398 Case report
Spontaneous epidural and subdural hematoma in a child with afibrinogenemia and postoperative management Asiyan Kilit Y.a, Yontem Yamanb, Rana Isguderc, Ozgur Cartıb, Bengu Demiragb, Hasan Aginc, Gulcihan Ozekb, Burcak Gunes Tatlıb, Esin Albudakb and Emel Berksoyd Congenital afibrinogenemia is a rare coagulation disorder that exhibits recessive inheritance. The prevalence of this disease is around 1 per 1 000 000, but it is increased in countries where consanguineous marriages are common. Umbilical cord bleeding during the neonatal period is generally the first manifestation of the disease, but a later age of onset is not uncommon. This disease may also be manifested by gastrointestinal, genitourinary, mucosal, muscular, articular, and intracranial bleeding during childhood. Intracranial hemorrhage is a rare condition, but it is the leading cause of death in patients with afibrinogenemia. In this report, we present the case of a 13-year-old female patient with afibrinogenemia who underwent an operation for spontaneous massive extradural and subdural hematoma. Blood Coagul
Introduction Congenital afibrinogenemia is a rare coagulation disorder exhibiting recessive inheritance with three genes located in chromosome 4q. In order to be afibrinogenemic, the patient must have two affected alleles, either homozygous or compound heterozygous [1]. In the absence of consumption coagulopathy, an infinitesimally low level of fibrinogen is used as a diagnostic sign in this disease. Afibrinogenemia generally causes bleeding in newborns, with 85% of the cases having umbilical cord bleeding [2]. The frequency of mucosal type bleeding symptoms is higher in afibrinogenemia than in hemophilia, but joint and muscle bleeding are less frequent and severe [1]. The first manifestation of this disease may be seen as gastrointestinal, genitourinary, mucosal, or intracranial bleeding during childhood [3]. Intracranial hemorrhage is the leading cause of death [3]. A small number of patients with spontaneous intracranial bleeding beyond the neonatal period have been reported, but none of these patients underwent surgery [4]. Herein, we present the case of a 13-year-old girl who underwent surgery for spontaneous massive extradural and subdural hematomas. This case is an important addition to the literature as afibrinogenemia-related intracerebral hemorrhage is a rare condition, and there are few children who have undergone cranial surgery for afibrinogenemia.
Case report A 13-year-old girl was admitted to the emergency room with loss of consciousness. She had a headache and was 0957-5235 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
Fibrinolysis 25:398–400 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Blood Coagulation and Fibrinolysis 2014, 25:398–400 Keywords: afibrinogenemia, coagulation disorder, intracranial hematoma a
Department of Neurosurgery, bDepartment of Pediatric Hematology-Oncology, Department of Pediatric Intensive Care Unit and dDepartment of Pediatric Emergency, ˙Izmir Behcet Uz Children’s Training and Research Hospital, Izmir, Turkey c
Correspondence to Asiyan Kilit Y., MD, Assistant Professor, Department of Neurosurgery, Izmir Behcet Uz Children’s Training and Research Hospital, Izmir, Turkey Tel: +90 232 489 56 56; fax: +90 232 489 23 15; e-mail: [email protected] Received 7 October 2013 Accepted 1 December 2013
vomiting the day before she was admitted. She had been diagnosed with afibrinogenemia at 7 years of age with nasal bleeding. Her medical history indicated that she had experienced umbilical cord bleeding and some mucosal hemorrhage. She had received cryoprecipitate twice before the age of 13 for mucosal hemorrhages. Her parents were consanguineous. She had two brothers with afibrinogenemia who passed away. One of her brothers died of intracranial bleeding at 21 years of age, whereas the other died of catastrophic umbilical cord bleeding at 3 days of age. The general condition of the patient was poor and her breath was superficial. Her vital signs were as follows: temperature of 35.68C, blood pressure (BP) of 131/92 mmHg, pulse of 63 per min, respiratory rate of 14 per min, and oxygen saturation of 90% on 3 l/min nasal cannula. Her Glasgow coma scale was 4 out of 15 (eyes: 1, motor: 2, and verbal: 1). Her pupils were anisocoric, and the right pupil was dilated. Direct and indirect light reflexes were bilaterally negative. She also had motor dysfunction, neck stiffness, and facial asymmetry. After intubation, we began mechanical ventilation and 20 cc/kg of fresh frozen plasma (FFP) was administered, as cryoprecipitate and purified fibrinogen concentrate (Haemocompletan) were not available in our hospital at that time. Urgent computed tomography (CT) scanning of the brain was obtained. A laboratory examination (obtained when she arrived at the hospital) revealed the following: hemoglobin: 9.6 g/dl, total leucocyte: 23 200/ml, platelet count: 380 000/ml, prothrombin time (PT): DOI:10.1097/MBC.0000000000000049
