American Journal of Emergency Medicine 32 (2014) 690.e3–690.e4
Contents lists available at ScienceDirect
American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
Case Report
A life-threatening complication of warfarin therapy in ED: diffuse alveolar hemorrhage☆,☆☆ Abstract Warfarin have some serious adverse effects, and bleeding is one of the most serious and frequent of them. In this case report, we present the diffuse alveolar hemorrhage case as a rare and life-threatening complication of warfarin. Warfarin is a vitamin K antagonist anticoagulant drug and has potential adverse effects. Warfarin adverse effects consist of the most frequent emergency department visits among all drug-related visits, and bleeding was reported as high as 10% to 16% annually [1]. In this study, we present the diffuse alveolar hemorrhage case as a rare and life-threatening complication of warfarin. A 49-year-old man was admitted to emergency department with dyspnea and hemoptysis for 2 hours. Upon history examination, it was learned that he had chronic obstructive lung disease and mitral valve replacement. His regular therapy was warfarin 0.5 mg tablet, verapamil 120 mg tablet, and albuterol inhaler. His vital signs were as follows: blood pressure, 145/85 mm Hg; pulse rate, 128 beats/min (regular); temperature, 37.8°C, and oxygen saturation, arterial, 89%. The patient was tachypneic, and lung examination showed bilateral crackles. He denied any additional medication use and/or trauma. There were prosthetic valve sounds and thoracotomy scar, but pretibial edema was not present. Laboratory values revealed a hemoglobin value of 13 mg/dL and white blood cell count of 24.3 × 10 3/mm 3 with 78% neutrophils. The platelet count was 145,000/mm 3. His prothrombin time was 88 seconds; international normalized ratio (INR), 7; and activated partial thromboplastin time, 29.7 seconds. Arterial blood gas values, with room air, showed a pH of 7.28, PCO2 of 55 mm Hg, and PO2 of 61.3 mm Hg. A chest radiograph showed diffuse alveolar infiltrates (Fig. 1); it was confirmed with a chest computed tomographic scan (Fig. 2). The patient was diagnosed as having diffuse alveolar hemorrhage; supplemental oxygen, intravenous vitamin K, and fresh-frozen plasma (FFP) therapy was started in the emergency department. His respiratory failure did not progress, and intubation or mechanical ventilation was not required. The patient was discharged after hospitalization for 2 days in intensive care unit and for 7 days in cardiovascular surgery clinic.
☆ Prior publication: This article has not been published or submitted for publication elsewhere, in whole or in part, before submission to the American Journal of Emergency Medicine. ☆☆ Conflict of interest: We declared that we have no commercial, financial, and other relationships in any way related to the subject of this article all that might create any potential conflict of interest. 0735-6757/© 2014 Elsevier Inc. All rights reserved.
Warfarin is a coumarin derivative and acts by interfering with the cyclic interconversion of vitamin K and its 2.3 epoxide. Long-term oral warfarin therapy is indicated with some circumstances (eg, valve replacement, atrial fibrillation, etc), and patients are monitored with INR levels. Unfortunately, many factors such as diet, concurrent medication changes, poor compliance, or alcohol consumption may result in unexpected fluctuations in INR levels. The main complication of oral warfarin therapy is bleeding, especially from vital organs such as the brain or lung [2]. Diffuse alveolar hemorrhage usually presents with hemoptysis, anemia, hypoxemic respiratory failure, and infiltrates with an alveolar pattern on chest radiograph. Hemorrhage originates from the microvasculature instead of parenchyma or bronchial circulation. Most of the cases are secondary to pulmonary renal syndromes, connective tissue disorders, and drugs [3–5]. Although any epidemiologic study could not be found in the literature given the exact numbers of diffuse alveolar hemorrhage cases secondary to warfarin therapy, case reports or case series were reported rarely. Interestingly, cases without complication were treated successfully, and none of them died [6–10]. In a retrospective study, Oymak et al [11] reported on 11 patients with alveolar hemorrhage syndrome, and 7 of them died. In this study, only 1
Fig. 1. Chest radiograph of the patient showing diffuse alveolar infiltrates.
