The use of umbilical venous catheters (UVCs) in the perinatal period may be associated with severe complications, including the occurrence of portal vein thrombosis (PVT).

To assess the incidence of UVC-related PVT in infants with postnatal age up to three months.

A systematic and comprehensive database searching (PubMed, Cochrane Library, Scopus, Web of Science) was performed for studies from 1980 to 2020 (the search was last updated on November 28, 2020). We included in the final analyses all peer-reviewed prospective cohort studies, retrospective cohort studies and case-control studies. The reference lists of included articles were hand-searched to identify additional studies of interest. Studies were considered eligible when they included infants with postnatal age up to three months with UVC-associated PVT. Incidence estimates were pooled by using random effects meta-analyses. The quality of included studies was assessed using the Newcastle-Ottawa scale. The systematic review was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines.

Overall, 16 studies were considered eligible and included in the final analyses. The data confirmed the relevant risk of UVC-related thrombosis. The mean pooled incidence of such condition was 12%, although it varied across studies (0%-49%). In 15/16 studies (94%), diagnosis of thrombosis was made accidentally during routine screening controls, whilst in 1/16 study (6%) targeted imaging assessments were carried out in neonates with clinical concerns for a thrombus. Tip position was investigated by abdominal ultrasound (US) alone in 1/16 (6%) studies, by a combination of radiography and abdominal US in 14/16 (88%) studies and by a combination of radiography, abdominal US and echocardiography in 1/16 (6%) studies.

To the best of our knowledge, this is the first systematic review specifically investigating the incidence of UVC-related PVT. The use of UVCs requires a high index of suspicion, because its use is significantly associated with PVT. Well-designed prospective studies are required to assess the optimal approach to prevent UVC-related thrombosis of the portal system.

Neonatal inferior vena cava syndrome (IVCS), though uncommon, is associated with significant morbidity and mortality. Information on risk factors, diagnosis, treatment, and outcomes is limited. This review comprised 61 neonates across 33 reports. Thrombosis occurred in 98% and 42% involved a central venous catheter. Diagnosis was mainly established by ultrasound in 82%. Therapeutically, heparin was employed in 36% and thrombolysis in 18% of the cases. The overall mortality was 23%. An algorithm of clinical signs, investigation, and management is presented. Well-designed prospective studies are needed to establish a concrete investigational approach to neonatal IVCS and institute safe, evidence-based treatment.

Catheter-related arterial thrombosis (CAT) are increasingly recognized in infants and children. Insufficient data are available on the incidence, risk factors, treatment and outcome of these thrombotic events. This work provides consensus recommendations for future research on catheter-related arterial thrombosis in the paediatric population. In particular, future studies should distinguish between CAT due to indwelling arterial catheters or cardiac catheterization in two different subpopulations (neonates and older children). Further studies should investigate sensitivity and specificity of clinical signs and symptoms for early screening of CAT and the most appropriate imaging modality, focusing on ultrasound due to better feasibility in the very young pediatric population. Adequately powered, well-designed clinical trials should investigate efficacy and safety of different treatment and prevention strategies as well as the risk for and the optimal management of short- and long-term complications.

A 3-month-old boy presented to hospital in cardiac arrest, dehydrated, with a blood sodium of 158.4 mmol/L. He had been febrile, not feeding normally and refusing fluids. Despite attempts at resuscitation with rehydration, he was declared dead. At autopsy, the kidneys were uniformly enlarged with thrombi within intraparenchymal tributaries of the renal veins bilaterally. Death was due to bilateral renal venous system thrombosis with hypernatremic dehydration. It is likely that the dehydration resulted both from increased requirements for fluid due to fever and from inadequate oral intake. Lethal renal venous thrombosis is a rare multifactorial condition that should be suspected in all infants with histories of hypernatremic dehydration with hypotension. Although there may be no obvious renal vein thrombosis at the time of dissection, microscopy may reveal intraparenchymal venous thromboses. As inherited prothrombotic states are associated with renal venous thrombosis, hematologic evaluation of immediate family members would be in order.

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by vascular thrombosis and/or pregnancy morbidity associated with the persistent presence of antiphospholipid antibodies (aPL) including lupus anticoagulant (LA), anticardiolipin antibodies (aCL), and anti-β2 glycoprotein I antibodies (aβ2GPI).

APS is considered as the most common acquired hypercoagulation state of autoimmune origin in children. Unfortunately, data about incidence, prevalence, thrombosis risk and effective treatment in paediatric APS are limited and unmethodical. Expert commentary: This review summarizes recent clinical, laboratory and therapy characterization of paediatric APS and emphasizes the differences between paediatric and adult populations.

Cerebral venous thrombosis (CVT) is a severe multifactorial condition with various clinical manifestations that may include headache, papilledema, seizures, focal deficits, coma and death. The mortality rate of untreated CVT is up to 50%, but it drops to 10% when CVT is properly treated. Prevention of CVT is feasible through healthy lifestyle, genetic counseling, molecular genetic analysis for common thrombophilia-related mutations, and prophylactic anticoagulative medication.

Antiphospholipid syndrome (APS) is a multisystem autoimmune condition characterized by vascular thromboses associated with persistently positive antiphospholipid antibodies. There is currently a paucity of data (incidence, prevalence, thrombosis risk, and effective treatment) in pediatric APS. The purpose of this report is to review the current literature on APS in children and neonates, identify the gaps in current knowledge, and suggest avenues for studies to fill those gaps.

