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Department of Hematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada
Department of Hematology/Oncology, McMaster University, Hamilton, Ontario, Canada
s u m m a r y
Keywords:
Anticoagulation
Liver lobe atrophy
Neonate
Portal hypertension
Portal vein thrombosis
Neonatal portal vein thrombosis (PVT) is an increasingly recognized event. Patients are generally
asymptomatic in the neonatal period. The diagnosis is made with Doppler ultrasound. Umbilical catheterization, exchange transfusion and sepsis are risk factors for neonatal PVT. Thrombophilia is possibly
a contributing risk factor. Although there are potential serious acute complications such as hepatic
necrosis, the outcome is good in the majority of cases, followed up to 8 years of age. Thrombus resolution
occurs in 30e70% in days to months. Liver lobe atrophy may occur following PVT, and does not appear to
be associated with any impairment of liver function. Non-occlusive thrombosis is more likely to resolve
than non-occlusive thrombosis. A subset of patients without resolution is at risk for developing portal
hypertension over the next decade of life. There are no current dening features present during the
neonatal period to enable identication of neonates at risk for portal hypertension. There is no evidence
that anticoagulation therapy improves time to resolution or decreases the likelihood of portal hypertension. Anticoagulation therapy may be considered. A management algorithm is proposed.
2011 Elsevier Ltd. All rights reserved.
1. Introduction
Neonatal portal vein thrombosis (PVT) has been described as
a rare event, but is becoming more commonly recognized. Estimates range from 1 in 100,000 live births1 to 36 per 1000 neonatal
intensive care unit admissions.2 Because portal venous thrombosis
rarely causes clinical problems during the neonatal period, historically the majority of cases remained unrecognized in the neonatal
period and were found later in childhood.3,4 This led to the
supposition that neonatal PVT was as described by Thompson and
Sherlock: exceedingly rare.5
By contrast with the reported rarity in the neonatal setting, PVT is
the major cause of extrahepatic portal hypertension and gastrointestinal bleeding in children.3 Prehepatic or extrahepatic portal
hypertension is most commonly the result of an organized
thrombus in the portal vein. Portal vein brosis, stenosis, or web
may also lead to elevations in portal venous pressure.6 Occlusion of
the portal vein associated with small periportal collaterals is known
as cavernous transformation of the portal vein (CTPV).7
The etiology of neonatal PVT is different from that in children and
adults. In adults PVT is most frequently secondary to cirrhosis.8 In
older children, PVT is related to liver transplantation, intra* Corresponding author. Department of Hematology/Oncology, The Hospital for
Sick Children, 555 University Ave., Toronto, Ontario M5G 1X8, Canada. Tel.: 1 416
813 8997; fax: 1 416 813 5327.
E-mail address: suzan.williams@sickkids.ca (S. Williams).
1744-165X/$ e see front matter 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.siny.2011.08.005
abdominal sepsis, splenectomy, sickle cell anemia, and antiphospholipid antibodies.8e14 In w50% of children with PVT, an
underlying etiology is not identied.10,15 PVT in neonates commonly
occurs secondary to the placement of an umbilical vein catheter
(UVC), with or without infection.16e18
2. Historical aspects
Historically, the etiology of portal vein occlusion in children has
been attributed to a variety of causes from congenital malformations
to thrombosis associated with infection and most recently to
thrombosis as a potential complication from trauma or vessel
catheterization. Prenatal onset of PVT and in association with
umbilical vein thrombosis has also been reported.19e21
Cavernomatous transformation of the portal vein was historically described as a congenital or tumour-associated formation. In
initial reports, a congenital malformation22 or hamartoma23 were
presumed.
In 1928, Klemperer reviewed previously reported cases and
suggested that thrombosis was responsible for the changes in the
portal vein.24 Wallgren in 1927 had postulated PVT as a complication of previous intra-abdominal infection, citing umbilical sepsis25
and appendicitis as possible causes. The possibility of umbilical
infection without sepsis having more disseminated complications
was described in a case of severe umbilical infection with cellulitis
of the anterior abdominal wall in 1957.26 Neonatal sepsis and
330
S. Williams, A.K.C. Chan / Seminars in Fetal & Neonatal Medicine 16 (2011) 329e339
Year
Total
patients
Septicemia
Umbilical
sepsis
PVT
Thompson et al.5
Yadav et al.46
Schwartz et al.17
Guimaraes et al.47
Kim et al.37
Sakha et al.55
Gharehbaghi et al.54
1964
1993
1997
1998
2001
2007
2011
493 (470)a
47
173 (100)a
40
100
50
164
51 (10%)
7 (15%)
e
e
5 (5%)
11 (22%)
10 (6%)
37 (8%)b
4 (8.5%)
e
e
e
e
2 (1%)c
0
0
1 (1%)
0
43 (43%)
17 (34%)
5 (3%)
a
b
c
Patients followed.