690.e4
E. Uysal et al. / American Journal of Emergency Medicine 32 (2014) 690.e3–690.e4
Süleyman Solak, MD Department of Emergency Medicine Bagcilar Training and Research Hospital Bağcılar Eğitim ve Araştırma Hastanesi, Bağcılar Istanbul, Turkey E-mail address: [email protected] Yahya Ayhan Acar, MD Department of Emergency Medicine Etimesgut Military Hospital, Etimesgut Asker Hastanesi Etimesgut, Ankara, Turkey E-mail address: [email protected] Mustafa Yalimol, MD Department of Emergency Medicine Bagcilar Training and Research Hospital Bağcılar Eğitim ve Araştırma Hastanesi Bağcılar, Istanbul, Turkey E-mail address: [email protected]
Fig. 2. Chest computed tomographic scan demonstrating bilateral alveolar infiltration.
patient died of warfarin overdose, but he had mitral valve stenosis and concomitant viral pneumonia with elevated sedimentation rate. Early recognition of pulmonary hemorrhage in anticoagulated patients is important because reversal of anticoagulation can be lifesaving [4]. For the rapid reversal of anticoagulation in case of serious bleeding, 10 mg of vitamin K1 should be given by slow intravenous infusion, supplemented with transfusion of fresh-frozen plasma [2]. Patients on long-term warfarin therapy have a potential risk for bleeding, and these complications can be seen in therapeutic ranges. Emergency physicians should consider bleeding in all anticoagulated patients and the importance of early recognition of pulmonary hemorrhage for the reversal of anticoagulation.
Emin Uysal, MD Department of Emergency Medicine Bagcilar Training and Research Hospital Bağcılar Eğitim ve Araştırma Hastanesi, Bağcılar Istanbul, Turkey E-mail address: [email protected] Erdem Çevik, MD Department of Emergency Medicine Van Military Hospital, Van Askeri Hastanesi Altıntepe, Van, Turkey E-mail address: [email protected]
http://dx.doi.org/10.1016/j.ajem.2013.12.022 References [1] Wysowski DK, Nourjah P, Swartz L. Bleeding complications with warfarin use: a prevalent adverse effect resulting in regulatory action. Arch Intern Med 2007;167 (13):1414–9. [2] Hirsh J, Fuster V, Ansell J, Halperin JL. American Heart Association/American College of Cardiology F. American Heart Association/American College of Cardiology Foundation guide to warfarin therapy. J Am Coll Cardiol 2003;41(9): 1633–52. [3] Albelda SM, Gefter WB, Epstein DM, Miller WT. Diffuse pulmonary hemorrhage: a review and classification. Radiology 1985;154(2):289–97. [4] Finley TN, Aronow A, Cosentino AM, Golde DW. Occult pulmonary hemorrhage in anticoagulated patients. Am J Respir Crit Care Med 1975;112(1):23–9. [5] Newsome BR, Morales JE. Diffuse alveolar hemorrhage. South Med J 2011;104(4): 269–74. [6] Barnett VT, Bergmann F, Humphrey H, Chediak J. Diffuse alveolar hemorrhage secondary to superwarfarin ingestion. Chest 1992;102(4):1301–2. [7] Itoh M, Oh-Ishi S, Nemoto K, Senba S, Adachi H, Kishi K, et al. A case of diffuse alveolar hemorrhage associated with tegafur plus uracil and warfarin therapy. Clinical medicine insights Case reports 2011;4:73–7. [8] Waness A, Aldabbagh T, Harakati M. Diffuse alveolar haemorrhage secondary to warfarin therapy for atrial fibrillation: a case report and literature review. BMJ case reports 2009 2009. [9] Erdogan D, Kocaman O, Oflaz H, Goren T. Alveolar hemorrhage associated with warfarin therapy: a case report and literature review. Int J Cardiovasc Imaging 2004;20(2):155–9. [10] Nural MS, Baydın A, Karataş AD, Elmalı M. Diffuse alveolar hemorrhage due to warfarin overdose. Toraks Dergisi 2006;7(1):68–71. [11] Oymak S, Tokgöz B, Akgün H, Gülmez İ, Erdoğan N, Demir R, et al. Alveolar hemorrhage syndromes; clinical, pathological, and imaging features: analysis of eleven patients. Toraks Dergisi 2002;3(1):52–8.
