Publish in this journal
Journal Information
Vol. 91. Issue 1.
Pages 47-53 (01 July 2019)
Vol. 91. Issue 1.
Pages 47-53 (01 July 2019)
Scientific Letter
DOI: 10.1016/j.anpede.2018.08.007
Open Access
Thrombosis in the intensive care unit: Our experience in 10 years
Trombosis en cuidados críticos neonatales: nuestra experiencia en 10 años
Visits
91
María del Mar Alonso Montejo
Corresponding author
marialonsom9@gmail.com

Corresponding author.
, Lourdes Artacho González, María del Mar Serrano Martín
Sección de Unidad de Cuidados Críticos Neonatales, Hospital Regional Universitario de Málaga, Málaga, Spain
This item has received
91
Visits

Under a Creative Commons license
Article information
Full Text
Bibliography
Download PDF
Statistics
Tables (2)
Table 1. Patient characteristics and risk factors.
Table 2. Risk factors, location, treatment and outcome.
Show moreShow less
Full Text
Dear Editor:

In recent years there has been an increase in the frequency of diagnosis of neonatal thrombosis associated with the increased use of imaging tests1 and the increased survival of patients with complex conditions. The incidence is of 5 per 100,000 live births and 5 per 1000 patients admitted to an intensive care unit.2 Central catheterization is a risk factor found in 90% of episodes.3 At present, the treatment of thrombosis in newborns is based on adult guidelines4 and therefore a subject of controversy, with considerable heterogeneity in its management in clinical practice.

We describe the cases of 29 patients with thrombosis managed between 2008 and 2017 in a tertiary level neonatal intensive care unit (excluding postsurgical cardiac patients or patients treated with extracorporeal membrane oxygenation, which was delivered in a different unit of the hospital).

Table 1 presents the epidemiological characteristics and risk factors of the patients included in the study. The clinical manifestations that preceded diagnosis were heterogeneous, and 38.4% of the patients were asymptomatic. The diagnosis was based on the findings of Doppler ultrasound in 26 cases, and on the findings of magnetic resonance imaging (MRI) or computed tomography (CT) scans in the remaining 3. Table 2 presents the location of the thrombus, risk factors, treatment and outcome for each case.

Table 1.

Patient characteristics and risk factors.

Total (N=29) 
Gestational age (weeks, median)37 (33.5–39) 
Birth weight (g, median)2.915 (2.252–3.265) 
Sex (female)15 
Median age in days at diagnosis7 (3–14) 
Maternal risk factorsGestational diabetes 
Preeclampsia 
Chorioamnionitis 
Oligoamnios 
Maternal thrombophilia 
PROM 
IUGR 
Delivery risk factorsUrgent caesarean delivery 
Meconium aspiration syndrome 
Instrumental delivery 
Neonatal risk factorsCatheter  29 
Sepsis  17 
Respiratory distress syndrome  11 
Neonatal asphyxia 
Pulmonary hypertension 
Heart disease 
Erythrocytosis 
Hypothermia 
Corticoid therapy 
Other diseases 
Previous surgery 
Right-sided heart failure 
Enterocolitis 
Catheterization 
Thrombophilia 
Central catheter  29 
Central line malposition 

IUGR, intrauterine growth restriction; PROM, premature rupture of membranes.

Table 2.

Risk factors, location, treatment and outcome.