Umbilical infections.
Peri-umbilical erythema.
Fig. 1. Anatomy of neonatal portal vein. RPV, right portal vein; RHV, right hepatic vein;
IVC, inferior vena cava; LHV, left hepatic vein; LPV, left portal vein; SV, splenic vein;
SMV, superior mesenteric vein; PV, portal vein (Published with permission from Kim et
al.110).
Year
UVC (n)
PVT N (%)
Time to image
Thompson et al.5
Yadav et al.46
1964
1993
493 (470)a
47
0b
0
Schwartz et al.17
Guimaraes et al.47
Kim et al.37
1997
1998
2001
173 (100)a
40
43
1 (0.6%)
0
43 (43%)
Sakha et al.55
2007
50
17 (34%)
Turebylu et al.56
2007
28
2 (7%)c
Gharehbaghi et al.54
2011
164
5 (3%)
School age
22 newborns:
within 4e8 weeks,
q3 months to age
12 months, 24 months.
25 children at age
1e5 years
3 days to 5 months
8e9 years
Within 1 week of UVC
q2e4 days till
UVC removal
q2e7 days till
resolution
1e2 weeks after
UVC removal
q1e2 months until
clot resolution
3, 5e7 days post UVC
Weekly while UVC
in place
3 days post UVC
24e48 h of UVC
48e72 h post
UVC removal
Weekly till discharge
or resolution
Patients followed.
Three children died and had suppurative thrombophlebitis in umbilical vein,
extending into ductus venosus, with no specic mention of portal vein on
postmortem.
c
Additional 4 (14%) had inferior vena cava clots.
b
S. Williams, A.K.C. Chan / Seminars in Fetal & Neonatal Medicine 16 (2011) 329e339
331
332
Table 3
Neonatal and childhood portal vein thrombosis: radiologic and clinical outcome.
Year
Diagnosis
Treatment
Alvares et al.3
1983
108 (1 months
to 15 years)
104 AG
4 US
3 VL
1 MS
76 PS
Schwartz et al.17
Kim et al.37
1997
2001
1
43 neo
US
US
2006
US
Morag et al.
(e)UVC
Complete
resolution (CR)
100%
18/36 (50%)
2/36 (6%)
81/133 (61%)
16/133 (12%)
Turebylu et al.56
Sakha et al.55
2007
2007
Demirel et al.71
2009
Morag et al.32
2011
70d
US
14/37 (38%)
normal
Gharehbaghi et al.54
2011
5 occ
US
3/5 (60%)
US
US
US
None
ACT (LMWH
/UFH)
No change
Extension or
recurrence
Time to
CR/PR
LLA
PHTN
Death
2a
133
128/133 neo
5/133 inf
5
17 neo
16 nocc
1 occ
15 neo
ACT 59/133
(44%)
Partial
resolution (PR)
3/5 (60%)
13/13 (100%)
11/36
(30%)
5/36 (9%)
6 months
2e23 days
(e)UVC
2e626 days
mean: 63
median: 25
3e6 weeks
2e5 months
1/36 (3%)
30/133
(22.5%)
6/133 (4.5%)
22/133 (16%)b
NA
NA
2/5 (40%)
0
13/15 (87%)c
2/15 (13%)a
20/37 (54%)
2/20 (10%)
PHTN
3e6 weeks
2/37 (5%)
6/133 prior PHTN
2/6 (33%) CR
1/6 (17%) transplante
1/6 (17%) lost
2/6 (33%) PCS
2/5 (40%)
LLA, liver lobe atrophy; PHTN, portal hypertension; AG, angiogram; US, ultrasound; VL, variceal ligation or gastric devascularization; MS, mesocaval shunt; PS, portosystemic shunt surgery; neo, neonates; inf, infants; PCS,
portacaval shunt; lost, lost to follow-up; (e)UVC, umbilical venous catheter removal; nocc, non-occlusive; occ, occlusive.
a
Due to other causes.
b
25/133 (22.5%) lost to follow-up.
c
Described as recovered.
d
Follow-up at 2e8 years from prior cohort: 12/133 primary liver pathology, 22/133 deaths before 2 years, 29/99 (29%) lost to follow-up.
e
Patient with primary liver disease.
