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Purpose: To describe the demographics, clinical presentation, treatment, and outcomes of a rare cohort with simultaneous orbital and intracranial abscesses. Methods: A historical cohort study of 17 patients with simultaneous orbital and intracranial abscesses between 2010 and 2018 was performed. The demographics, location of abscesses, treatment, and outcomes of these patients were analyzed. Results: The mean age was 26.9 years (range 5–83 years). Fourteen patients (82%) were male. In this cohort, the most common orbital abscess location was the superior orbit, involved in 14 patients (82%). The most common site of intracranial abscess was the frontal lobe, involved in 16 patients (94%). Concurrent sinus disease was present in 16 patients (94%). Surgical evacuation was the standard of treatment, with 94% of patients undergoing at least one surgical procedure. Streptococcus species were the most common, isolated from 6 sinus cultures (43%), 3 orbitotomy cultures (21%), and 4 craniectomy cultures (36%). Staphylococcus species were also common. Most patients (94%) had stable or improved mental status and visual function at the conclusion of their treatment. Conclusions: Simultaneous orbital and intracranial abscesses are rare. Local invasion from the orbit into the intracranial space may occur from direct spread, thus superior orbital abscesses pose the greatest risk for intracranial spread. Additional factors such as infection with Streptococcus and Staphylococcus species as well as male sex appear to be risk factors for intracranial spread. For those who develop intracranial abscesses, young age and absence of seizures or altered mental status at presentation may be associated with favorable outcomes.

Vepoloxamer alone modestly increased bleeding time. Vepoloxamer also increased bleeding time in rats treated with low-dose heparin but not with high-dose heparin. Vepoloxamer potentiated clot lysis in the setting of low-dose tPA.

Introduction: MST-188 (purified poloxamer 188) is a tri-block co-polymer with high affinity to hydrophobic cellular surfaces that inhibits hydrophobic adhesive interactions in the circulation. It also facilitates blood flow by reducing blood viscosity and reportedly exhibits anti-adhesion and anti-inflammatory properties. Currently, this agent is under study in with patients experiencingsickle cell crisis and in patients with acute limb ischemia. Since MST-188 may be administered with other anti-coagulant agents such as heparin its potential interaction to modulate the anti-coagulant effects of this drug require experimental validation. These studies are designed to investigate the potential interactions between heparin and MST-188 in a rat model of tail transection bleeding and jugular vein clamping induced thrombosis model. Materials and Methods: The in vitro interactions between MST-188 were investigated by supplementing this agent to normal rat plasma (NRP) and heparinized rat plasma at a fixed concentrations of 1.25 and 2.50 mg/mL. The concentration of heparin was kept at 1.25 and 2.50 μg/mL. In the in vivo studies individual groups of rats (n=6-8) were administered with saline as a control, heparin in the dosage range of 125-500 ug/kg intravenously and MST-188 at 25 mg/kg IV followed by heparin at the 125-500 ug/kg dosages. Rat tail resection time was measured 5 minutes after administration of heparin and clot occlusion index was measured as number of jugular vein clamping required to occlude the blood vessel. After the completion of the procedure blood samples were obtained through cardiac puncture and used for ex vivo analysis of PT, aPTT, heptest and thrombin time. Results: In the in vitro studies heparin produced a concentration dependent prolongation of the aPTT, heptest and thrombin time. MST-188 did not produce any effects on the aPTT and heptest time, however it decreased the thrombin time. MST-188 at a higher concentration of 2.5 and 5.0 mg/ml produced a shorting of heparins anticoagulant responses, as measured by aPTT and thrombin time. Heparin produced a dose dependent increase in both the bleeding time (p<0.0001) and number of jugular vein clamps to occlude the blood vessel (p<0.0001). MST-188 at dosages of 25 mg/kg produced a significant increase on both bleeding time (p <0.05) and number of clampings required to occlude the blood vessel (p<0.0001). When MST-188 was administered simultaneously with heparin it augmented the bleeding time (p < 0.05) and increased the number of jugular vein clamps required to occlude the blood vessel (p < 0.05). The ex vivo analysis of blood samples collected from rats treated in different regimens did not exhibit any anti-coagulant effects as measured by PT, aPTT, heptest and thrombin time. Conclusion: These studies suggest a differential response of MST-188. While in vitro it exhibits a prohemostatic response as evident by shortening of thrombin time, in the in vivo setting it enhances the anticoagulant effects of heparin as evident by increased bleeding time and increased number of jugular vein clamps required to occlude the vessel. Thus, both of these mechanisms are involved in the mediation of the beneficial effects observed with this agent in vaso-occlusive and thrombotic processes. Disclosures Emanuele: Mast Therapeutics: Employment.

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