CLINICAL REPORT
Rapid Anticoagulation Reversal With Prothrombin Complex Concentrate Before Emergency Brain Tumor Surgery Christopher Beynon, MD, Anna Potzy, MD, Christine Jungk, MD, Andreas W. Unterberg, MD, PhD, and Oliver W. Sakowitz, MD, PhD
Background: Brain tumors may become symptomatic due to intracranial hypertension and patients may present to emergency departments in life-threatening conditions. Hence, emergency brain tumor surgery has to be considered, but sufficient hemostasis has to be present when initiating surgical procedures. Impaired hemostasis because of oral anticoagulation for the treatment of cardiovascular diseases is encountered in a growing number of patients. Here we present the first case series of anticoagulated patients receiving prothrombin complex concentrate (PCC) to rapidly restore hemostasis and facilitate emergency brain tumor surgery. Methods: We retrospectively analyzed our institutional database of neurosurgical patients receiving PCC from February 2007 to April 2013 (n = 432) and identified 5 patients who received PCC before emergency brain tumor surgery. Clinical characteristics, as well as modalities of PCC administration and parameters of hemostasis were analyzed. Results: Patients had a mean Glasgow Coma Scale score of 9.4 at admission. Mean international normalized ratio was 3.75 ± 1.98 and after administration of PCC (mean, 3260 ± 942 IU), international normalized ratio significantly decreased to 1.19 ± 0.07 (P < 0.0001). Emergency brain tumor surgery was initiated within 5.2 hours (range, 0 to 13.5 h) after PCC administration. Diagnostic histopathology revealed metastasis (n = 2), meningioma (n = 2), and ependymoma (n = 1). No hemorrhagic or thromboembolic events occurred and 4 patients had a good neurological outcome at hospital discharge. One patient died on the 14th postoperative day because of respiratory failure following development of pneumonia. Conclusions: In anticoagulated patients with brain tumors requiring immediate surgery due to life-threatening conditions, administration of PCC rapidly and safely restored hemostasis. PCC administration seems to be an effective option for anticoagulant Received for publication April 25, 2014; accepted July 8, 2014. From the Department of Neurosurgery, Heidelberg University Hospital, Heidelberg, Germany. C.B. and O.W.S. have received speaker honoraria from CSL Behring. The other authors have no funding or conflicts of interest to disclose. Reprints: Christopher Beynon, MD, Department of Neurosurgery, Heidelberg University Hospital, Im Neuenheimer Feld 400, Heidelberg 69120, Germany (e-mail: christopher.beynon@med. uni-heidelberg.de). Copyright r 2014 Wolters Kluwer Health, Inc. All rights reserved.
246 | www.jnsa.com
reversal in this patient cohort. Further observational safety studies (eg, thromboembolic events) are warranted. Key Words: phenprocoumon, warfarin, anticoagulation reversal, hemostasis, brain tumor, intracranial neoplasm (J Neurosurg Anesthesiol 2015;27:246–251)
P
atients with brain tumors may present emergently with acute neurological deterioration or even comatose due to elevated intracranial pressure. As increased intracranial pressure especially occurs with large tumor size, extensive perifocal edema, or intratumoral hemorrhage, immediate brain tumor surgery has to be considered to avoid neurological sequelae or a fatal outcome. Because of the high incidence of cardiovascular diseases in industrialized countries, emergency physicians are increasingly confronted with patients treated with oral anticoagulants. Administration of prothrombin complex concentrate (PCC), a combination of the vitamin K-dependent clotting factors (II, VII, IX, and X), is an effective option to improve hemostasis. European Guidelines recommend the use of PCC not only for the management of bleeding complications, but also for the urgent reversal of anticoagulation in life-threatening hemorrhage.1 To the best of our knowledge, administration of PCC to facilitate emergency brain tumor surgery has not been reported before. Here we report our experiences in 5 anticoagulated patients who were admitted to our hospital in critical conditions and treated by emergency brain tumor surgery after administration of PCC had restored hemostasis. Patient characteristics regarding clinical presentation, laboratory values, and surgical treatment are analyzed. Furthermore, modalities of PCC administration are studied and the outcomes of patients are analyzed with specific focus on hemorrhagic and thromboembolic complications.
