Neonatal Thrombosis Research Articles

Elevated Risk of Thrombosis in Neonates Undergoing Initial Palliative Cardiac Surgery

Thrombotic events cause significant morbidity and mortality in children who undergo surgery for complex congenital cardiac disease. We prospectively evaluated the incidence of thrombosis and examined preoperative and postoperative laboratory tests of coagulation and inflammation in neonates experiencing initial surgical palliation for variations of single ventricle physiology. Neonates (<30 days) requiring initial surgical palliation were studied. All subjects received aspirin from postoperative day 1 onward. Thromboses were diagnosed by serial transthoracic echocardiograms, vascular imaging, and interstage cardiac catheterizations according to predefined criteria. Twenty-two neonates, age 1 to 11 days (mean 4 +/- 2.5) were studied. Follow-up ranged from three hours to 18 months (median, 212 days). Eight infants died. Four of the 14 subjects who survived (28%), and one of the eight who died (12.5%), had evidence of thrombosis identified over a range of four hours to nine months postoperatively (median 14 days). When compared with reference values established in healthy children, preoperative subject hematocrit (Hct), platelet count, factors II, V, VII, VIII, and X, antithrombin, protein C, and soluble CD40 ligand measures were significantly lower, and the prothrombin time and partial thromboplastin time were significantly higher. Postoperative C reactive protein (CRP) was significantly higher, and Hct and platelet count significantly lower, than preoperative values. Thrombotic events were significantly related to high preoperative CRP (p = 0.02). Thrombotic complications occur frequently in neonates undergoing initial palliative surgery, suggesting that aspirin therapy alone may constitute inadequate protection. Elevated preoperative CRP appears to be associated with increased thrombotic risk.

NNP017 Neonatal herpes-virus encephalitis and venous thrombosis

NNP017 Neonatal herpes-virus encephalitis and venous thrombosis

Enoxaparin Use in the Neonatal Intensive Care Unit: Experience Over 8 Years

To evaluate the effectiveness and safety of enoxaparin therapy in a neonatal intensive care unit (NICU). Retrospective chart review. Level III NICU in a Canadian academic center. All neonates treated with enoxaparin while in the NICU between January 1, 1998, and June 1, 2006. Data abstracted included patient demographics, diagnosis of thrombosis and its progression, enoxaparin dosages with corresponding antifactor Xa levels, and adverse events. Sixteen neonates (four term, 12 preterm) were treated with enoxaparin at a mean +/- SD initial subcutaneous dose of 1.41 +/- 0.15 mg/kg every 12 hours. The target therapeutic range (antifactor Xa level 0.5-1.0 U/ml) was achieved by 12 infants at a mean +/- SD dose of 1.92 +/- 0.43 mg/kg every 12 hours, after a mean of 5.6 days (range 1-15 days). Preterm infants required a higher dose (per kilogram) compared with term infants to maintain therapeutic antifactor Xa levels (mean +/- SD 1.94 +/- 0.39 vs 1.65 +/- 0.14 mg/kg every 12 hrs, p<0.001). Enoxaparin doses were more strongly correlated to antifactor Xa levels in term infants (r(2)=0.51, p<0.001) compared with preterm infants (r(2)=0.20, p<0.001). Ten (71%) of 14 thromboembolic events resolved, either partially or completely, at a mean of 39 days (range 8-61 days) of enoxaparin therapy. Nine infants (56%) experienced minor local adverse effects at the site of the indwelling subcutaneous catheter (induration, bruises, hematomas, or leakage). Systemic adverse events that were possibly related to enoxaparin therapy included osteopenia (one infant), scleral hemorrhage (one), and minor gastrointestinal tract bleeding (three) found in gastric feeding tubes. No adverse effects were associated with antifactor Xa levels greater than 1.0 U/ml. Enoxaparin may be effective in the treatment of neonatal thrombosis. An initial dosage of 1.5 mg/kg every 12 hours is likely inadequate to obtain therapeutic antifactor Xa levels rapidly and differs for term and preterm neonates. Therapeutic levels in preterm infants may be more variable, and the pharmacokinetics of this drug in preterm infants requires further evaluation. Future studies in neonates should prospectively evaluate a higher starting dose of enoxaparin to document effectiveness, acceptance, compliance with treatment guidelines, and adverse effects.