S. Williams, A.K.C. Chan / Seminars in Fetal & Neonatal Medicine 16 (2011) 329e339
Study
S. Williams, A.K.C. Chan / Seminars in Fetal & Neonatal Medicine 16 (2011) 329e339
portal sinus can lead to adjacent liver necrosis, found on postmortem examination, with risk factors for necrosis including
placement of the umbilical catheter in the portal vein, infusion of
alkaline solution, sodium bicarbonate via the catheter, and
thrombocytopenia.63 Cerebral infarct resulting from paradoxical
emboli, in which emboli from the PVT passing through the ductus
venosus and foramen ovale into systemic circulation, has been
reported.64 Hepatic hematoma with PVT related to malpositioned
umbilical venous catheter has been reported.49 Bleeding diathesis
with hemorrhagic ascites, massive intrapulmonary bleeding, and
subsequent death in diffuse intrahepatic PVT with marked hepatic
necrosis conrmed by postmortem has been documented.20
5.1. Resolution
The long term sequelae and clinical importance of thrombosis
detected on ultrasound in asymptomatic neonates are not fully
understood. The spontaneous regression of catheter-related
thrombi detected on ultrasound has been reported.17,65 In fact,
early spontaneous resolution has been postulated as a reason why
PVT was diagnosed only relatively rarely in the clinical setting of the
neonatal intensive care unit.3,17,37 The single detected PVT in the
Schwartz study had detection at 2 weeks and resolution at 6
months.17 In the ve PVT detected at 3e12 days in the Gharehbaghi
et al. study, three (60%) resolved by 3e6 weeks, whereas the two
other patients died before a second ultrasound.54 Recanalization
(partial or complete resolution) occurs more frequently in cases
with partial thrombi than in cases with occlusive thrombi. Kim et al.
found a statistically signicant relationship between the initial size
of the thrombus (occlusive versus non-occlusive) and clot resolution. Resolution occurred in 70% of neonates with non-occlusive
clots and 31% of neonates with occlusive clots. The time to detection of resolution after the removal of the catheter was at a mean of
10 days with a range of 2e23 days.37 There were similar ndings in
the Morag et al. study, in which there was a higher resolution rate in
non-occlusive versus occlusive clots with 77% resolution for
non-occlusive clots and 48% for non-occlusive clots; mean time
detected to resolution of the thrombus was 63 days (range: 2e626
days; median: 25 days). Although there was no association of
outcome with presence of an umbilical venous catheter, in the
subset of patients with umbilical venous catheters, there were
higher resolution rates in infants with appropriate placement of
umbilical venous catheters compared to low or intrahepatic
placements.2
5.2. Portal hypertension and cavernoma
If the PVT does not resolve, there may be long term implications.
It may transform into a cavernoma, with dilated pancreaticoduodenal and prebiliary veins, secondary to portal hypertension.33,37,46,47,66 Esophageal variceal bleeding, splenomegaly and
growth retardation are the most common clinical features in children with portal hypertension. Alveraz et al. found that portal
hypertension was diagnosed at a mean of 5.7 years after the acute
event. Eighty percent of patients with portal hypertension present
within the rst 3 years of life.3,33,41,67e69 Portal cavernomas and
portal hypertension were not seen in neonates with PVT followed
for 2e73 days (median: 8 days).37 Portal hypertension occurred in
(6/133) 4.5% followed for a median of 79 days (range: 1e1814 days).2
In the follow-up study of a subset of 70 of the neonatal cohort at
a median age of 5 years (range: 2e8 years), two children with portal
hypertension diagnosed during neonatal period required portacaval
shunting.32
However, portal hypertension appears to be uncommon
following neonatal PVT. This may in part be due to the predominant
333
334
S. Williams, A.K.C. Chan / Seminars in Fetal & Neonatal Medicine 16 (2011) 329e339
Table 4
Thrombophilia and paediatric portal vein thrombosis.