Patient  Sex/gestational age/birth weight  Catheter  Malposition  Risk factors  Thrombus location  Treatment/day initiated  Resolution of thrombosis  Complications  Sequelae/death 
M/41/4550  UVC  No  Heart defect (pulmonary atresia), surgery  Right femoral artery  LMWH/6  Lost to follow-up  Thrombocytopenia due to heparinanticoagulants  No 
M/40/-  UACUVC  NoYes  Asphyxia, PHT, RDS  Aorta and iliac artery  LMWH/4  Yes  No  No 
M/38/3870  UVC  Yes  Hyperinsulinism, asphyxia, sepsis, corticoids, maternal DM  Abdominal aorta  LMWH/19  Lost to followup  –  – 
F/41/3420  Percutaneous  No  Heart defect (Fallot), PDA stentcatheterization, asphyxia, sepsis, corticoids, maternal DM  Iliac and right femoral arteries  LMWH/16  Partial,collateral vessels  No  No 
M/39/3900  UVC  No  Sepsis, PHT  Iliac and femoral arteries  LMWH/7  Yes  No  No 
F/37/2940  Percutaneous  No  Madre: maternal MODY diabetes and factor V Leiden thrombophilia, RDS, sepsis  Bilateral renal artery  LMWH/UFH/rTPA/2  No  Choroid plexus bleeding  Renal failure 
F/34/2460  Percutaneous  No  Maternal DMprenatal: adrenal haemorrhage and thrombosis in the left hilum,erythrocytosis  Renal vein  LMWH/0  Yes  No  No 
M/40/3300  Percutaneous  No  Asphyxia, RDS, sepsis,corticoids  Cerebral sinuses  LMWH/20  Yes, partial  Severe gastrointestinal bleeding: transfusion, octreotide and temporary discontinuation of heparin  No 
M/30/1320  UAC, UVC, percutaneous  No  Sepsis  Superior vena cava  LMWH/22  Lost to follow-up  Thrombocytopenia  No 
10  F/39/3720  UVC, percutaneous  YesNo  Hyperinsulinism,corticoids  RA 12×13mm  LMWH/12  Yes, discontinuation of heparin in 8 weeks  No  No 
11  F/38/3020  UVCUAC, percutaneous  Yes (portal)No  Asphyxia, hypothermia,RDS, corticoids  Cerebral sinuses  LMWH/10  No new imaging tests  No  No 
12  F/26/740  UVC, percutaneous  Yes (RA)  NRFS  RA 7×8mm  LMWH/3  No  Probable PE  Death due to PE 
13  F/35/2230  UVCUAC, percutaneous  Yes (RA)NoNo  Asphyxia, hypothermia, sepsis,oligoamnios, IUGR  Cerebral sinuses  LMWH/17  Yes  No  No 
14  F/28/1140  UVC, percutaneous  Yes (RA)No  Sepsis  RA 19×10mm  Watchful waiting(intraventricular haemorrhage grade III)  –  Probable PE  Death due to PE 
15  M/38/2890  UVC, percutaneous  NoNo  Maternal DMSepsis  Cerebral sinuses  LMWH/9  Yes, partial  No  NoWithholding of treatment (ventilator-dependent nemaline myopathy) 
16  F/40/2940  UVC, UAC, percutaneous  YesNoNo  Asphyxia, hypothermia  Portal  LMWH/8  Yes  No  No 
17  F/36/2550  UVC, percutaneous  NoNo  Sepsis, erythrocytosisSteinert disease,  Cerebral sinuses  LMWH/14  Yes  No  No 
18  F/39/3290  UVC, percutaneous  NoNo  congenital surfactant deficiency, left ventricular hypertrophy, right-side heart failureRDS, sepsis  Portal and umbilical  LMWH/11  Yes, partial  No  No 
19  M/34/2450  UVC, UAC  No  Heart defect (transposition of great vessels), Rashkind atrial septostomyRDS  Right femoral vein  Watchful waiting, favourable outcome  Lost to follow-up  –  – 
20  F/38/2600  Percutaneous  No  –  Renal vein  Watchful waiting, progression of thrombosis  Yes    Renal atrophy 
21  F/36/3080  UVC, percutaneous  NoNo  Dehydration,sepsis  Umbilical vein  Watchful waiting  Lost to follow-up  –  – 
22  M/39/3040  CVC  No  Oligoamnios, sepsis  Inferior vena cava  UFH→LMWH/1  Yes  No  Renal atrophy 
23  M/33/2990  UVC  No  Maternal DM, preeclampsiaRDS, sepsis, corticoids  Right renal vein  Watchful waiting, coagulopathy  –  –  Renal failure, multipole organ failure, CA, death 
24  M/37/2370  UVC  No  Maternal DM, PROM,erythrocytosis  Umbilical vein  Watchful waiting,asymptomatic  Yes  –  No 
25  M/31/1532  UVC  No  Heart defect (ASD),RDS, erythrocytosis, sepsis,NEC, gastrointestinal surgery  Brachiocephalic and jugular arteries  LMWH/120  No,collateral vessels  No  No 
26  M/31/2320  Percutaneous  No  Severe oligoamnios,RDS  Bilateral renal vein  LMWH/4  Yes, partial,renal disease  No  Yes, grade 2 CKD grade II 
27  M/37/2135  UVC, percutaneous  NoYes  Sepsis, NEC, IUGR  Portal  LMWH/14  Yes  No  Cavernomatosis and PHT 
28  F/40/3190  UVCUAC, percutaneous  Yes (portal)NoYes  PROM, asphyxia, hypothermia,RDS, sepsis  Portal  LMWH/7  –  No  NoWithholding of treatment 
29  F/31/1790  UVC, percutaneous  NoNo  RDS, sepsis, erythrocytosis  Portal  Watchful waiting, coagulopathy  –  –  Refractory pulmonary haemorrhage -hypoxaemia, CA, death (familial intrahepatic cholestasis type 2) 

