Case
At presentation, the patient was in no apparent distress and had normal vital signs, including normal blood pressure. On physical examination, she was alert and oriented, with unremarkable head, neck, fundoscopic, cardiac, pulmonary, skin, and neurological examinations. Laboratory results were only notable for a platelet count of 677 x 109/L. The remainder of the complete blood count, chemistry, and coagulation panels was all within normal limits. A noncontrast computed tomography (CT) of the brain was unremarkable. She was treated symptomatically with ketorolac, diphenhydramine, and metoclopramide, but received no relief.
Based on the patient’s history of ET and postpartum state, there was a high suspicion for cerebral venous thrombosis (CVT). Magnetic resonance imaging/magnetic resonance venography (MRI/MRV) of the brain was obtained, which revealed near-complete thrombosis of the vein of Galen and straight sinus (Figure). Neurology and hematology services were consulted emergently, and the patient was started on a heparin drip and admitted to the neurosurgical intensive care unit. Hydroxyurea was also given for cytoreduction, and platelets normalized to 305 x 109/L within 1 day of treatment. The patient’s neurological examination remained nonfocal, her headache gradually resolved, and she was discharged on hospital day 3 on oral anticoagulants.
Discussion
Essential Thrombocytosis
Essential thrombocytosis is a chronic myeloproliferative disorder characterized by clonal proliferation of the megakaryocyte cell line due to a defect in a pluripotent hematopoietic stem cell.1 The estimated annual incidence is 2.5 per 100,000 individuals.2 It affects patients of both genders, most commonly between ages 50 to 70 years.3
Up to 25% of patients with ET experience neurological complications, mainly occlusive strokes, chronic headache, and dizziness.4 Since pregnancy also increases thrombogenicity, and CVT occurs in 12 per 100,000 deliveries,5 it should be considered in any pregnant or postpartum patient with neurological symptoms.
Diagnosis of ET
Essential thrombocytosis is a diagnosis of exclusion, and no clinical or laboratory finding is diagnostic.1 Although patients with ET are at increased risk for bleeding, these events usually involve mucosal and cutaneous sites and are clinically insignificant. Thrombotic complications account for the majority of the morbidity and mortality associated with ET and can be both arterial and venous. In one case series, roughly 50% patients with ET experienced a thrombotic event within 9 years from diagnosis.6 Thrombotic complications are seen most commonly in patients younger than age 55 years at diagnosis. Common sites of thrombosis include the deep veins of the lower extremities, pulmonary vessels, hepatic vein, portal vein, digital microvasculature, and placenta.1
Despite the high rate of thrombotic complications in ET, there is little data on neurological complications and few reports of CVT in patients with ET.7-9 In one chart review of 70 patients with ET, researchers identified 18 patients who developed neurological complications,4 the most common of which was cerebrovascular accident/transient ischemic attack. Only one patient in the series had a CVT. The majority of patients with neurological events were female and no clinical or laboratory parameter predicted the risk of neurological event.
Thrombocytosis
Thrombocytosis is classified as either primary/essential or secondary/reactive. The majority of thrombocytosis is secondary/reactive and is caused by a variety of inflammatory conditions, such as infection and malignancy. Unlike ET, secondary thrombocytosis is not associated with any bleeding or thrombotic complications and does not require direct treatment.1
Treatment of ET
The decision to treat ET is based on clinical parameters and is usually reserved for patients at high-risk of thrombosis, including those with history of thrombosis or platelets >1,500 x 109/L.1 The first-line agent for treatment of essential thrombocytosis, hydroxyurea has been shown to decrease thrombotic episodes.10 Other cytoreductive agents include anagrilide and interferon-α, the use of which is considered safe in pregnancy.1
Cerebral Venous Thrombosis
Cerebral venous thrombosis is a rare but potentially fatal condition. Patients may present with headache (95%), seizures (47%), and vision changes (41%), and may or may not have focal or generalized neurological deficits.11 Thrombosis can lead to venous obstruction, resulting in increased intracranial pressure and ultimately cerebral herniation and death. Predisposing risk factors for CVT include thrombophilic and procoagulant disorders, maxillofacial infections, trauma, malignancy, and vasculitides. Among female patients with CVT, studies show approximately 50% were on oral contraceptives and 20% were pregnant or in the postpartum period at the time of the event. Nearly half of patients with CVT have multiple risk factors.12
Diagnosis of CVT
Diagnosis of CVT requires a high clinical suspicion. Lumbar puncture usually reveals high opening pressure with normal cerebrospinal fluid analysis.13 The classic finding of CVT on a contrast-enhanced CT scan is the “empty delta sign,” which is a central hypointensity within the superior sagittal sinus secondary due to slow/absent flow surrounded by contrast enhancement in a triangular shape. An ischemic infarction crossing arterial boundaries or near a venous sinus—with or without a hemorrhagic component—is also suggestive of CVT. However, CT scans are read as normal or indeterminate in up to 30% patients.14 Moreover, while CT venography may visualize the cerebral venous system, there is a false-negative rate of 25%.15 Therefore, MRI with MRV is the gold standard for diagnosis.
Pregnancy and CVT
As previously noted, pregnant or postpartum patients are at an increased risk of developing CVT. During pregnancy, decreased levels of protein S inhibitors and increased levels of fibrinogen, clotting factors, and protein C inhibitors lead to increased thrombogenicity.16 Older maternal age, pregnancy-related hypertension, peripartum infections, and cesarean delivery also increase the risk of CVT.16
Patients with CVT associated with pregnancy have more acute onset of symptoms and neurological findings, and 2% to 10% less mortality than patients with CVT secondary to other etiologies. Cerebral venous thrombosis should be considered in the differential diagnosis of any pregnant or postpartum patient presenting with neurological symptoms.
Treatment of CVT
Regardless of underlying etiology or symptom duration, all patients with CVT should receive anticoagulation therapy. Unfractionated or low-molecular weight heparin has been shown to decrease thrombus propagation, increase the rate of recanalization, and improve long-term outcomes—even in the presence of intracranial hemorrhage.17 In the 30% to 40% of patients with CVT who present with intracranial hemorrhage, anticoagulation decreases mortality and is not associated with new or enlarged bleeding.17-19 Patients who continue to deteriorate despite anticoagulation therapy may benefit from endovascular thrombolysis or decompressive hemicraniectomy.20 In a study of patients with CVT, 80% had full recovery, 6% had minor disability, and 14% had a poor outcome.12