diagnostic features include: renal enlargement, echogenic medullary streaks, lack of the flow pattern characteristic of arcuate vessels and subsequently loss of corticomedullary differentiation, reduced echogenicity around pyramids and echogenic band at the extreme apex of the pyramid. Higher resistance index or less pulsatile venous flow on the affected kidney are helpful Doppler signs. Knowledge and identification of specific features of each phase of the evolution of RTV seems essential to prompt diagnosis. We would like to highlight the evolution of specific sonographic features in each subsequent phase of RVT.

Radiological and clinical features of cerebral sinovenous thrombosis in newborns and older children

Cerebral sinovenous thrombosis (CSVT) represents an increasingly recognized cause of pediatric stroke. Our purpose was to assess gender and age differences in the etiology, clinical presentation, and imaging features of CSVT in neonates and older children. Subjects aged newborn to 18years diagnosed with CSVT at the Lille university hospital between 2011 and 2014 were included. Eleven neonates and 16non-neonates constituted the study population. The incidence of CSVT was significantly higher in male newborns. Clinical presentation did not vary significantly between the groups. Risk factors were age-dependent, with acute systemic illnesses significantly predominating in neonates (54%), whereas local infections, prothrombotic conditions, and trauma were more common in older children (36, 27, and 27% respectively). No predisposing factor could be identified in 36% of the neonates as compared to less than 5% of the non-neonates. Thrombosis of the deep venous structures was documented in 73% of the neonates whereas involvement of the superficial sinuses was significantly more frequent in the non-neonates group. Venous infarctions and extraparenchymal hemorrhages were significantly more frequent in the neonates group. Male patients are at higher risk for CSVT than females. In neonates, involvement of the deep venous structures is significantly more common. Brain parenchymal and extraparenchymal changes occur more frequently in this age group than in older children.

Fetal Thrombotic Vasculopathy and Perinatal Thrombosis: Should all Placentas be Examined?

Numerous fetal placenta vascular lesions seem to be a predisposing condition for some types of perinatal disease. Placental disease and newborn thromboses might be both manifestations of the same underlying disorder. Objective of this study is to describe pathological lesions of the placenta in newborns with perinatal thrombosis. We present retrospective data review and analysis regarding neonates admitted at our neonatal intensive care unit and diagnosed with an episode of thromboembolic events (TE) in the period from 2009 to 2013; among them we report three cases of perinatal thrombosis in newborns whose placentas demonstrated fetal thrombotic vasculopathy (FTV). In all the three cases a prothrombotic maternal condition was found, and in one patient a maternal infection with chorioamnionitis; the histological examination of placenta, required soon after birth for maternal pathological conditions, was important in confirming and explaining the clinical diagnosis of neonatal thrombosis and for the management of future pregnancies. It is proposed that placenta of newborns with TE in first days of life should always be examined, for its association with FTV and thus the storage of placentas for a week after birth should be routinely implemented.

Statement of Retraction: Sellitto M, Messina F. “Central venous catheterization and thrombosis in newborns: update on diagnosis and management”

Statement of Retraction: Sellitto M, Messina F. “Central venous catheterization and thrombosis in newborns: update on diagnosis and management”

Giant right atrial thrombus in premature newborn

Pediatric guidelines for treatment options of right atrial thrombosis in newborn are quite limited. Herein we present a case with giant atrial thrombosis resulting from umbilical venous catheter and intend to discuss the therapy in the area of current literature on right atrial thrombus in newborn and children.

C0299 Thrombosis in newborns and neonates. Unsolved problems

C0299 Thrombosis in newborns and neonates. Unsolved problems

RETRACTED: Central venous catheterization and thrombosis in newborns: update on diagnosis and management

RETRACTION

Thrombosis in newborns: experience from 31 cases

Thrombosis is the result of congenital or acquired prothrombotic risk factors. The incidence of thrombosis in the paediatric population is highest in newborns, as about 10% of thrombotic events occur in the first four weeks of life. Haemostasis in a newborn, though still developing, is a well balanced mechanism. About 90% of all thrombotic events are due to acquired and the rest to congenital risk factors. The aim of our study was to estimate the incidence of thrombosis in a population of Slovenian newborns and to study risk factors, location and treatment of thrombotic events. Inpatient charts of newborns with thrombosis, admitted to a tertiary neonatology centre and paediatric intensive care unit between 2004 and 2011, were studied retrospectively. Family history, location, aetiology and treatment of thrombosis were analysed. Thirty one newborns, 17 boys (54.8%) and 14 girls (45.2%), with 31 thrombotic events were found. There were 17 cases (54.8%) of arterial and 14 cases (45.2%) of venous thrombosis. A family history of thrombophilia was found in two cases (6.5%). Twenty six cases (83.9%) were contributed to acquired risk factors and five (16.1%) to congenital aetiology. Four cases (12.8%) were treated, two with anticoagulation, one with thrombolysis and one with both. The estimated incidence of thrombosis was 0.17 per 1000 live births. Our data showed a higher incidence of thrombosis in Slovenian newborns and a higher incidence of congenital prothrombotic risk factors than in the data published so far.