ASD, atrial septal defect; CA, cardiac arrest; CKD, chronic kidney disease; DM, diabetes mellitus; IUGR, intrauterine growth restriction; LMWH: low molecular weight heparin (150IU/kg/day; monitored by measurement of anti-factor Xa levels [target, 0.35–0.7IU/mL], first at 4 days and after weekly or every 15 days depending on measured levels); NEC, necrotising enterocolitis; NRFS, non-reassuring foetal status; PHT, pulmonary hypertension; PROM, premature rupture of membranes; rTPA, recombinant tissue plasminogen activator (0.1–0.5mg/kg/h twice daily for 7 days); PE, pulmonary embolism; RA, right atrium; RDS, respiratory distress syndrome; UAC, umbilical artery catheter; UFH, unfractionated heparin (14–28IU/kg/h); UVC, umbilical vein catheter.

A total of 6 patients died (20%): 2 (cases 11 and 13) as a direct result of thrombosis in the right atrium, with a clinical presentation compatible with pulmonary embolism. A third patient (case 23) died of hypoxic-ischaemic encephalopathy with multiple organ failure in the context of right renal vein thrombosis, with no other relevant findings in the autopsy. The remaining patients died of causes secondary to other diseases, such as pulmonary haemorrhage (case 29) or withholding of life-sustaining treatment in the context of other diseases (cases 15 and 28).

Of the 4 patients that had life- or organ-threatening thrombosis (cases 6, 10, 12 and 14), 2 died. Only 1 had a favourable outcome after treatment with bemiparin of a small atrial thrombus, which resolved in 8 weeks. The patient with bilateral renal artery thrombosis (case 6) was initially treated with fibrinolytic drugs, but the treatment had to be discontinued due to haemorrhage of the choroid plexus, after which she developed end-stage renal disease.

Five patients underwent an evaluation of thrombophilia, and abnormalities were found in 2 (factor V Leiden and factor II and XII, cases 6 and 26).

In the management of neonatal thrombosis, the morbidity and mortality are determined to a great extent by the location of the thrombus. The outcome depends on the optimal diagnosis and management, and therefore in patients at risk, if there is suspicion based on the clinical presentation or laboratory results (persistent thrombocytopenia), imaging tests should be requested at an early stage (Doppler ultrasound, CT angiogram or magnetic resonance angiogram), and an angiogram should be performed in cases with an uncertain diagnosis. We recommend against the D-dimer test in newborns.

