Cerebral Venous Sinus Thrombosis in a Pediatric Patient With COVID-19

Case

A 13-year-old female child, with a persistent oval foramen successfully treated at the first year of life and no other known comorbidities, presented to the emergency department with impaired consciousness and intense headache (visual analog scale of 8). Her parents reported symptoms beginning a week before: fever, cough, and odynophagia, followed by frontal headache and vomiting.

On physical examination, the patient was hemodynamically stable, with a Glasgow Come Scale score of 14, bradypsychia, and no focal neurologic deficit or meningeal signs. Urgent head CT scan revealed right occipital intracerebral hemorrhage, and magnetic resonance angiogram showed bilateral transverse sinus thrombosis with extension to the right sigmoid sinus and internal jugular vein (figure, A and B). A thorax x-ray showed right basal opacity. Initial laboratory tests reported inflammatory markers as mild leukocytosis (14,460 per mm³) with lymphopenia (1,800 per mm³), increase of lactate dehydrogenase 322 U/L (100–250), serum ferritin 240 ng/mL (7–140), C-reactive protein of 12.55 mg/dL, and abnormal coagulation parameters compatible with overt-disseminated intravascular coagulation³ such as platelet count of 55,000 per mm³, prothrombin index of 43% (75–110), fibrinogen of 0 mg/dL, and D-dimer of 33.96 mg/L (0–0.5).

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Figure Cerebral Sinus Venous Thrombosis and Cerebral Venous Infarction

(A) Right occipital intracerebral hemorrhage is seen on initial head CT scan. (B) Anteroposterior view of initial 3D MRA shows venous flow occlusion at the final part of superior sagittal sinus (blue arrow) due to bilateral transverse sinus thrombosis extending to the right jugular vein. Left sigmoid sinus is filled by the vein of Labbé (white arrow). (C) Head contrast CT scan on follow-up demonstrates repletion defect in the posterior half of superior sagittal sinus (white star). MRA = MR angiogram.

The patient was admitted to the pediatric intensive care unit. Intravenous hydration, empiric antibiotics, and intracranial hypertension medical treatment were started, requiring hypertonic saline bolus for bradycardia episodes (35 bpm). Fibrinogen and platelet and plasma transfusion were administered. PCR for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by oropharyngeal swab was positive confirming COVID-19, thus lopinavir-ritonavir, hydroxychloroquine, and azithromycin were also initiated.

Unfractionated heparin anticoagulation was started at an initial infusion rate of 10 U/kg/h, adjusted to maintain partial thromboplastin time ratio of 1.5–2.5, prompted by bilateral sinus thrombosis, intracranial hypertension symptoms and sings, and the high mortality rate associated,⁴ despite the risk of worsening cerebral hemorrhage.

Over the subsequent 72 hours, there was progressive clinical improvement. However, on the fifth day of admission, body angio-CT scan revealed thrombosis progression toward the posterior half of the superior sagittal sinus (figure, C), as well as bilateral pulmonary thromboembolism and bilateral deep femoral and iliac veins thrombosis reaching infrarenal cava, associating left leg edema as the sole clinical sign and no hemodynamic changes. Thus, anticoagulation doses were increased at 20 U/kg/h.

Regarding multiple vein thrombosis, the patient did not have a family history of autoimmune disease or genetic prothrombotic condition. Mycoplasma, parvovirus, Toxoplasma gondii, cytomegalovirus, Epstein-Barr, Varicella zoster, Herpes simplex 1 and 2, hepatitis B and C viruses, and HIV were ruled out. The autoimmune panel for lupus and antiphospholipid syndrome only showed a weak positive for lupus anticoagulant. However, at a 2-week follow-up a slight increase of aCL IgG 23 U/mL (0–20) was also noted. Both parameters were normalized 1 month later. In addition, protein C and S, homocysteine, antithrombin III, and anti Xa were also normal. Mutation for factor V Leiden and prothrombin 20210 were negative.

Despite the severe coagulopathy developed by our patient with COVID-19, the known associated poor prognosis,⁴ and the severity of the cerebral venous sinus thrombosis, the child was discharged with good clinical outcome, asymptomatic and without neurologic sequelae after 24 days of admission.