Postoperative Pharmacologic Anticoagulation following Temporal Postoperative Pharmacologic Anticoagulation following Temporal Lobe Resection of a Gliosarcoma in a Hypercoagulable Patient Lobe Resection of a Gliosarcoma in a Hypercoagulable Patient

Gliosarcomas are a rare subtype of glioblastomas associated with high rates of malignancy-associated venous thromboembolism (VTE). VTE risk is further increased in hypercoagulable patients upon discontinuing pharmacologic anticoagulation for surgery. We present a 60-year old obese male with history of hypercoagulability on apixaban who developed extensive thrombosis following resection of a gliosarcoma. Prior to temporal lobe resection, apixaban was discontinued and an IVC filter placed. On postoperative day 4, imaging revealed thrombosis above the IVC filter extending to the bilateral common, internal and external iliac, and femoral veins, requiring immediate anticoagulation and suction thrombectomy. Clinicians must balance the risk of VTE and intracerebral hemorrhage following neurosurgical procedures. While withholding pharmacologic VTE is standard, hypercoagulable patients may benefit from earlier institution of pharmacologic prophylaxis postoperatively. Patients with multiple risk factors including malignancies with high rates VTE, like gliosarcomas with medical and hematological conditions that predispose to clotting, including idiopathic erythrocytosis and history of VTE may benefit from earlier pharmacologic prophylaxis.


Postoperative Pharmacologic Anticoagulation following Temporal Lobe Postoperative Pharmacologic Anticoagulation following Temporal Lobe Resection of a Gliosarcoma in a Hypercoagulable Patient Resection of a Gliosarcoma in a Hypercoagulable Patient
This case reports and case series is available in Cooper Rowan Medical Journal: https://rdw.rowan.edu/crjcsm/vol3/ iss1/2

INTRODUCTION
Glioblastomas are the most common primary malignant brain tumors in adults with a median age of diagnosis around 55-60 years old. A rare histopathologic subtype of glioblastomas are gliosarcomas, an isocitrate dehydrogenase wild type glioblastoma, comprising approximately 2-3% of all WHO Grade IV primary glioblastomas. 1,2 All glioblastomas are derived from astrocytes, the most common type of glial cell. Glioblastomas are a heterogenous group of malignant tumors without a common genetic signature and varied histopathology, location, and genetic mutations. 3 The gliosarcoma variation of glioblastomas can occur sporadically as a primary malignancy, or be a secondary malignancy following radiation to the brain. 4 Gliosarcomas display biphasic histopathology, containing gliomatous differentiation, present in all glioblastomas, as well as mesenchymal components, classically associated with sarcomas, and high grade malignant cells with areas of necrosis, mitosis and atypia. 5 These mesenchymal components resemble histopathology associated with liposarcoma, chondrosarcoma, and osteosarcomas. 6,7 Clinically, gliosarcomas have been traditionally viewed similarly to other grade IV glioblastomas, sharing similar rates of survival, response to treatments, and rates of recurrence. [8][9][10] A challenging aspect of management shared by glioblastomas and gliosarcomas is the risk of venous thromboembolism (VTE), especially after neurosurgical intervention. Malignancies dramatically increase the risk of VTE by more than five-fold, with 30% of all VTE occurring in the setting of malignancy. 11,12 The rate of VTE in high grade gliomas is 20-30%, and as high as 25-39% in patients with high grade glioblastoma. 11,13 Pharmacologic prophylaxis and intervention for postoperative VTE is complicated following intracranial surgery. The risk of VTE must be weighed against the risk anticoagulation leading to intracerebral hemorrhage (ICH), which occurs in nearly 2% of patients following intracranial tumor resection. 14 We present a case of a patient with a history of hypercoagulability and deep vein thrombosis (DVT) in the setting of idiopathic erythrocytosis on chronic anticoagulation who developed extensive VTE after resection of a grade IV gliosarcoma.

Case Report
A 60-year-old obese male with a history of hypertension, diabetes mellitus, idiopathic erythrocytosis requiring intermittent phlebotomy and DVT in the setting of erythrocytosis, currently on apixaban presented to the emergency department with a two-week history of unilateral, pulsating, temporal headaches, which progressed to 10/10 pain on the day of admission. Associated symptoms include nausea, blurry vision, and difficulty with ambulation. Of note, the idiopathic erythrocytosis work up eight years ago for genetic and paraneoplastic etiologies was inconclusive; negative for JAK2, MPL, and calreticulin mutations and no renal or liver masses were present. Three years ago, the patient developed a lower extremity DVT secondary to erythrocytosis, underwent a thrombectomy and has been on apixaban for future DVT prophylaxis.
On physical exam, no focal neurological deficits were appreciated, however the fundoscopic exam The patient was discharged on postoperative day 11 on therapeutic LMWH. LMWH was chosen in place of a direct oral anticoagulation due to the risk of future neurosurgical intervention and availability of a reversal agent. He is continuing his care with neurosurgery and radiation oncology, feeling well and has not developed any further VTE since discharge.

DISCUSSION
Gliosarcomas are a rare subtype of glioblastomas occurring in a similar patient demographic, with unique histopathological features, and a grim prognosis. 9,10 The histological and radiographic findings seen in our patient are consistent with the classical appearance of gliosarcoma as reported in literature. 14,15 The temporal lobe is the most common location, commonly seen with surrounding vasogenic edema on imaging as seen in our patient. 4 Immunohistological stains showed glial component that was rich in glial fibrillary acidic protein (GFAP). The mesenchymal components showed spindle cell sarcoma rich in reticulin and poor in GFAP. P53 is about 23% mutated in gliosarcoma and in our patient p53 was not mutated. 15 The development of VTE is a common complication in patients with any malignancy, but particularly high grade glioblastomas and gliosarcomas. 12,13 The postoperative complications that occurred in our patient highlights the difficult management decisions that must be made while caring for these patients. Chemical

VTE prophylaxis is challenging in high grade gliomas resections as current American Society of Clinical
Oncology guidelines recommend pre-and post-surgery chemical VTE prophylaxis in cancer patients. 16 However, preoperatively, chemical prophylaxis for neurosurgical procedures has been shown to increase the risk of intraoperative bleeding. 17 Therefore, postoperatively, mechanical prophylaxis alone is often preferred by neurosurgeons because of the reduced risk of developing ICH when compared to chemical prophylaxis. An alternative approach to prevention of VTE is the placement of an IVC filter. However, recent data has shown that chemical prophylaxis combined with mechanical prophylaxis is superior to IVC filters and does not increase the risk of ICH when administered 24 hours after surgery. 18 In addition, extensive thrombosis of the IVC filter can occur without chemical prophylaxis and removal of thrombi can potential put those patients at higher risk for adverse events. The risk of clot removal might outweigh the benefit of its placement. 19 Risk factors for thrombosis, in addition to the underlying malignancy, must be considered. Prolonged Multiple hypercoagulable risk factors work synergistically, increasing risk of VTE by several fold. As such, patients with multiple hypercoagulable risk factors may benefit from more aggressive prophylaxis following intracranial mass resection than patients without other hypercoagulable state inducing comorbidities.