Although relatively rare, thromboembolic events are a major complication of invasive procedures, mainly vascular catheterization, required for the survival of neonates admitted to the neonatal intensive care unit. Sometimes symptoms may be ambiguous and the diagnosis may not be immediate. The clinical relevance of polymorphism of methilene tetrahydrofolate reductase (MTHFR) gene heterozigosity and of omocystein level in the genesis of these thromboembolic events are poorly understood. We report two cases of thrombosis of the abdominal aorta, mimicking aortic coarctation, in two neonates, successfully treated at diagnosis with 170 UI/Kg of low molecular weight heparin (LMWH) twice daily, without side effects. Screening for prothrombotic defects revealed the heterozygosity for MTHFR C677T in both neonates and low omocystein level in one of them. We suggest that in newborns vascular thrombosis should be considered in the differential diagnosis of acute disorders of blood circulation at birth and familial thrombophilia should be investigated. LMWH therapy with a dose of 170 UI/Kg twice daily usually allows vascular recanalization, without side effects.
Two neonates were referred to our unit for suspected coarctation of the aorta. Angio computed tomography (CT) scan showed an extensive spontaneous thrombosis of the abdominal aorta. Both neonates were carrier of heterozygosity for methilene tetrahydrofolate reductase (MTHFR) C677T mutation.
A 32 weeks newborn boy was born, by cesarean section. Pregnancy was biamniotic dichorionic but was uneventful. At birth Apgar scores were 8 and 9 at 1 and 5 min, respectively; birth weight was 1472 g. An umbilical venous catheter was introduced. No arterial lines were placed. Because both femoral pulses were weak and pressure was not detectable in both legs, at 12 h of life the baby was transferred to our neonatal intensive care unit for a suspected coarctation of the aorta. Echocardiography excluded coarctation but Doppler ultrasound showed an important reduction of the flow in the abdominal tract of the aorta. A contrast CT scan revealed complete thrombosis of the abdominal aorta distal of the origin of the renal arteries, allowing no flow across the aorta and a collateral circulation already evident. The platelet count was 97 000/mm3, hematocrit was 48% and coagulation tests were within the normal range of values. Blood cultures were negative. Evaluation for congenital thrombophilia was performed: protein C was 24%, protein S was 33%, ATIII was 55%. Factor V Leiden and prothrombin G20210A mutations were absent. Polymorphism in the MTHFR gene was present as heterozygosis for C677T mutation. Homocysteine level was low (1.80 mmol/l; normal values 4 to 19 mmol/l).
We started low molecular weight heparin (LMWH) at a dose of 170 UI/kg twice a day subcutaneously, obtaining complete recanalization after 15 days of therapy (Figure 1). To date the baby is 2 years old and clinical conditions are good. An abdominal echography confirmed complete recanalization of the aorta and normal kidney measures. The baby is thriving well and does not suffer any intestinal malabsorption.
A 40 weeks newborn female was born by cesarean section. Pregnancy was uneventful. At birth Apgar scores were 8 and 9 at 1 and 5 min, respectively; birth weight was 2295 g. As there was the loss of lower extremity pulses and a difference in blood pressure between upper and lower limbs of more than 20 mm Hg, the baby was transferred to our neonatal intensive care unit at 6 days of life for a suspected coarctation of the aorta. No arterial lines were positioned. Echocardiography excluded the coarctation of the aorta. Doppler ultrasound of the abdominal aorta showed a thrombus starting below the emergence of the superior mesenteric artery to the right common iliac artery. The platelet count was 140 000/mm3, the hematocrit was 50% and the coagulation profile was within normal values. Blood cultures were negative. Evaluation for congenital thrombophilia showed protein C 26%, protein S 67%, ATIII 40%, factor V Leiden mutation and prothrombin G20210A mutations were absent. The baby was carrier of heterozygosis for C677T MTHFR mutation, and the homocysteine level was in the normal range of values (758 mmol/l, normal values 4 to 19 mmol/l).
Therapy with enoxaparine 170 UI subcutaneously twice a day was started. A contrast CT scan was performed 2 days after confirming the aortic thrombus. The angio CT repeated a month later showed recanalization of the aorta (Figure 2). To date the baby is 18 months old. An abdominal echography confirmed complete recanalization of the aorta and normal kidney measures. The baby is thriving well and does not suffer any intestinal malabsorption.
The incidence of symptomatic thrombosis is 5.1 per 100 000 live births1 and 2.4 per 1000 neonatal intensive care admissions.2 In the critically ill neonate the presence of indwelling catheters is the single greatest risk factor for arterial or venous thrombosis: prematurity, dehydration, sepsis, maternal diabetes and asphyxia are other risk factors.2 Spontaneous arterial thrombosis is a rare event,3, 4, 5 which should lead to the evaluation for congenital thrombophilia, as this can greatly enhance the risk of thromboembolic events.
Symptoms may be ambiguous and sometimes mimic other very different disorders, as coarctation of the aorta. Acute complications or arterial thrombosis can include renal hypertension, intestinal necrosis and peripheral gangrene, depending on the location.
Thrombosis occurs more frequently in the neonatal period than in any other period of childhood. An important risk factor appears to be inherited thrombophilia. The role of genetic factors, such as the factor V Leiden, antithrombin, protein C or protein S deficiency, the 20210A prothrombin mutation are recognized as common risk factors of thrombosis, whereas the MTHFR polymorphism, present in 10% of caucasian population, is associated with a low risk for thromboembolic events. Nonetheless increasing evidences suggest that the MTHFR 677TT genotype combined with other risk factors may contribute to thrombotic onset.6, 7
The treatment for neonatal thrombosis is still controversial, no guidelines currently exist, although suggested doses have been published for anticoagulation and thrombolysis.8
Thrombectomy in our cases was excluded due to the small caliber of the vessels. Thrombolysis, although very tempting, was not performed because of the high risk of bleeding due to prematurity considering also the presence of an efficient collateral circulation in both cases without significant ischemia. We therefore favored a low risk anticoagulant therapy. We did not use unfractioned heparin because of its serious side effects. LMWH can be given subcutaneously and it has a more predictable pharmacokinetic, thus reducing the need for monitoring patients.9 To date the dose of LMWH that reaches the therapeutic levels in plasma in neonates is still under discussion.10, 11 We started in both our cases with LMWH at a dosage of 170 UI/kg in order to reach as soon as possible an anti-factor Xa level in the range of 0.5 to 1 U/ml, thereby hopefully reaching the antithrombotic effect of enoxaparin sooner. Once recanalization was obtained, LMWH was replaced with low dose aspirin for 3 months (10 mg/kg three times a week).
We recommend that in newborns vascular thrombosis be considered in the differential diagnosis of acute disorders of blood circulation.
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The authors declare no conflict of interest.
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Piersigilli, F., Auriti, C., Landolfo, F. et al. Spontaneous thrombosis of the abdominal aorta in two neonates. J Perinatol 34, 241–243 (2014). https://doi.org/10.1038/jp.2013.154
- abdominal aorta
- neonatal thrombosis
- low molecular weight heparin
- factor Xa level
- coarctation of the aorta
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