Neonatal Medullary Venous Thrombosis and Hemorrhage from Protein C Deficiency

A female neonate with a prenatal history of intrauterine growth restriction and liver calcifications was evaluated for bilateral corneal opacities. Infectious workup was negative. Head ultrasound showed cerebral white matter hyperechogenicity. Brain magnetic resonance imaging showed extensive medullary vein thromboses and associated cerebral white matter hemorrhagic infarcts ([Fig. 1]). The patient developed seizures and hydrocephalus. Whole exome sequencing revealed biallelic pathogenic variants in the PROC gene, consistent with severe, congenital protein C deficiency.[1]

Fig. 1 Brain MRI at 18 days shows extensive subacute hemorrhagic cerebral white matter necrosis with stellate margins manifesting mixed high/low signal on SWI (A), T1WI (B), DWI (C), and ADC (D); additional findings include germinal matrix hemorrhages (arrows, A), intraocular hemorrhage (arrow, B), and right temporal neuronal migrational abnormality (not shown). ADC, apparent diffusion coefficient; DWI, diffusion-weighted imaging; MRI, magnetic resonance imaging; SWI, susceptibility-weighted imaging; T1W1, T1-weighted imaging.

Protein C plays a critical role in coagulation homeostasis through inactivation of factors V and VIII, profibrinolytic activity, and modulating inflammation. Individuals with severe protein C deficiency may present with purpura fulminans, hemorrhagic skin necrosis, disseminated intravascular coagulation, and both arterial and venous thromboses.[1] [2] Ocular manifestations include leukocoria, microphthalmos, vascular occlusion, hemorrhage, and corneal opacities.[1] [2] [3] [4] In our patient, vascular thromboses likely caused hemorrhagic infarction and may have led to neuronal migration abnormalities. Liver calcifications may have resulted from in utero-hepatic ischemic events. Functional protein C assays are used for diagnosis with corroborative genetic testing. Treatment is with lifelong anticoagulation and protein C replacement with plasma or plasma-derived, viral-inactivated protein C concentrate. It is important to recognize the clinical aspects of this disease for timely diagnosis and treatment initiation to prevent further morbidity.[1]

Publication History

Received: 23 January 2023

Accepted: 20 February 2023

Accepted Manuscript online:
23 February 2023

Article published online:
22 March 2023

• References

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