Atypical Presentation of Prader-Willi Syndrome with Cerebral Venous Thrombosis: Association or Fortuity?

A newborn female born at term was admitted at 28 hours for seizures and generalized hypotonia. Cerebral ultrasound showed a right temporal echogenic lesion confirmed on MRI and thought to be secondary to thrombosis of the vein of Labbé. The EEG showed epileptic discharges over the right temporal region. Extensive thrombotic studies revealed a transiently decreased PTT consistent with a prothrombotic state. The hypotonia did not resolve after the acute phase as expected, raising the possibility of another underlying cause. Because of a peculiar phenotype with almond-shaped eyes and bitemporal depression, Prader-Willi syndrome (PWS) was suspected. Methylation analysis confirmed PWS, FISH analysis excluded a deletion in 15q11-q13, maternal uniparental disomy (UPD) was confirmed. To our knowledge, this is the first report of the association of a neonatal venous thrombosis and a PW Syndrome.

Thrombose aortique néonatale majeure : à propos d'une observation

Aortic thrombosis is a rare and severe condition in neonates which often is revealed by ischemia of lower limbs. We report a case of major aortic thrombosis revealed by renal failure, hematuria and dehydration in a 10-day-old girl. Clinical features consisted in hypertension at upper limbs without ischemic signs of the lower limbs. Diagnosis was made using renal Doppler ultrasound. Thrombosis resolved after thrombolytic treatment and anticoagulation using heparin. The case report is followed by a review of the literature dealing with clinical, etiological and therapeutic aspects of neonatal arterial thrombosis.

Idiopathic neonatal aortic thrombosis

We report a term neonate with severe aortic thrombosis involving the aorto-iliac segment and leading to renal failure. This patient did not have any predisposing risk factors. The authors have also reviewed the literature on neonatal aortic thrombosis and discuss the need for evolving evidence based consensus guidelines for management of this catastrophe.

Risk Factors for Umbilical Venous Catheter-Associated Thrombosis in Very Low Birth Weight Infants.

Background: Thrombosis in neonates is a rare but serious occurrence that is usually associated with central catheterization. Among acquired risk factors, thrombocytosis has often been thought to play a role in neonatal thrombosis, but little evidence exists to support this impression.Objectives:To investigate the effects of platelet count on catheter-related thrombosis in neonates.To investigate the effects of being small for gestational age (SGA) on catheter-related thrombosis in neonates.We hypothesized that neonates with catheter-related thrombosis would have relative thrombocytosis and would be SGA.Methods: The present retrospective study was performed using data from a randomized trial of duration of umbilical venous catheters (UVC) placement among infants <1250 g birth weight (Butler-O'Hara, Pediatrics 2006; 118:e25–e35). In this study, all subjects had UVC that were left in place for up to 28 days. All subjects were screened biweekly for thrombi with echocardiograms. Twenty-two cases of UVC-associated thrombosis were identified in this sample. The remaining study sample (n=188) served as controls. Data on thrombosis, platelets, gestational age, birth weight, hematocrit, serum sodium (as a measure of dehydration), duration of catheter placement, study group assignment and demographic factors were collected using database and record review.Results: Among the total subjects (n=210), 112 (53%) were males and 126 (60%) were Caucasians, with mean gestational age of 27.7 ± 2.1 wks (SD) and mean birth weight of 923 ± 195g. Bivariate analysis revealed significant association of thrombosis with hematocrit >55% in the first wk (OR, 5.4; 95% CI, 2.0–14.6; p=0.0003), being small for gestational age (OR, 2.9; 95% CI, 1.2–7.4; p=0.02), lower platelet counts in the first wk (193 ± 57 x 103/uL in infants with thrombus vs. 238 ± 70 x 103/uL in infants without thrombus, p=0.005) and gestational age (27.8 ± 2.5 wks in infants with thrombus vs. 27.6 ± 2.0 wks in infants without thrombus, p=0.02). In multivariate logistic regression analysis, only higher hematocrit was independently associated with thrombus (OR, 3.9; 95% CI 1.3–12.6; p=0.02). There was a trend towards an independent negative association between platelets and thrombosis (OR, 0.93 per 10 x 103/uL platelet rise; 95% CI, 0.85–1.02; p=0.12).Conclusion: This study demonstrates a significant, independent association of elevated hematocrit and development of UVC-associated thrombosis. We did not observe an increased risk of thrombosis with increased platelet count. Careful monitoring for catheter-associated thrombosis is suggested for neonates with hematocrit >55% in the first wk of life.