Study
FVL
PTG
Y PC
Y PS
Y AT
MTHFR/[
Homocys
Combined/other
OR (95% CI)
Heller et al.1
Demirel et al.71
24
16
4 (17%)
0
0
0
1 (4%)
0
0
0
1 (4%)
0
1 (4%)
0
Morag et al.2
Morag et al.32
El-Karaksy et al.72
40
25
40
1 (2.5%)
2 (8%)
11 (27.5%)
0
0
5 (12.5%)
0
NP
11 (27.5%)
0
3 (12%)
0
1 (2.5%)
1 (4%)
0
NP
NP
NP
ACLA 2 (8%)
PTG MTHFR 1 (7%)
[ FVIII 0 (0%)
[ FVIII 11 (27.5%)
6 for FVL
Pietrobattist et al.77
5 (12.5%)
Y PC Y AT def 1 (2.5%)
Y PC FVL APCR 1 (2.5%)
Y PC PTG 1 (2.5%)
FVL APCR PTG 2 (5%)
31
2 (7%)
3 (10%)
4 (13%)
4 (13%)
NP
Pinto et al.73
14
1 (7%)
6 (43%)
3 (21%)
1 (7%)
UttenreutherFischer et al.75
Dubuisson et al.74
Seixas et al.108
Schobess et al.109
23
2 (9%)
NP
NP
NP
NP
16 (68%)
(13% homo)
4 hetero (28%)
3 homo (21%)
NP
20
20
9
NP
0
2 (22%)
NP
NP
NP
9 (45%)
NP
NP
13 (65%)
NP
NP
10 (50%)
NP
NP
NP
NP
NP
FVL, factor V Leiden; PTG, prothrombin gene mutation; PC, protein C; PS, protein S; AT, antithrombin deciency; FVIII, factor 8; MTHFR, methylene tetrahydrofolate reductase
variant mutation; Homocys, homocysteine; APCR, activated protein C resistance; ACLA, anticardiolipin antibody; NP, not performed or not provided; homo, homozygous
mutation; hetero, heterozygous mutation.
Table 5
Clinical presentation of neonatal portal vein thrombosis.
Study
Year
Signs
Symptoms
Kim et al.37
Morag et al.2
2001
2006
None
None
55
2007
43 neonates
128 neonates
5 infants
17 neonates
16 nocc
1 occ
15 neonates
Sakha et al.
Demirel et al.71
2009
Gharehbaghi et al.54
2011
Laboratory tests
Thrombocytopenia
26/133 (19.5%)
Sepsis 11 (65%)
Hepatosplenomegaly
2 (13%)
5 neonates
5 occ
nocc, non-occlusive; occ, occlusive; AST, aspartate aminotransferase; ALT, alanine aminotransferase.
S. Williams, A.K.C. Chan / Seminars in Fetal & Neonatal Medicine 16 (2011) 329e339
335
Table 6
Clinical presentation of childhood portal vein thrombosis.
Study
Year
Patients
Symptoms
Signs
Laboratory tests
Alvares et al.3
1983
108 children
Mean age:
5 years 7 months
Range: 1 month
to 15 years
86 GI bleeds (80%)
Hematemesis 58 (53%)
Melena 19 (17.5%)
Hemorrhoid
bleeding 5 (4.6%)
Diarrhea 5 (4.6%)
Abdominal
distension 5 (4.6%)
Splenectomy 5 (4.6%)
Abdominal pain 2 (2%)
El-Karaksy et al.72
2004
40 children
PHTN 2
to PVT
Splenomegaly 35 (87.5%)
Splenectomy 5 (12.5%)
Incidental splenomegaly
3 (7.5%)
Pietrobattist et al.77
2010
31 children
Peter et al.107
2003
86 children
EHPVO
Ascites 2 (2.3%)
Splenomegaly 11 (12.8%)
Morag et al.32
2011
70 children
Median age:
55 months
Range:
24e96 months
Hematemesis melena
15 (37.5%)
Hematemesis 7 (17.5%)
Melena 1 (2.5%)
Abdominal distension
11 (27.5%)
Abdominal pain 3 (7.5%)
Neonatal sepsis 2 (10%)
Umbilical sepsis 3 (5%)
Umbilical sepsis (6%)
Gastroenteritis and
Dehydration (6%)
Family history of
VTE (3%)
Parental consanguinity
(1%)
UGI bleeding
53 (61.6%)
Jaundice
Splenomegaly 3/37 (8%)
GI, gastrointestinal; PHTN, portal hypertension; PVT, portal vein thrombosis; UGI, upper gastrointestinal; VTE, venous thromboembolism; EHPVO, extrahepatic portal vein
occlusion.
