Clinical and Laboratory Data
A magnetic resonance imaging (MRI) scan with contrast was performed on the patient. The results were initially reported as being unremarkable (Image 1).
Axial magnetic resonance imaging (MRI) scan of our patient, a 22-year-old obese Caucasian woman. The image shows sections at the levels of the lateral ventricles and the cerebellum/optic nerves. On initial review, the images were reported as being unremarkable. Further review demonstrated the presence of sagittal sinus hyperintensity (short red arrow) with swirling effect and bulging of the optic nerves bilaterally (long red arrows).
A spinal tap demonstrated an elevated opening pressure of 31 cm H2O, but the results were otherwise unremarkable (Table 1). Due to the evidence of intracranial hypertension on lumbar puncture, the clinical team sought a second opinion on the results of the MRI that had been performed earlier. Further review demonstrated the presence of sagittal sinus hyperintensity with a swirling effect and bulging of the optic nerves bilaterally, which was indicative of cerebral venous sinus thrombosis.
A computed tomography (CT) scan with contrast was ordered to evaluate the extent of thrombosis (Image 2). The CT scan revealed extensive left-sided subtotal dural venous sinus thrombosis, involving the superior sagittal sinus, straight sinus, and transverse sinus; partial empty sella; and buckling of the optic nerves bilaterally, all of which were suggestive of intracranial hypertension.
Computed tomography (CT) scan of our patient, a 22-year-old obese Caucasian woman. The contrast shows extensive left subtotal dural venous sinus thrombosis involving the superior sagittal sinus, straight sinus, and transverse sinus (red arrows).
A complete blood count revealed a microcytic, hypochromic anemia on admission, with a hemoglobin level of 6.3 g per dL; 2 units of packed red blood cells were transfused to correct the anemia. Further treatment included anticoagulation with warfarin, using a heparin bridge and intracranial thrombectomy due to the high clot burden. Four days later, bilateral optic nerve fenestration was performed to address the worsening visual acuity and a ventriculoperitoneal shunt was inserted for management of intracranial hypertension.
A coagulation work-up was conducted in parallel to these treatment measures, to investigate for the underlying cause of cerebral sinus thrombosis in the patient. The results of the initial investigations are shown in Table 2. The hypercoagulable work-up results were negative for lupus anticoagulant, anticardiolipin antibodies, and beta-2 glycoprotein-I antibodies on 2 separate occasions in September 2014 and early October 2014. On initial testing, the patient was noted to have elevated Factor VIII:C activity with a peak level of 5.54 U per mL; however, repeat testing in the steady state demonstrated normal levels (1.47 U per mL). The low activated partial thromboplastin time (APTT) results were likely secondary to the elevated Factor VIII:C as part of the acute-phase response. Protein C activity was mildly decreased at 64%; however, repeat testing while the patient had temporarily stopped taking warfarin demonstrated normal protein C activity (96%). The rest of the hypercoagulable work-up results were unremarkable. Flow cytometric tests performed for glycosylphosphatidylinositol (GPI)–linked antigens and fluorescent aerolysin (FLAER) on peripheral blood cells to rule out paroxysmal nocturnal hemoglobinuria (due to the combination of anemia and thrombosis) yielded negative results.
Due to the age of the patient and her extensive clot burden, we performed further tests to investigate for an underlying defect in fibrinolysis. Repeat testing revealed a persistently elevated plasminogen activator inhibitor (PAI)–1 activity level with a corresponding elevation in PAI-1 antigen concentration (Table 3). The patient was also found to be homozygous for the PAI-1 4G/4G polymorphism. In addition, Janus kinase 2 (JAK2) mutation test results were negative, and repeat protein C activity levels were within the normal range.
Lab Med. 2016;47(3):223-240. © 2016 American Society for Clinical Pathology