Contents lists available at ScienceDirect
American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
Case Report
A life-threatening complication of warfarin therapy in ED: diffuse alveolar hemorrhage☆,☆☆ Abstract Warfarin have some serious adverse effects, and bleeding is one of the most serious and frequent of them. In this case report, we present the diffuse alveolar hemorrhage case as a rare and life-threatening complication of warfarin. Warfarin is a vitamin K antagonist anticoagulant drug and has potential adverse effects. Warfarin adverse effects consist of the most frequent emergency department visits among all drug-related visits, and bleeding was reported as high as 10% to 16% annually [1]. In this study, we present the diffuse alveolar hemorrhage case as a rare and life-threatening complication of warfarin. A 49-year-old man was admitted to emergency department with dyspnea and hemoptysis for 2 hours. Upon history examination, it was learned that he had chronic obstructive lung disease and mitral valve replacement. His regular therapy was warfarin 0.5 mg tablet, verapamil 120 mg tablet, and albuterol inhaler. His vital signs were as follows: blood pressure, 145/85 mm Hg; pulse rate, 128 beats/min (regular); temperature, 37.8°C, and oxygen saturation, arterial, 89%. The patient was tachypneic, and lung examination showed bilateral crackles. He denied any additional medication use and/or trauma. There were prosthetic valve sounds and thoracotomy scar, but pretibial edema was not present. Laboratory values revealed a hemoglobin value of 13 mg/dL and white blood cell count of 24.3 × 10 3/mm 3 with 78% neutrophils. The platelet count was 145,000/mm 3. His prothrombin time was 88 seconds; international normalized ratio (INR), 7; and activated partial thromboplastin time, 29.7 seconds. Arterial blood gas values, with room air, showed a pH of 7.28, PCO2 of 55 mm Hg, and PO2 of 61.3 mm Hg. A chest radiograph showed diffuse alveolar infiltrates (Fig. 1); it was confirmed with a chest computed tomographic scan (Fig. 2). The patient was diagnosed as having diffuse alveolar hemorrhage; supplemental oxygen, intravenous vitamin K, and fresh-frozen plasma (FFP) therapy was started in the emergency department. His respiratory failure did not progress, and intubation or mechanical ventilation was not required. The patient was discharged after hospitalization for 2 days in intensive care unit and for 7 days in cardiovascular surgery clinic.
☆ Prior publication: This article has not been published or submitted for publication elsewhere, in whole or in part, before submission to the American Journal of Emergency Medicine. ☆☆ Conflict of interest: We declared that we have no commercial, financial, and other relationships in any way related to the subject of this article all that might create any potential conflict of interest. 0735-6757/© 2014 Elsevier Inc. All rights reserved.
Warfarin is a coumarin derivative and acts by interfering with the cyclic interconversion of vitamin K and its 2.3 epoxide. Long-term oral warfarin therapy is indicated with some circumstances (eg, valve replacement, atrial fibrillation, etc), and patients are monitored with INR levels. Unfortunately, many factors such as diet, concurrent medication changes, poor compliance, or alcohol consumption may result in unexpected fluctuations in INR levels. The main complication of oral warfarin therapy is bleeding, especially from vital organs such as the brain or lung [2]. Diffuse alveolar hemorrhage usually presents with hemoptysis, anemia, hypoxemic respiratory failure, and infiltrates with an alveolar pattern on chest radiograph. Hemorrhage originates from the microvasculature instead of parenchyma or bronchial circulation. Most of the cases are secondary to pulmonary renal syndromes, connective tissue disorders, and drugs [3–5]. Although any epidemiologic study could not be found in the literature given the exact numbers of diffuse alveolar hemorrhage cases secondary to warfarin therapy, case reports or case series were reported rarely. Interestingly, cases without complication were treated successfully, and none of them died [6–10]. In a retrospective study, Oymak et al [11] reported on 11 patients with alveolar hemorrhage syndrome, and 7 of them died. In this study, only 1
Fig. 1. Chest radiograph of the patient showing diffuse alveolar infiltrates.
