Background: MTHFR polymorphism has been inconsistently linked to thrombotic events—some studies have shown its contribution to venous thrombosis, arterial thrombosis, and ischemic stroke, whereas others have found no statistically significant correlation between them. Methods: A descriptive case series study was performed in the Neonatal Intensive Care Unit of “Marie Sklodowska Curie” Emergency Clinical Hospital for Children in Bucharest, Romania. Results: All patients had positive results for MTHFR variants; 14 patients were positive for compound heterozygosity, 13 patients for MTHFR C677T (seven of which were homozygous), and 13 patients for MTHFR A1298C (three of which were homozygous). Eighteen patients received anticoagulants (heparin, enoxaparin, or bivalirudin), and thrombolytics (alteplase) were administered in six cases. In one case, a thrombectomy was performed; in another, vascular plasty was undertaken. Only in six cases was complete revascularization possible. Incomplete revascularization occurred for one patient with a negative outcome. Conclusion: The particularity of this case series is that every patient in our unit who developed thrombi had a positive genetic result for MTHFR mutations. MTHFR mutations should be regarded as a thrombotic risk factor for critically ill patients, and screening for MTHFR mutations should be performed in every admitted patient to intensive care units, thus achieving the prevention of thrombi.
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