Neonatal Seizures as a First Sign of Inferior Vena Cava Thrombosis: Diagnostic and Therapeutic Challenges

Authors: Mariana Oliveira Pereira, Rita Lages Pereira, Clara Machado, Albina Silva

To the Editors,

Inferior vena cava (IVC) thrombosis in neonates, although rare, represents significant clinical challenges due to its high morbidity and mortality rates. The etiology of IVC thrombosis is often multifactorial, particularly in critically ill neonates. Central venous catheters are a major contributing factor, as they are frequently employed in neonatal intensive care units (NICUs) and can cause endothelial damage, leading to thrombus formation. Additionally, systemic infections such as sepsis and dehydration, which are common in neonates with immature immune systems, further elevate the risk of thrombosis. In some instances, a genetic predisposition to thrombosis may also be contributing factors including antithrombin III deficiency, protein C or S deficiency, and Factor V Leiden mutation.^1^,^2^

The clinical presentation of IVC thrombosis in neonates is often insidious. Many cases may be asymptomatic or present with nonspecific symptoms, such as unexplained swelling of the lower extremities or abdominal distension, which can delay timely recognition and diagnosis. Ultrasound with Doppler imaging is the preferred modality for identifying IVC thrombi; however, the subtlety of symptoms and the limitations in detecting small or early-stage thrombi necessitate heightened clinical vigilance paramount.^1^

Managing IVC thrombosis in this vulnerable population is particularly challenging. The primary goal is to prevent clot progression while minimizing the risk of hemorrhagic complications, which are heightened in neonates due to their immature hemostatic systems. Although anticoagulation therapy is effective in preventing thrombus extension, it carries significant risks in neonates, especially those with other comorbidities.^1^,^3^

A full-term male newborn, delivered via cesarean section due to suspected maternal chorioamnionitis and meconium-stained amniotic fluid, required brief oxygen support at birth (Apgar scores of 9, 9, and 10). Cord blood gas analysis showed no signs of metabolic acidosis. At 8 hours of life, he was admitted to the NICU due to seizures, intermittent groaning, and feeding difficulties. He experienced focal right-sided clonic seizures that were difficult to control, necessitating treatment with phenobarbital and levetiracetam. Upon physical examination, the newborn appeared well-developed, with a regular heart rate and palpable pulses, demonstrating good peripheral perfusion in all extremities. No swelling was observed. Neurologically, he exhibited no focal deficits but was lethargic with axial hypotonia. His eyes remained closed, and his sucking reflex was weak.

Amplitude-integrated electroencephalography (aEEG) did not reveal any evidence of electrical seizures. Blood analysis indicated an elevated C-reactive protein (peak value of 169.1 mg/L) but no hematological abnormalities, including thrombocytopenia. A lumbar puncture revealed pleocytosis (128 cells/µL), prompting the initiation of antibiotics at meningeal doses (ampicillin and gentamicin). Subsequently, both blood and cerebrospinal fluid cultures remained negative. Magnetic resonance imaging of the brain performed on day 6 revealed bilateral neonatal ischemic strokes, with multiple diffusion-restricted lesions in both hemispheres, predominantly in the left parietal and subcentral regions, as well as the left insula, right occipitomesial region, and right temporo-occipital convexity. To investigate potential thrombotic events, an echocardiogram, along with renal and abdominal ultrasounds, was conducted. The echocardiogram showed a patent foramen ovale with a left-to-right shunt, but no other abnormalities. On day 14, abdominal imaging revealed echogenic material extending from the cranial portion of the IVC to the junction of the mid and distal segments, indicating IVC thrombosis (Figure 1).

Anticoagulation therapy with low-molecular-weight heparin (1.5 mg/kg, twice daily) was initiated on day 15. The newborn remained hemodynamically stable, with no other complications, and demonstrated gradual clinical improvement, leading to his discharge on day 28 of life. At 4 months of age, an ultrasound confirmed complete recanalization of the IVC, and anticoagulation therapy was discontinued. There was no known family history of thrombophilia. A comprehensive thrombophilia screening was conducted for the patient and his parents, yielding negative results. This screening included tests for Factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase (MTHFR) gene mutations, as well as deficiencies in protein S, protein C, and antithrombin III. Additionally, levels of homocysteine, lupus anticoagulant, and anticardiolipin antibodies were evaluated. Histopathological examination of the placenta confirmed maternal chorioamnionitis.

At 6 months of age, the infant exhibited no neurological deficits and demonstrated normal neurodevelopment.

This case highlights the complexities of managing neonatal thrombosis, particularly due to its uncertain etiology. While coagulopathy associated with neonatal infection is the most plausible explanation, the exact mechanism remains unclear, underscoring the need for further research. The multifactorial nature of neonatal thrombosis suggests that additional factors, such as dehydration, maternal influences, and vascular injury, may also play significant roles. Understanding these underlying causes is critical for developing targeted preventive strategies and treatment protocols.^1^,^2^

Managing neonatal thrombosis requires individualized risk-benefit assessments, particularly when considering anticoagulation therapy. The absence of standardized protocols and evidence-based guidelines further complicates these decisions. Subcutaneous enoxaparin is increasingly utilized in both term and preterm neonates, demonstrating its critical role in preventing long-term complications, as illustrated in this case.^1^,^3^,^4^

Furthermore, the potential long-term implications of neonatal thrombosis necessitate ongoing follow-up and evaluation of neurodevelopmental outcomes. A study conducted by Demirel et al^4^ (2011) indicates that while many infants experience favorable outcomes with appropriate treatment, some may face lasting challenges related to their initial thrombotic events. A multidisciplinary approach involving neonatologists, radiologists, and hematologists is essential for optimizing care and ensuring the best possible outcomes for infants with thrombosis. By integrating insights from these studies into clinical practice, healthcare providers can develop effective protocols tailored to the unique needs of neonates, ultimately improving their prognosis.^4^