Tissue Factor Promoter Haplotype Amplifies Inflammatory Response Via p38-MAPK in Neonatal Compared to Adult Human Microvascular Endothelial Cells

Abstract 1150Age- and tissue-dependent diversity of the vascular endothelium may contribute to the devastating sequelae of inflammation and thrombosis in newborn infants, who often develop multi-organ failure from excessive coagulation-related tissue necrosis. Our previous studies have demonstrated that cytokine and cytoadhesion molecule expression by IL-1- or TNF-α-activated macrovascular endothelial cells (EC) is altered depending upon their vascular origin. Since the microvasculature is especially prone to thrombotic complications of inflammation, we compared expression of several coagulation factors between neonatal and adult human microvascular EC (HMVEC; Lonza) in response to IL-1, and found only tissue factor (TF) was expressed differentially.In addition to the differences in TF expression between neonatal vs. adult HMVEC, we also found high variability among individual neonatal HMVEC. This finding led us to investigate the possible contribution of two polymorphic TF promoter haplotypes reported to play a role in TF gene regulation. Genotyping revealed that neonatal HMVEC homozygous for an 18 base pair (bp) deletion at −1208 (D/D) expressed much higher levels of TF mRNA in response to IL-1 than those homozygous (I/I) or heterozygous (I/D) for the 18 bp insertion, as had also been previously reported for human umbilical vein EC. Moreover, IL-1-stimulated TF mRNA, protein, and activity levels were significantly (p<0.05) higher (4-fold, 2-fold, and 4-fold) in D/D neonatal than D/D adult HMVEC. Importantly, these results suggested that the D/D haplotype induces a uniquely robust response to IL-1 by the TF promoter in neonatal HMVEC.Signal transduction pathway macroarray studies (SABiosciences), to compare IL-1 response, showed a striking Jak-STAT pathway activation in neonatal compared to adult HMVEC. Further analysis found that IL-1 induced a 5.8-fold increase in phosphorylation of p38-MAPK by neonatal HMVEC, significantly greater than the 1.9-fold increase by adult HMVEC (p<0.05). Inhibition of the p38-MAPK pathway with SB203580 eliminated the differential Jak-STAT activation and significantly reduced TF mRNA by 58% vs. 20% (p<0.01) in IL-1-stimulated D/D neonatal vs. adult HMVEC. These results suggest that IL-1 hyperactivation of p38-MAPK, possibly regulated by the Jak-STAT pathway, plays a role in up-regulating D/D neonatal HMVEC TF expression.The following schematic model summarizes the hypothetical response of the neonatal HMVEC TF gene to IL-1: [Display omitted] This model highlights key components of both the p38-MAPK and NF-κB regulatory pathways. It also illustrates hyperactivation of the p38 pathway (shown as thicker arrows) and its potential up-regulation of one, or more, known, or yet-to-be characterized, D/D promoter haplotype-specific transcription factors (shown as hatched arrows) in neonatal HMVEC.This amplified inflammatory response of neonatal HMVEC appears to represent a critical developmental transition between the fetal and adult states of vascular gene regulation and expression, providing a potential basis for the increased frequency and morbidity associated with microvascular thrombosis in susceptible newborns. Disclosures:No relevant conflicts of interest to declare.

Low-molecular-weight heparin in pediatric patients.

The incidence of thromboembolic events (TEs) in childhood is greatly underestimated. Two age groups account for approximately 70% of TEs in childhood: infants and teenagers. There are several predisposing risk factors for newborns such as small vessels, high hematocrit, and a unique neonatal hemostatic system. Central venous lines contribute to 80% of deep vein thrombosis in newborns. Other risk factors for all children are shock syndromes, trauma, surgery, heart and kidney disease, and acquired or hereditary thrombophilias. The best prophylaxis is to recognize, avoid, and remove risk factors if possible. This is particularly relevant in childhood, where risk factors can be found in the majority of TEs. The serious sequelae of TEs (mortality, and short- and long-term morbidity) require therapeutic intervention. Unfractionated heparin (UFH) has the following disadvantages: age-dependent unpredictable pharmacokinetics, the need for intravenous access for therapy and monitoring, delays in achieving therapeutic ranges, bleeding risk, the risk of heparin-induced thrombocytopenia, and osteoporosis with long-term use. Oral anticoagulants, in addition to some of these disadvantages, show considerable variation by diet (especially if there is a change from breast to bottle feeding), medication, and intercurrent illness. Review of case reports and cohort studies on 728 children treated with low-molecular-weight heparin (LMWH) indicate the following advantages over UFH: minimal monitoring, ease of administration (subcutaneous), and possibly equivalent efficacy and safety. Dose recommendations for pediatric patients cannot be directly extrapolated from those for adult patients. If dosages are calculated according to body weight, infants < 3 months (or < 5 kg) need approximately 50% more LMWH than older children or adults to reach prophylactic or therapeutic anti-factor Xa levels. Further studies are necessary to address the following: the importance of risk factors, the necessity of screening for hereditary thrombophilia, the efficacy and safety of treatment, and side effects and duration of treatment. Thromboembolic events (TEs) are considered to be rare in children. However, recent surveys reveal that TEs in children occur more often than suspected. The incidence is greatly underestimated because TEs are usually overlooked. Retrospective surveys in children treated for acute lymphoblastic leukemia with corticosteroids and asparaginase revealed clinically symptomatic TE in only 2 to 12% of patients. However, in prospective studies with routine imaging, the incidence was more than 20%. The objectives of this article are to update the present knowledge on TEs in children, including incidence, predominant age groups, risk factors, diagnosis, and indications for prophylaxis and therapy; and to discuss the use of low-molecular-weight heparin (LMWH) in children.