3. DISCUSSION
Over the last few decades, the incidence of thromboembolic events in
children, particularly among the critically ill neonatal population, has
significantly
increased(1).
Estimates of neonatal thrombosis range from 1 in 100,000 live births1 to
36 per 1000 neonatal intensive care unit
admissions(2,4–6).
Various studies showed incidence of venous thrombosis more than arterial
thrombosis(7–9). The
neonatal population has a unique risk factor profile for the development
of thrombosis secondary to the contribution of maternal and peri
delivery risk factors, not present in other pediatric
populations(1,2). The
most common neonatal-related factors include the presence of a CVC and
the development of infection/sepsis or other inflammatory
conditions(10). The
maternal risk factor includes, infection, underlying comorbidities such
as metabolic syndrome, diabetes, pre-eclampsia or hypertension,
inherited or acquired thrombophilias and placental thrombosis or
abruption. Emergency c- section, PROM, PPROM, perinatal asphyxia,
meconium aspiration, steroid use and bradycardia are peri delivery risk
factors associated with neonatal
thrombosis(2).
Neonatal hemostatic system is different from the one of the older
children and
adults(11,12).
Coagulation proteins do not cross the placenta but are synthesized in
the fetus from an early stage and levels of antithrombin, heparin
cofactor II and protein C and S are low at
birth(1).
Additionally, infection and sepsis increases the risk of thrombosis
through several mechanisms such as direct endothelial dysfunction,
activation of coagulation factor and consumption of anticoagulant
proteins and downregulation of the protein c
system,(13).
Thromboembolic events in neonates are associated with significant
morbidity and mortality, including the loss of vital vascular access,
increase bleeding risk secondary to the use of anticoagulation therapy,
and the development of long-term complications such as limb loss in
arterial thrombosis, portal hypertension, renal dysfunction, and the
post-thrombotic syndrome in venous
thrombosis(1,2,4).
In our first case, prolonged rupture of membrane(more than
the probable risk factors for the development of portal vein thrombosis.
Similarly in the second case, emergency c-section, meconium stained
liquor, birth asphyxia and umbilical vein and artery catheterization
were the likely factors for thrombus development.
Clinical presentations of neonatal thrombosis are nonspecific and
depends on various factors, including the anatomic location of the
thrombosis, the presence of organ damage, the characteristics of the
thrombus (occlusive vs nonocclusive), the chronicity of the thrombosis,
and the underlying clinical status of the
patient(2). Although
diagnosis is an incidental finding during imaging, most of the neonates
might have some symptoms at the time of diagnosis. In the first case,
the neonate had persistent vomiting and in the second case, there were
pale and cold peripheries and absent femoral pulses bilaterally.
Different imaging modalities such as doppler ultrasound,
echocardiography, venography/angiography, CT or MRI can be used to make
a diagnosis of thrombosis, and choice of imaging modalities depends upon
the location of the thrombus. Incidental portal vein thrombosis was
found during abdominal ultrasound in our first case reports. However,
diagnostic doppler ultrasound was considered in the second case after
the neonate had symptoms of arterial obstruction.
Several factors such as location of the thrombus, extension of thrombus,
clinical status of the patients are very important to consider while
managing neonatal thrombosis. Proper guidelines for the management of
thrombosis in neonates are lacking, therefore management of such
conditions requires experts’ opinions, individualization of each case
and guidance from studies done in the adult
population(14)].
The primary goal of management using anticoagulants is to prevent short
term such as extension of thrombus, organ damage, thrombus embolization,
limb loss and long term complications recurrence of thrombus, portal
hypertension and gastrointestinal bleeding in case of
PVT(15–17).
Unfractionated heparin, low molecular weight heparin, vitamin k
antagonist, direct thrombin inhibitor(intravenous or oral) and
thrombolysis are the choices for the management, however low molecular
weight heparin remains the drug of choice for the pediatric
population(2). In
both cases, we used enoxaparin(LMWH) at the recommended dose of 1.5
mg/kg/dose twice
daily(18). Regular
completed blood count was performed to rule out heparin induced
thrombocytopenia, however due to resource limited setting and financial
issues of families we were not able to check anti-Xa level for
monitoring(2,19).