336
S. Williams, A.K.C. Chan / Seminars in Fetal & Neonatal Medicine 16 (2011) 329e339
8. Treatment
8.1. Impact of anticoagulation
The role of anticoagulation in PVT management is unclear. Given
that there is often rapid resolution e and even in the absence of
resolution, there may be no clinical sequelae from the liver lobe
atrophy e the question of whether anticoagulation therapy would
lead to a decrease in the rates of portal hypertension in childhood
remains unanswered.
There is an absence of prospective data on anticoagulation in the
literature. Multiple strategies have been reported in the literature
from observation, anticoagulation, and thrombolysis. In the retrospective Morag et al. study with reported resolution rates of 81/133
(61%) with complete or partial resolution and 16/133 (12%) with no
change, and no infants with extension described, anticoagulation
treatment was given to 59 infants. The authors describe no association of outcome with the use of anticoagulation. The indications
for anticoagulation treatment included the presence of a second,
occlusive thrombus with liver parenchymal changes or involving
two branches of the portal vein, post cardiac surgery. Dosages and
lengths of treatment varied signicantly.2
8.2. Absence of guidelines
There are no evidence-based guidelines on treatment of
neonatal PVT. The American College of Chest Physicians have been
unable to develop specic guidelines due to insufcient data. The
literature on neonatal PVT consists largely of case reports, and the
infrequency of the diagnosis hinders obtaining evidence that would
permit informed pediatric guidelines for therapy. Differences in
etiology and pathophysiology reduce the usefulness of the
extrapolation of therapeutic guidelines for adults with PVT to
children, much less neonates.87
Although there are insufcient data to make strong recommendations regarding anticoagulation therapy for neonatal PVT,
the options include conventional anticoagulation therapy in ageappropriate doses, short term anticoagulation therapy, or close
monitoring of the thrombus with objective tests and the use of
anticoagulation therapy if thrombus extension occurs. The treatment in each neonate should be individualized with consideration
of the risk:benet ratio. Importantly, there is no current evidence
that anticoagulation therapy would lead to improved outcome
following neonatal PVT, namely reduction in the incidence of portal
hypertension.
8.3. Current recommendations for anticoagulation in neonates
There are several Grade 2C or weak treatment recommendations based on low quality evidence.88 The guiding principles in
light of the lack of evidence would be to avoid anticoagulation if
possible and treat for the minimum duration possible. Anticoagulation treatment with unfractionated heparin (UFH) or low
molecular weight heparin (LMWH) can be initiated. Alternatively,
radiographic monitoring with anticoagulation therapy if extension
occurs can be considered. Initial anticoagulation would be appropriate in the absence of contraindications such as bleeding, coagulopathy, intracranial hemorrhage or cerebral infarct. If
anticoagulation is selected, initial administration would be in the
form of UFH or LMWH, and subsequent LMWH for 10 days to 3
months.87
If no therapy is chosen, interval imaging to rule out an extending
thrombosis would be appropriate. Imaging at the end of the initial
phase of therapy would be prudent to decide on need for further
therapy. Imaging should be repeated after completion of anticoagulation therapy to rule out extension when off therapy.
Treatment of symptomatic acute PVT, extending to the main
portal vein, by means of regional streptokinase infusion has been
reported.89 However, aggressive therapy is not likely warranted in
the majority of cases. Thrombolytic therapy should be reserved for
major vessel occlusion with organ compromise. In contrast to the
ischemic symptoms caused by thromboembolism of the arteries,
PVT seldom causes clinical problems during the neonatal period,
may resolve without any intervention, and even unresolved
thrombosis is expected to remain silent if it does not propagate into
other branches. Therefore unless the PVT extends into the adjacent
vessels e inferior vena cava, renal veins or right atrium e with
clinical symptoms, the risk of thrombolysis likely outweighs the
benet. In order to ensure adequate plasminogen to maximize
efcacy of thrombolytic therapy, supplementation with plasminogen via the use of fresh frozen plasma should occur immediately
prior to thrombolysis.