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Spontaneous epidural and subdural hematoma Kilit et al. 399
12–14.5 s, and partial thromboplastin time (PTT): 32–35.6 s over 2 min. Her plasma fibrinogen level was undetectable as determined by a functional assay, but her renal and hepatic function tests were within the normal limits. Cranial CT scanning revealed 5 cm 9 cm acute epidural bleeding in the right frontal region and a midline shift (Fig. 1). The patient underwent emergency surgery without obtaining control blood coagulation tests. The epidural hematoma and preoperatively detected subdural hematoma were drained by a right craniotomy. We obtained fibrinogen concentrate, and the patient was infused with a dose of 100 mg/kg at the end of the operation. Her pupils returned to their normal size after the operation. Light reflexes were taken. One hour postoperatively, her hemoglobin was 9.2 g/dl, platelet count was 185 000/ml, PT was 18.9 s, activated partial thromboplastin time (APTT) was greater than 2 min, and fibrinogen was 2.51 g/l. However, she developed new symptoms 18 h after the operation. A CT scan revealed an epidural hematoma that reached 18 mm at its widest point in the right occipital lobe which caused us to perform another operation. Preoperative values were as follows: hemoglobin – 8.8 g/dl, total leucocyte – 9900/ml, platelet count – 147 000/ml, PT – 17.2 s, APTT – 29.4 s, and fibrinogen – 1.96 g/l. The hematoma was drained by a second operation. She was followed up within the pediatric ICU. She developed hypocapnia (as determined by end-tidal CO2 monitoring) while under mechanical ventilation and Fig. 1
she was hypotensive during intensive care follow-up. Her vital symptoms stabilized. Six hours later, the patient was extubated. Twelve hours after the surgery, cranial CT scan showed she had no operative neurosurgical disorder (Fig. 2). She recovered from the ICU without neurological deficit. During her first 14 postoperative days, she underwent fibrinogen infusion with cryoprecipitate twice because we had difficulty in obtaining Haemocomplettan. Then, she was administered Haemocomplettan in order to maintain fibrinogen levels above 1.5 g/l for the first four postoperative days and 1 g/l thereafter. After the 14th postoperative day, when her wounds healed, fibrinogen infusion was performed in order to maintain fibrinogen levels above 0.5 g/l. She was prescribed Haemocompletan at a dosage of 60 mg/kg per week for prophylaxis to prevent new bleeding. Bleeding or thrombosis did not occur in the 11 months’ follow-up period.
Discussion Spontaneous epidural bleeding is rare. It is mostly seen in patients with chronic renal failure who frequently undergo dialysis, and it is often seen during open heart surgery. It has also been reported to occur in conditions such as middle meningeal artery aneurysm, systemic lupus erythematosus, orbital cellulitis, chronic otitis media, and homozygous sickle cell anemia [5]. The incidence of spontaneous intracerebral hemorrhage is unknown in children with afibrinogenemia. Fibrinogen is a 340-kDa fibrous glycoprotein that is synthesized in the liver [6]. It is normally found in plasma at a Fig. 2
Acute epidural and subdural bleeding in the right frontal region, and a midline shift.
CT image after the second operation. CT, computed tomography.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
400 Blood Coagulation and Fibrinolysis 2014, Vol 25 No 4
concentration of 1.5–3.5 g/l. Its molecular length is 45 nm and its half-life is 4 days. Fifty percent of the cases with congenital afibrinogenemia have consanguineous parents. Afibrinogenemia and hypofibrinogenemia-related spontaneous epidural hematoma are rare, as the literature shows that only two cases have undergone craniotomy using fibrinogen. One of the patients was a 5-year-old boy with hypofibrinogenemia and the other was a 32-year-old woman with afibrinogenemia [5,7]. As in our case, we believe that these spontaneous epidural hematomas were induced by the near absence of fibrinogen in the blood. Fibrinogen replacement (at a level of 1.5 g/l) is recommended before surgery to prevent perioperative bleeding in cases with afibrinogenemia-related intracranial bleeding [8]. In addition, plasma fibrinogen levels are recommended to be maintained at 1.0 g/l for 4–14 days [4]. After the 14th day, fibrinogen infusion is recommended to maintain fibrinogen levels above 0.5 g/l until wound healing occurs [8]. With these approaches, children with spontaneous epidural hematoma can be successfully operated on. However, as the actual half-life of fibrinogen varies between