Renal Outcome of Neonatal Renal Venous Thrombosis: Review of 28 Patients and Effectiveness of Fibrinolytics and Heparin in 10 Patients

Neonatal renal venous thrombosis is a rare disorder that can result in severe renal damage. To evaluate the experience over 10 years and review the effectiveness of fibrinolytic and/or heparin therapy, chart reviews were performed for newborns with renal venous thrombosis. PATIENTS, INTERVENTIONS, AND OUTCOME MEASURES: Twenty-eight newborns with renal venous thrombosis were treated at Children's Hospitals and Clinics of Minnesota and Fairview University Medical Center from 1991 to 2001. Unilateral involvement was noted in 25 neonates (89%) and bilateral involvement in 3 (11%). Unilateral renal venous thrombosis affected mostly term infants, whereas 2 of 3 infants with bilateral renal venous thrombosis were <32 weeks' gestational age (birth weight: 745-1505 g). One mother had antiphospholipid syndrome. Of 11 neonates evaluated for congenital thrombophilia, 1 had the factor V Leiden mutation. Ten neonates received either unfractionated or low molecular weight heparin for 3 days to 7 months. Three infants with unilateral renal venous thrombosis treated with heparin alone did not seem to benefit from such therapy. Seven neonates were treated with fibrinolytics and unfractionated heparin (4 neonates with unilateral renal venous thrombosis and 3 with bilateral renal venous thrombosis). Treatment with fibrinolytics did not result in restoration of renal function in the 4 neonates with unilateral renal venous thrombosis but was associated with return of almost normal function in the 2 neonates with bilateral renal venous thrombosis who received fibrinolytics immediately after renal venous thrombosis diagnosis. Two neonates treated with fibrinolytics suffered bleeding complications at the area of adrenal hemorrhage. Two neonates (not treated for renal venous thrombosis) died as a result of underlying disease. Most neonatal renal venous thrombosis is unilateral and does not respond to fibrinolytic therapy and heparin. The use of fibrinolytics may prevent chronic renal failure in neonates with bilateral renal venous thrombosis if begun within 24 hours of diagnosis. Fibrinolytic therapy, however, is associated with a risk of bleeding, specifically if there is an associated adrenal hemorrhage.

Thrombosis and Thrombophilia in Children: A Systematic Review

Thrombotic events are uncommon disorders in childhood but increasingly recognized due to the progress made in the understanding of the hemostasis system and the importance of thromboembolic disorders in children. Multiple clinical underlying conditions and prothrombotic disorders contribute to the development of thrombosis in neonates and children. In recent years programs have emerged that specialize in the diagnosis, prevention, and treatment of thrombosis in children. This review summarizes the current knowledge of the risk factors for thromboembolic events in the venous and arterial systems in children, the use of antithrombotic prophylaxis, and the role of thrombophilia. First, the clinical manifestations and the problems of diagnosing venous thromboembolic diseases and cerebrovascular diseases in children are reviewed. The prophylactic use of anticoagulants in children is also discussed. Unfortunately there are no large prospective randomized trials in children, thus guidelines are based on small studies or on extrapolation of data from adults. Second, the impact of prothrombotic defects in pediatric patients and the issue of routine testing for these disturbances are reviewed.

Heterozygous methylenetetrahydrofolate reductase 677C-T gene mutation with mild hyperhomocysteinemia associated with intrauterine iliofemoral artery thrombosis

Neonatal thrombosis is a serious event that can cause mortality or severe morbidity. Newborn-related factors, including genetic prothrombotic risk factors, may affect the occurrence of neonatal thrombosis. In this report, a case of intrauterine iliofemoral arterial thrombosis associated with mild hyperhomocysteinemia caused by methylenetetrahydrofolate reductase 677C-T gene mutation is presented. We suggest that methylenetetrahydrofolate reductase gene mutation might be investigated in neonates and their families presenting with thromboembolic disease.

