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).