individuals, dose adjustments must be made according to the current blood level of fibrinogen [9]. Epidural hematoma is a type of bleeding with a high risk of being herniated when it is not immediately operated on. It has been reported that FFP and cryoprecipitate should be used in urgent cases where fibrinogen is not available [10]. As cryoprecipitate and fibrinogen were not available to us, the operation was performed by administering FFP to our patient, because the time it would take to procure the correct supplies might increase her mortality. In conclusion, children with afibrinogenemia may exhibit spontaneous intracranial bleeding. Fibrinogen replacement before the surgery must be planned in consultation with a pediatric hematologist [11]. Fibrinogen replacement therapy should be performed in all afibrinogenemic patients with hemorrhage. Cryoprecipitate, FFP, and lyophilized fibrinogen concentrates are the sources for replacement therapy. However, the dose for fibrinogen concentrate and targeted plasma levels of fibrinogen have not been optimized. Fibrinogen concentrates are safer than cryoprecipitates, and furthermore, precise dosing can be done with fibrinogen concentrate because their potency is known [11]. No data are available on the effective prophylactic levels of fibrinogen. Primary prophylaxis in afibrinogenemic
patients is not advised because of the risk of thrombosis. Data with secondary prophylactic treatment in these patients is very limited, and therefore the optimal duration is not known [10]. However, the recurrence of intracerebral hemorrhage within several months in patients with afibrinogenemia justifies the prolongation of substitution therapy. The benefits of continuing prophylactic fibrinogen substitution should be weighed against the risk of possible complications. As our patient’s congenital and acquired thrombophilic risk factors were negative, we decided to give Haemocomplettan at a dose of 60 mg/kg per week for prophylaxis in order to prevent new bleeding lifelong. In our patient, bleeding or thrombosis did not occur in the 11 months’ follow-up period. Finally, as intracerebral hemorrhage is a life-threatening condition, substitution therapy must be installed promptly at presentation before additional tests are performed. Long-term secondary prophylaxis with purified fibrinogen concentrate in a patient who did not have thrombophilic risk factors appears to be effective and well tolerated.
Acknowledgements Conflicts of interest
There are no conflicts of interest.
References 1
2 3
4
5
6 7
8
9
10
11
Lak M, Keihani M, Elahi F, Peyvandi F, Mannucci PM. Bleeding and thrombosis in 55 patients with inherited afibrinogenaemia. Br J Haematol 1999; 107:204–206. Acharya SS, Dimichele DM. Rare inherited disorders of fibrinogen. Haemophilia 2007; 14:1151–1158. Peyvandi F, Haertel S, Knaub S, Mannucci PM. Incidence of bleeding symptoms in 100 patients with inherited afibrinogenemia or hypofibrinogenemia. J Thromb Haemost 2006; 4:1634–1637. Bornikova L, Peyvandi F, Allen G, Bernstein J, Manco-Johnson MJ. Fibrinogen replacement therapy for congenital fibrinogen deficiency. J Thromb Haemost 2011; 9:1687–1704. Pati S, Kombogiorgas D, Anwar A, Price RF. Spontaneous extra-axial intracranial hemorrhage followed by thrombosis in congenital afibrinogenemia: perioperative management of this rare combination. Surg Neurol 2009; 71:689–692. Mosesson MW, Siebenlist KR, Meh DA. The structure and biological features of fibrinogen and fibrin. Ann N Y Acad Sci 2001; 936:11–30. Bay A, Coskun E, Leblebisatan G, Sivasli E. Epidural hematoma and cephalohematoma with congenital hypofibrinogenemia. Blood Coagul Fibrinolysis 2012; 23:229–231. Bolton-Maggs PH, Perry DJ, Chalmers EA, Parapia LA, Wilde JT, Williams MD. The rare coagulation disorders – review with guidelines for management from the United Kingdom Hemophilia Centre Doctors’ Organization. Hemophilia 2004; 10:593–628. Henselmans JML, Meijer K, Haaxma R, Hew J, van der Meer J. Recurrent spontaneous intracerebral hemorrhage in a congenitally afibrinogenemic patient. Diagnostic pitfalls and therapeutic options. Stroke 1999; 30:2479–2482. Tziomalos K, Vakalopoulou S, Perifanis V, Garipidou V. Treatment of congenital fibrinogen deficiency: overview and recent findings. Vasc Health Risk Manag 2009; 5:843–848. Peyvandi F, Bolton-Maggs PH, Batorova A, De Moerloose P. Rare bleeding disorders. Hemophilia 2012; 18:148–153.