Bilateral renal vein thrombosis in a twin newborn without known risk factors

Neonatal renal vein thrombosis (RVT) is associated with neonatal stress, catheters and genetic prothrombotic risk factors. In an unusual case of bilateral RVT a twin newborn showed initial good adaptation at birth (weight 2,720 g). The placenta was monochorionic, diamnionic. The infant (gestational week 37) exhibited a severe macrohematuria within 24 hours after birth. Sonography of the kidneys showed a dense cortical parenchyma, loss of cortico-medullary differentiation and negative diastolic flow in both renal arteries and veins, while no thrombus in the main renal veins could be detected. No prothrombotic blood parameters and positive infection serology were detected. Because of acute renal failure peritoneal dialysis was necessary for 6 weeks. The patient was treated by heparinization for 5 days. Interestingly, it was kidney biopsy which confirmed the diagnosis of RVT in addition to the clinical presentation, whereas sonography was unspecific. Histology exhibited the picture of an ischemic contracted kidney with numerous siderophages. At present (age 19 months), the patient suffers from chronic renal failure (calculated glomerular filtration rate according to Schwartz 12 ml/min/1.73 m2). In conclusion, our case teaches that, despite the lack of a clinically obvious shock event, absence of known risk factors and indirect ultrasound findings, renal vein thrombosis should be considered in a macrohematuric newborn with renal failure. For clinical suspicion of RVT correct therapy was initiated, however, the diagnosis remained unclear until a renal biopsy was performed.

Autoimmunity and Pregnancy

In women who suffer from rheumatic diseases (RDs) the risk of repeated fetal loss, intrauterine growth restriction, and preterm birth remains higher than in the general population. Antiphospholipid antibodies are frequently observed in patients with systemic lupus erythematosus (SLE). They are associated with recurrent pregnancy losses that may occur at any age of gestation. The cause of fetal death is believed to be intraplacental thrombosis, although other pathologic mechanisms have been described. A recent study has described the increased frequency of learning disabilities in the offspring of SLE patients; case reports of neonatal thrombosis are very rare. Transplacental passage of IgG anti-Ro/SS-A antibodies is linked to neonatal lupus (2%). The main manifestation is congenital heart block (CHB) due to the binding of anti-Ro/SS-A antibodies to cardiac conduction tissue and to the consequent inflammatory/fibroid reaction. Neonatal lupus also includes cutaneous, hematologic, and hepatobiliary manifestations, which are typically transient. Incomplete CHB can be treated with fluorinated corticosteroids to prevent the progression and decrease inflammation. Intravenous immunoglobulin, decreasing the tranplacental passage of anti-Ro/SS-A, has been proposed as prophylactic therapy in patients who had one or more child with CHB. Transplacental passage of antiplatelet antibodies, in about 10% of mothers with SLE, can induce thrombocytopenia in the fetus or the neonate. Patients with RD have a higher incidence of anxiety and depression compared to the general population, interfering with parenthood and the upbringing of children.

Trombosis venosa cerebral neonatal. Diagnóstico por angiorresonancia magnética

Neonatal cerebral venous thrombosis (NCVT) is a rare, severe neuropathology of multiple etiology and variable clinical presentation. We describe the case of a 25-day-old infant that presented with a tonic convulsion. Ultrasound examination showed tetraventricular hemorrhage. Magnetic resonance imaging (MRI) showed the presence of acute thrombosis of the deep and superficial venous systems associated to a hemorrhagic infarct of the left thalamus. Coagulation study revealed a deficit of protein C. Thrombosis of deep cerebral veins must be ruled out as a cause of a neonatal convulsive crisis. The presence of a hemorrhagic thalamic lesion supports the diagnosis of NCVT, which must in turn be confirmed by magnetic resonance angiography (MRA).

Neonatal Cerebral Sinovenous Thrombosis

The presentation, treatment, and outcome of neonatal cerebral sinovenous thrombosis (SVT) were studied in 42 children, using neurology clinic records (1986-2005) at Indiana University School of Medicine.

Aortic Arch Thrombosis in a Neonate With Heterozygous Carrier Status of Factor V Leiden Mutation

Neonatal spontaneous aortic arch thrombosis without an anatomical correlate is an extremely rare disorder of unknown etiology. A 1-day-old newborn was admitted with suspicion of the coarctation of the aorta. Angiography revealed congenital occluding thrombosis of the ascending aorta and the aortic arch. Surgery was considered impossible because of concomitant thrombosis of the inferior vena cava and the right renal vein. Thrombolysis with streptokinase and tissue plasminogen activator was attempted unsuccessfully. Heterozygous carrier status of the factor V Leiden mutation was diagnosed as a single prothrombotic risk factor. Congenital prothrombotic conditions including factor V Leiden carrier status may serve as risk factors for the development of spontaneous aortic arch thrombosis in neonates. In chronic organized thrombi thrombolytic therapy is likely to fail.