The treatment of neonatal thrombosis poses dilemmas that are a source of controversy due to the risk of bleeding in this population, and there is considerable variability in its management between health providers and facilities. The clinical practice guidelines on antithrombotic therapy in newborns and children4 indicate that in cases of life- or organ-threatening thrombosis, and in the absence of absolute contraindications (surgery or central nervous system ischaemia, active bleeding, invasive procedures or seizures in the past 48–72h), initiation of thrombolytic therapy should be considered taking into account the size and location of the thrombus (such as: diameter>2cm and/or mobile right atrial thrombosis). The risk–benefit assessment should be individualised. There are different schemes for thrombolytic therapy with recombinant tissue plasminogen activator (rtPA), and at present there is no evidence supporting the superiority of any of them.4

If there is no risk of patient or organ death or thrombolytic therapy is contraindicated, treatment with an anticoagulant agent treatment should be initiated (low-molecular weight or unfractionated heparin)3 in patients who are symptomatic (hypertension, change in limb colour, persistent tachycardia, …), while in patients who are asymptomatic and in whom thrombosis was a chance finding, the decision whether to maintain a watchful waiting approach should be made on a case-by-case basis.

We recommend that the follow-up of patients with thrombosis, especially in cases with a related family history, of great severity (purpura fulminans) or in the absence of risk factors, include an investigation of thrombophilia.2

Although the reported evidence on the subject is limited, given the high morbidity and mortality associated with thrombosis in critical locations (50% of our sample) and that the reviewed literature offers encouraging data regarding the use of fibrinolytic agents (even in patients born preterm),5,6 early use of thrombolytic therapy should be considered in life- or organ-threatening cases as long as the hospital has the necessary resources and experienced staff, always with an individualised risk–benefit assessment.

Our study was retrospective, and it is important to take into account the limitations intrinsic to this type of design.

References
[1]
A. Veldman, M.F. Nold, I. Michel-Bechnke.
Thrombosis in the critically ill neonate: incidence, diagnosis, and management.
Vasc Health Risk Manag, 4 (2008), pp. 1337-1348
[2]
A. Matthew, M.D. Saxonhouse.
Thrombosis in the neonatal intensive care unit.
Clin Perinatol, 42 (2015), pp. 651-673
[3]
V. Baccieoni, M. Attie, H. Donato.
Trombosis en el recién nacido.
Arch Argent Pediatr, 114 (2016), pp. 159-166
[4]
P. Monagle, A. Chan, N. Goldenberg, R. Ichord, J. Journeycake, U. Nowak-Göhl, et al.
Antithrombotic therapy in neonates and children: antithrombotic therapy and prevention of thrombosis.
[5]
P. Álvarez, L. Verdugo, K. Carvajal, G. Múlhausen, P. Ríos, V. Rodriguez.
Activador del plasminógeno tisular recombinante en el manejo de trombos cardiacos en recién nacidos.
Rev Chil Pediatr, 86 (2015), pp. 194-199
[6]
F. Ferrari, F. Vagnarelli, G. Gargano, M.F. Roversi, O. Biagioni, A. Ranzi, et al.
Early intracardiac thrombosis in preterm infants and thrombolysis with recombinant tissue type plasminogen activator.
Arch Dis Child Fetal Neonatal Ed, 85 (2001), pp. F66-F69

Please cite this article as: Alonso Montejo MdM, Artacho González L, Serrano Martín MdM. Trombosis en cuidados críticos neonatales: nuestra experiencia en 10 años. An Pediatr (Barc). 2019;91:47–53.

Copyright © 2019. Asociación Española de Pediatría
Idiomas
Anales de Pediatría (English Edition)

Subscribe to our newsletter

Article options
Tools
es en

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

es en
Política de cookies Cookies policy
Utilizamos cookies propias y de terceros para mejorar nuestros servicios y mostrarle publicidad relacionada con sus preferencias mediante el análisis de sus hábitos de navegación. Si continua navegando, consideramos que acepta su uso. Puede cambiar la configuración u obtener más información aquí. To improve our services and products, we use "cookies" (own or third parties authorized) to show advertising related to client preferences through the analyses of navigation customer behavior. Continuing navigation will be considered as acceptance of this use. You can change the settings or obtain more information by clicking here.