8.4. Considerations for anticoagulation
After initial treatment with UFH or LMWH, vitamin K antagonists (VKA) with a target INR of 2e3 could theoretically be used to
continue anticoagulation therapy. However, the use of warfarin in
the neonatal period is problematic. Formula-fed infants will receive
large amounts of vitamin K, and will be warfarin resistant. Dosing
becomes difcult as there is no commercially available liquid
formulation of warfarin.90 Given the anticipated difculties, anticoagulation with warfarin would not be recommended in the
neonatal period.
LMWH may be preferable to UFH if anticoagulation therapy is
used to treat neonatal PVT, given the predictable pharmacokinetics,
reduced monitoring requirements, and possibly decreased rate of
major bleeding. In a randomized, controlled trial of therapeutic
anticoagulation in children, LMWH therapy was compared with
UFH and VKA for the treatment of venous thromboembolic events
in children. There was a major bleeding rate of 12.5% in the UFH/
VKA versus 5.6% in the LMWH arm.91 A major bleeding rate of 0.7%
of children treated with the low molecular weight heparin, enoxaparin, has been reported.92 The rate of major bleeding in children
aged <3 months receiving enoxaparin has been reported as 3%.93
Neonates have an increased dose requirement compared to
older infants and children. Increased dose requirement in neonates
is multifactorial. Anticoagulant proteins are decreased in the
neonate when compared to adult levels.94,95 The levels of natural
anticoagulants such as antithrombin and protein C are decreased to
35e50% of adult levels during the neonatal period.95,96 Neonates
also have an increased volume of distribution which will accentuate
the volume of distribution for hydrophilic drugs such as the
commonly used low molecular weight heparin, enoxaparin.97
Preterm infants tend also to have higher dose requirements than
term infants.98,99 Therefore, a higher low molecular weight heparin
dosing than in older children should be considered to facilitate
faster time to therapeutic levels, and to decrease the number of
venipunctures required for monitoring.100
Apart from bleeding, there are other potential side-effects of
anticoagulation. Heparin-induced thrombocytopenia (HIT) is an
immune-mediated thrombocytopenia accompanied by a paradoxical prothrombotic state, occurring after heparin exposure.101 The
incidence of HIT in pediatric intensive care units is 1.5e2.3%.102 The
incidence of HIT in neonates is reportedly lower. In 108 neonates
receiving heparin for more than 5 days, none developed HIT.103 HIT
occurs less frequently following LMWH exposure than UFH exposure.104 However, HIT has been reported in children following the
use of enoxaparin.105 Heparin use has also been associated with
S. Williams, A.K.C. Chan / Seminars in Fetal & Neonatal Medicine 16 (2011) 329e339
337
PVT
Remove UVC,
HUS, INR,
aPTT, FBN,
PLT, LFTs
Coagulopathy
No Coagulopathy
No ACT
ACT UFH
US @ 5-7 days
Extension
ACT LMWH
US @ 10 days
Resolution
Stable/smaller
on
3 images
Resolution
Stable/Smaller
Stop ACT
ACT X 3 mos
LMWH
US @ 5-7 days
No PVT
Extension
IVC/RA/RV
with
symptoms
Consider tPA
Extension
PVT
338
S. Williams, A.K.C. Chan / Seminars in Fetal & Neonatal Medicine 16 (2011) 329e339
Practice points
Neonatal PVT is increasingly recognized.
Neonatal PVT may have no signs or symptoms.
Diagnosis of neonatal PVT is via colour Doppler
ultrasound.
Umbilical venous catheters and sepsis are risk factors
for neonatal PVT.
60e70% of neonatal PVT may have spontaneous resolution in the neonatal period.
Non-occlusive PVT are more likely to resolve than
occlusive PVT.
Non-resolving neonatal PVT are associated with liver
lobe atrophy, which may be of no clinical significance.
A small subset of neonates with PVT will develop portal
hypertension in childhood.
The role of anticoagulation in the management of
neonatal PVT is unclear.
The role of thrombophilia in neonatal PVT is unclear.
Conict of interest statement
None declared.
Funding sources
None.
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