Calcified neonatal renal vein and vena caval thrombosis

We present an unusual case of an extensive venous thrombosis (involving the inferior vena cava, bilateral renal veins, gonadal vein and iliac veins) diagnosed in the neonatal period. The CT images revealed the typical diagnostic pattern.

Cerebral Sinovenous Thrombosis in the Neonate

There are few studies on neonatal cerebral sinovenous thrombosis (SVT). To describe the presentations, treatments, and outcomes of neonatal SVT and to assess infarction as a predictor of outcome. Retrospective chart study. A tertiary pediatric hospital in Indianapolis, Ind. Patients Forty-two children with neonatal SVT identified using International Classification of Diseases, Ninth Revision code searches from 1986 through June 2005 and review of neurology clinic records. None. Cognitive impairment, motor impairment, and epilepsy at last clinic visit. Gestational or delivery complications or risk factors and comorbid conditions such as dehydration, sepsis, and cardiac defects were common (gestational/delivery factors in 82% [31 of 38 with available maternal data]; comorbid conditions in 62% [26 of the 42]). Twenty-four (57%) presented with seizures. Twenty-five (60%) had infarcts, which were hemorrhagic in 22. Only 27 (64%) of 42 received prothrombotic evaluations; none had persistent deficiencies of protein C, protein S, or antithrombin III. Three (7%) received heparin sodium. All other children received only supportive care. One child died. Outcome data were available for 29 (71%) of the 41 survivors; of these, 23 (79%) had impairment(s). Two were known to be in early intervention, and no further information was available. Of the remaining 27, 16 (59%) had cognitive impairment, 18 (67%) had cerebral palsy, and 11 (41%) had epilepsy. Infarction was associated with the presence of later impairment (P = .03). The presentation of neonatal SVT is often nonspecific, the diagnosis can be difficult to make, treatment beyond supportive care is rarely used, and outcomes can be severe. Further work is needed to develop standardized guidelines for the evaluation and treatment of neonatal SVT.

Perinatal renal venous thrombosis: presenting renal length predicts outcome

Background: Renal venous thrombosis (RVT) is the most common form of venous thrombosis in neonates, causing both acute and long term kidney dysfunction. Historical predisposing factors include dehydration, maternal diabetes,...

Infantile Spasms as an Adverse Outcome of Neonatal Cortical Sinovenous Thrombosis

Cerebral sinovenous thrombosis is a rare but potentially serious condition often occurring in children with nonspecific presenting features. Much remains to be learned about the long-term outcome of infants with cerebral sinovenous thrombosis. We report a series of four patients taken from a prospective database of neonates with sinovenous thrombosis who subsequently developed infantile spasms, three with hypsarrythmia on electroencephalography and one with multiple independent spike foci. The first patient presented at 2 weeks of age with hypernatremia, dehydration, and seizures. He was found to have extensive thrombosis and hemorrhagic infarction of the right basal ganglia. The second patient presented at 5 weeks of life and was found to have sagittal sinus thrombosis with bilateral intracranial hemorrhage. The third patient presented with seizures on day 1 of life and was found to have venous thrombosis involving the torcular, extending into the sagittal sinus. The fourth patient presented at 3 weeks with lethargy and seizures. He was diagnosed with bacterial meningitis and also had extensive sinus thrombosis. All patients developed infantile spasms at ages 9, 7, 11, and 10 months, respectively. This is the first report in the English literature describing infantile spasms as a possible outcome of sinovenous thrombosis in early infancy.

Thrombosis in Infants and Children

During the last decade much progress has been made toward better understanding of the underlying reasons causing thromboembolism in children. A considerable number of acquired and hereditary thrombotic risk factors have been identified which may also have an impact on therapeutic decisions and prognosis concerning outcome and the risk of a second event. However, indications for therapeutic interventions, such as thrombolysis and prophylactic anticoagulation with respect to the different clinical conditions and their combination with other risk factors, are not yet well defined. The following article describes the causes, clinical presentation and management of thrombosis in neonates, infants and older children, focusing on the clinically most relevant conditions.