Pediatric thrombosis and thrombophilia are increasingly recognized and studied. In this article, both the inherited and acquired factors for the development of thrombosis in neonates and children are categorized using the elements of Virchow's triad: stasis, hypercoagulable state, and vascular injury. The indications and rationale for performing thrombophilia testing are described. Also included are discussions on who, how, when, and why to test. Finally, recommendations for the use of contraceptives for adolescent females with a family history of thrombosis are outlined.

In neonates and infants with idiopathic venous thrombosis (VTE) and in pediatric populations in which thromboses were associated with medical diseases, inherited thrombophilia (IT) have been described as risk factors. Follow-up data for VTE recurrence in neonates suggest a recurrence rate between 3% in provoked and 21% in idiopathic VTE. Apart from underlying medical conditions, recently reported systematic reviews on pediatric VTE have shown significant associations between factor V G1691A, factor II G20210A, and deficiencies of protein C, protein S and antithrombin, even more pronounced when combined IT were involved. Independent from the age at first VTE onset, the pooled odds ratios (OR: single IT) for VTE ranged from 2.4 for the factor II G20210A mutation to 9.4 in neonates and infants with antithrombin deficiency. The pooled OR for persistent antiphospholipid antibodies/lupus anticoagulants was 4.9 for pediatric patients with venous VTE. The factor II G20210A mutation (OR: 2.1), and deficiencies of protein C (OR: 2.4), S (OR: 3.1) and antithrombin (OR: 3.0) also played a significant role at recurrence. Based on these data, screening and treatment algorithms must be discussed.

Whereas thrombotic events in critically ill children do not occur as commonly as in adults, they are being recognized with increasing frequency in the pediatric intensive care unit. The reasons for this are not clear but likely include an increased awareness of the problem and the ability to make a diagnosis using relatively noninvasive tests. In this section, I attempt to define the extent of the problem, summarize and discuss the relevant literature (pointing out where published experience in the pediatric population differs from that in adult patients), and suggest some guidelines regarding thrombophilia treatment and the management of thrombotic events.

The use of molecular diagnostic techniques in clinical and research hemostasis laboratories is increasing as genetic factors that affect the procoagulant and anticoagulant systems are identified. Many of these molecular alterations are associated with thrombotic tendencies, whereas others tip the hemostatic balance in favor of bleeding. In either scenario, molecular testing may serve as a primary diagnostic modality or may provide information that complements clot-based "functional" assays. The clinical application of DNA-based testing continues to expand since the discoveries of the factor V Leiden and prothrombin G20210A gene mutations. Indications for genetic testing continue to evolve as the underlying causes of hemostatic disorders are better understood. Further development of molecular assays depends on their proved utility in the clinical management and treatment of these complex multifactorial disorders.

Thrombotic events in children have become an increasingly common problem, particularly in paediatric tertiary care hospitals. The prevalence of inherited thrombophilia in children who develop thrombosis varies substantially depending on the population. Children who develop thrombosis, as well as those who have not but have a positive family history, are frequently tested for inherited thrombophilia. The clinical utility of performing such tests has been questioned, in both adults and children. This review will examine the practise of testing for inherited thrombophilia in children, focusing on the rationale for testing and highlighting areas in which more evidence is needed prior to making strong recommendations. Future studies, many of which are currently being performed or proposed, are necessary to address many of the unanswered questions.

Renal vein thrombosis, although rare in adults, is well recognized in neonates and is one of the most common manifestations of neonatal thromboembolic events. The etiology of renal vein thrombosis remains unidentified in the majority of cases. We report a case of renal vein thrombosis in a neonate associated with elevated maternal lipoprotein (a).

A full-term female infant, appropriate for gestational age, was born via spontaneous vaginal delivery to an 18-year-old primigravida. The infant's birth weight was 3680 g and the Apgar scores were eight and nine at 1 and 5 minutes respectively. Evaluation of the infant in the newborn nursery revealed a palpable mass in the right lumbar area. Tests revealed hematuria and a high serum creatinine level of 1.5 mg/dl. An abdominal ultrasound Doppler flow study demonstrated an enlarged right kidney, right renal vein thrombosis, and progression of the thrombosis to the inferior vena cava. There was no evidence of saggital sinus thrombosis. An extensive work-up of parents for hypercoagulable conditions was remarkable for a higher plasma lipoprotein (a) level of 73 mg/dl and an elevated fibrinogen level of 512 mg/dl in the mother. All paternal levels were normal. The plasma lipoprotein (a) level in the neonate was also normal. The neonate was treated with low molecular weight heparin (enoxaparin) at 1.5 mg/kg/day every 12 hours for 2 months, at which time a follow-up ultrasound Doppler flow study showed resolution of the thrombosis in both the renal vein and the inferior vena cava.

There have been no studies to date that have explored the effect of abnormal maternal risk factors on fetal hemostasis. A case-control study is required to investigate whether elevated levels of maternal lipoprotein (a) may be a risk factor for neonatal thrombotic processes. Although infants with this presentation are typically treated with anticoagulation, there is a lack of evidence-based guidelines. Treatment modalities vary between study and treatment centers which warrants the establishment of a national registry.

Insertion of an intravascular catheter is the most common invasive procedure in the neonatal ICU. With every passing decade, technological innovations in catheter materials and sizes have allowed vascular access in infants who are smaller and sicker for purposes of blood pressure monitoring, blood sampling, and infusion of intravenous fluids and medications. There is, however, growing recognition of potential risks to life and limb associated with the use of intravascular catheters. This article reviews complications of venous and arterial catheters in the neonatal ICU and discusses treatment approaches and methods to prevent such complications, based on current evidence.