690.e4
E. Uysal et al. / American Journal of Emergency Medicine 32 (2014) 690.e3–690.e4
Süleyman Solak, MD Department of Emergency Medicine Bagcilar Training and Research Hospital Bağcılar Eğitim ve Araştırma Hastanesi, Bağcılar Istanbul, Turkey E-mail address: [email protected] Yahya Ayhan Acar, MD Department of Emergency Medicine Etimesgut Military Hospital, Etimesgut Asker Hastanesi Etimesgut, Ankara, Turkey E-mail address: [email protected] Mustafa Yalimol, MD Department of Emergency Medicine Bagcilar Training and Research Hospital Bağcılar Eğitim ve Araştırma Hastanesi Bağcılar, Istanbul, Turkey E-mail address: [email protected]
Fig. 2. Chest computed tomographic scan demonstrating bilateral alveolar infiltration.
patient died of warfarin overdose, but he had mitral valve stenosis and concomitant viral pneumonia with elevated sedimentation rate. Early recognition of pulmonary hemorrhage in anticoagulated patients is important because reversal of anticoagulation can be lifesaving [4]. For the rapid reversal of anticoagulation in case of serious bleeding, 10 mg of vitamin K1 should be given by slow intravenous infusion, supplemented with transfusion of fresh-frozen plasma [2]. Patients on long-term warfarin therapy have a potential risk for bleeding, and these complications can be seen in therapeutic ranges. Emergency physicians should consider bleeding in all anticoagulated patients and the importance of early recognition of pulmonary hemorrhage for the reversal of anticoagulation.
Emin Uysal, MD Department of Emergency Medicine Bagcilar Training and Research Hospital Bağcılar Eğitim ve Araştırma Hastanesi, Bağcılar Istanbul, Turkey E-mail address: [email protected] Erdem Çevik, MD Department of Emergency Medicine Van Military Hospital, Van Askeri Hastanesi Altıntepe, Van, Turkey E-mail address: [email protected]
http://dx.doi.org/10.1016/j.ajem.2013.12.022 References [1] Wysowski DK, Nourjah P, Swartz L. Bleeding complications with warfarin use: a prevalent adverse effect resulting in regulatory action. Arch Intern Med 2007;167 (13):1414–9. [2] Hirsh J, Fuster V, Ansell J, Halperin JL. American Heart Association/American College of Cardiology F. American Heart Association/American College of Cardiology Foundation guide to warfarin therapy. J Am Coll Cardiol 2003;41(9): 1633–52. [3] Albelda SM, Gefter WB, Epstein DM, Miller WT. Diffuse pulmonary hemorrhage: a review and classification. Radiology 1985;154(2):289–97. [4] Finley TN, Aronow A, Cosentino AM, Golde DW. Occult pulmonary hemorrhage in anticoagulated patients. Am J Respir Crit Care Med 1975;112(1):23–9. [5] Newsome BR, Morales JE. Diffuse alveolar hemorrhage. South Med J 2011;104(4): 269–74. [6] Barnett VT, Bergmann F, Humphrey H, Chediak J. Diffuse alveolar hemorrhage secondary to superwarfarin ingestion. Chest 1992;102(4):1301–2. [7] Itoh M, Oh-Ishi S, Nemoto K, Senba S, Adachi H, Kishi K, et al. A case of diffuse alveolar hemorrhage associated with tegafur plus uracil and warfarin therapy. Clinical medicine insights Case reports 2011;4:73–7. [8] Waness A, Aldabbagh T, Harakati M. Diffuse alveolar haemorrhage secondary to warfarin therapy for atrial fibrillation: a case report and literature review. BMJ case reports 2009 2009. [9] Erdogan D, Kocaman O, Oflaz H, Goren T. Alveolar hemorrhage associated with warfarin therapy: a case report and literature review. Int J Cardiovasc Imaging 2004;20(2):155–9. [10] Nural MS, Baydın A, Karataş AD, Elmalı M. Diffuse alveolar hemorrhage due to warfarin overdose. Toraks Dergisi 2006;7(1):68–71. [11] Oymak S, Tokgöz B, Akgün H, Gülmez İ, Erdoğan N, Demir R, et al. Alveolar hemorrhage syndromes; clinical, pathological, and imaging features: analysis of eleven patients. Toraks Dergisi 2002;3(1):52–8.