MATERIALS AND METHODS For this study, our institutional database of all neurosurgical patients who received PCC was retrospectively analyzed (n = 432). Data from all anticoagulated patients who received PCC before emergency brain tumor surgery from February 2007 to April 2013 J Neurosurg Anesthesiol
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Volume 27, Number 3, July 2015
J Neurosurg Anesthesiol
Volume 27, Number 3, July 2015
were included (n = 5). Data were obtained retrospectively by chart review. The decisions to perform emergency surgery and to reverse anticoagulant effects through administration of PCC were based on the patient’s clinical condition and were taken by the consultant neurosurgeon in charge. For anticoagulant reversal, PCC (Beriplex P/N 500; CSL Behring GmbH, Marburg, Germany) was administered intravenously. To establish sufficient hemostasis, PCC dosage was calculated to achieve international normalized ratio (INR) levels of r1.3 according to manufacturer’s instructions (dosage, 25 to 50 IU/kg body weight). Surgery was initiated when hemostasis was restored and preparations for surgery were completed. Blood was drawn after PCC administration for INR assessment at the central laboratory. As a postoperative standard procedure in orally anticoagulated patients, vitamin K was given to avoid postoperative oral anticoagulant-associated rebound increase of INR. All patients received low–molecular-weight heparin (Clexane; Sanofi, Frankfurt, Germany) in addition to compression stockings. During the further in-hospital course, diagnostic procedures regarding thromboembolic or hemorrhagic events were carried out if corresponding clinical symptoms occurred. For statistical comparison of INR values before and after PCC administration, we used the paired 1-sided Student t test (GraphPad Prism 5, GraphPad Software).
RESULTS Patient Characteristics and Modalities of PCC Administration PCC was administered in 5 patients with impaired hemostasis due to oral anticoagulation and acute neurological deterioration requiring emergency brain tumor surgery (Fig. 1). In all patients intracranial neoplasms were previously undiagnosed. Characteristics of patients regarding their acute pathology as well as laboratory values obtained before and after PCC administration are summarized in Table 1. All patients had received phenprocoumon because of atrial fibrillation and had a Glasgow Coma Scale score
Rapid Anticoagulation Reversal With Prothrombin Complex Concentrate Before Emergency Brain Tumor Surgery Christopher Beynon, MD, Anna Potzy, MD, Christine Jungk, MD, Andreas W. Unterberg, MD, PhD, and Oliver W. Sakowitz, MD, PhD
Background: Brain tumors may become symptomatic due to intracranial hypertension and patients may present to emergency departments in life-threatening conditions. Hence, emergency brain tumor surgery has to be considered, but sufficient hemostasis has to be present when initiating surgical procedures. Impaired hemostasis because of oral anticoagulation for the treatment of cardiovascular diseases is encountered in a growing number of patients. Here we present the first case series of anticoagulated patients receiving prothrombin complex concentrate (PCC) to rapidly restore hemostasis and facilitate emergency brain tumor surgery. Methods: We retrospectively analyzed our institutional database of neurosurgical patients receiving PCC from February 2007 to April 2013 (n = 432) and identified 5 patients who received PCC before emergency brain tumor surgery. Clinical characteristics, as well as modalities of PCC administration and parameters of hemostasis were analyzed. Results: Patients had a mean Glasgow Coma Scale score of 9.4 at admission. Mean international normalized ratio was 3.75 ± 1.98 and after administration of PCC (mean, 3260 ± 942 IU), international normalized ratio significantly decreased to 1.19 ± 0.07 (P < 0.0001). Emergency brain tumor surgery was initiated within 5.2 hours (range, 0 to 13.5 h) after PCC administration. Diagnostic histopathology revealed metastasis (n = 2), meningioma (n = 2), and ependymoma (n = 1). No hemorrhagic or thromboembolic events occurred and 4 patients had a good neurological outcome at hospital discharge. One patient died on the 14th postoperative day because of respiratory failure following development of pneumonia. Conclusions: In anticoagulated patients with brain tumors requiring immediate surgery due to life-threatening conditions, administration of PCC rapidly and safely restored hemostasis. PCC administration seems to be an effective option for anticoagulant Received for publication April 25, 2014; accepted July 8, 2014. From the Department of Neurosurgery, Heidelberg University Hospital, Heidelberg, Germany. C.B. and O.W.S. have received speaker honoraria from CSL Behring. The other authors have no funding or conflicts of interest to disclose. Reprints: Christopher Beynon, MD, Department of Neurosurgery, Heidelberg University Hospital, Im Neuenheimer Feld 400, Heidelberg 69120, Germany (e-mail: christopher.beynon@med. uni-heidelberg.de). Copyright r 2014 Wolters Kluwer Health, Inc. All rights reserved.
246 | www.jnsa.com
reversal in this patient cohort. Further observational safety studies (eg, thromboembolic events) are warranted. Key Words: phenprocoumon, warfarin, anticoagulation reversal, hemostasis, brain tumor, intracranial neoplasm (J Neurosurg Anesthesiol 2015;27:246–251)
P
atients with brain tumors may present emergently with acute neurological deterioration or even comatose due to elevated intracranial pressure. As increased intracranial pressure especially occurs with large tumor size, extensive perifocal edema, or intratumoral hemorrhage, immediate brain tumor surgery has to be considered to avoid neurological sequelae or a fatal outcome. Because of the high incidence of cardiovascular diseases in industrialized countries, emergency physicians are increasingly confronted with patients treated with oral anticoagulants. Administration of prothrombin complex concentrate (PCC), a combination of the vitamin K-dependent clotting factors (II, VII, IX, and X), is an effective option to improve hemostasis. European Guidelines recommend the use of PCC not only for the management of bleeding complications, but also for the urgent reversal of anticoagulation in life-threatening hemorrhage.1 To the best of our knowledge, administration of PCC to facilitate emergency brain tumor surgery has not been reported before. Here we report our experiences in 5 anticoagulated patients who were admitted to our hospital in critical conditions and treated by emergency brain tumor surgery after administration of PCC had restored hemostasis. Patient characteristics regarding clinical presentation, laboratory values, and surgical treatment are analyzed. Furthermore, modalities of PCC administration are studied and the outcomes of patients are analyzed with specific focus on hemorrhagic and thromboembolic complications.
MATERIALS AND METHODS For this study, our institutional database of all neurosurgical patients who received PCC was retrospectively analyzed (n = 432). Data from all anticoagulated patients who received PCC before emergency brain tumor surgery from February 2007 to April 2013 J Neurosurg Anesthesiol
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Volume 27, Number 3, July 2015
J Neurosurg Anesthesiol
Volume 27, Number 3, July 2015
were included (n = 5). Data were obtained retrospectively by chart review. The decisions to perform emergency surgery and to reverse anticoagulant effects through administration of PCC were based on the patient’s clinical condition and were taken by the consultant neurosurgeon in charge. For anticoagulant reversal, PCC (Beriplex P/N 500; CSL Behring GmbH, Marburg, Germany) was administered intravenously. To establish sufficient hemostasis, PCC dosage was calculated to achieve international normalized ratio (INR) levels of r1.3 according to manufacturer’s instructions (dosage, 25 to 50 IU/kg body weight). Surgery was initiated when hemostasis was restored and preparations for surgery were completed. Blood was drawn after PCC administration for INR assessment at the central laboratory. As a postoperative standard procedure in orally anticoagulated patients, vitamin K was given to avoid postoperative oral anticoagulant-associated rebound increase of INR. All patients received low–molecular-weight heparin (Clexane; Sanofi, Frankfurt, Germany) in addition to compression stockings. During the further in-hospital course, diagnostic procedures regarding thromboembolic or hemorrhagic events were carried out if corresponding clinical symptoms occurred. For statistical comparison of INR values before and after PCC administration, we used the paired 1-sided Student t test (GraphPad Prism 5, GraphPad Software).
RESULTS Patient Characteristics and Modalities of PCC Administration PCC was administered in 5 patients with impaired hemostasis due to oral anticoagulation and acute neurological deterioration requiring emergency brain tumor surgery (Fig. 1). In all patients intracranial neoplasms were previously undiagnosed. Characteristics of patients regarding their acute pathology as well as laboratory values obtained before and after PCC administration are summarized in Table 1. All patients had received phenprocoumon because of atrial fibrillation and had a Glasgow Coma Scale score