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Spontaneous epidural and subdural hematoma in a child with afibrinogenemia and postoperative management Asiyan Kilit Y.a, Yontem Yamanb, Rana Isguderc, Ozgur Cartıb, Bengu Demiragb, Hasan Aginc, Gulcihan Ozekb, Burcak Gunes Tatlıb, Esin Albudakb and Emel Berksoyd Congenital afibrinogenemia is a rare coagulation disorder that exhibits recessive inheritance. The prevalence of this disease is around 1 per 1 000 000, but it is increased in countries where consanguineous marriages are common. Umbilical cord bleeding during the neonatal period is generally the first manifestation of the disease, but a later age of onset is not uncommon. This disease may also be manifested by gastrointestinal, genitourinary, mucosal, muscular, articular, and intracranial bleeding during childhood. Intracranial hemorrhage is a rare condition, but it is the leading cause of death in patients with afibrinogenemia. In this report, we present the case of a 13-year-old female patient with afibrinogenemia who underwent an operation for spontaneous massive extradural and subdural hematoma. Blood Coagul
Introduction Congenital afibrinogenemia is a rare coagulation disorder exhibiting recessive inheritance with three genes located in chromosome 4q. In order to be afibrinogenemic, the patient must have two affected alleles, either homozygous or compound heterozygous [1]. In the absence of consumption coagulopathy, an infinitesimally low level of fibrinogen is used as a diagnostic sign in this disease. Afibrinogenemia generally causes bleeding in newborns, with 85% of the cases having umbilical cord bleeding [2]. The frequency of mucosal type bleeding symptoms is higher in afibrinogenemia than in hemophilia, but joint and muscle bleeding are less frequent and severe [1]. The first manifestation of this disease may be seen as gastrointestinal, genitourinary, mucosal, or intracranial bleeding during childhood [3]. Intracranial hemorrhage is the leading cause of death [3]. A small number of patients with spontaneous intracranial bleeding beyond the neonatal period have been reported, but none of these patients underwent surgery [4]. Herein, we present the case of a 13-year-old girl who underwent surgery for spontaneous massive extradural and subdural hematomas. This case is an important addition to the literature as afibrinogenemia-related intracerebral hemorrhage is a rare condition, and there are few children who have undergone cranial surgery for afibrinogenemia.
Case report A 13-year-old girl was admitted to the emergency room with loss of consciousness. She had a headache and was 0957-5235 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
Fibrinolysis 25:398–400 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Blood Coagulation and Fibrinolysis 2014, 25:398–400 Keywords: afibrinogenemia, coagulation disorder, intracranial hematoma a
Department of Neurosurgery, bDepartment of Pediatric Hematology-Oncology, Department of Pediatric Intensive Care Unit and dDepartment of Pediatric Emergency, ˙Izmir Behcet Uz Children’s Training and Research Hospital, Izmir, Turkey c
Correspondence to Asiyan Kilit Y., MD, Assistant Professor, Department of Neurosurgery, Izmir Behcet Uz Children’s Training and Research Hospital, Izmir, Turkey Tel: +90 232 489 56 56; fax: +90 232 489 23 15; e-mail: [email protected] Received 7 October 2013 Accepted 1 December 2013
vomiting the day before she was admitted. She had been diagnosed with afibrinogenemia at 7 years of age with nasal bleeding. Her medical history indicated that she had experienced umbilical cord bleeding and some mucosal hemorrhage. She had received cryoprecipitate twice before the age of 13 for mucosal hemorrhages. Her parents were consanguineous. She had two brothers with afibrinogenemia who passed away. One of her brothers died of intracranial bleeding at 21 years of age, whereas the other died of catastrophic umbilical cord bleeding at 3 days of age. The general condition of the patient was poor and her breath was superficial. Her vital signs were as follows: temperature of 35.68C, blood pressure (BP) of 131/92 mmHg, pulse of 63 per min, respiratory rate of 14 per min, and oxygen saturation of 90% on 3 l/min nasal cannula. Her Glasgow coma scale was 4 out of 15 (eyes: 1, motor: 2, and verbal: 1). Her pupils were anisocoric, and the right pupil was dilated. Direct and indirect light reflexes were bilaterally negative. She also had motor dysfunction, neck stiffness, and facial asymmetry. After intubation, we began mechanical ventilation and 20 cc/kg of fresh frozen plasma (FFP) was administered, as cryoprecipitate and purified fibrinogen concentrate (Haemocompletan) were not available in our hospital at that time. Urgent computed tomography (CT) scanning of the brain was obtained. A laboratory examination (obtained when she arrived at the hospital) revealed the following: hemoglobin: 9.6 g/dl, total leucocyte: 23 200/ml, platelet count: 380 000/ml, prothrombin time (PT): DOI:10.1097/MBC.0000000000000049
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Spontaneous epidural and subdural hematoma Kilit et al. 399
12–14.5 s, and partial thromboplastin time (PTT): 32–35.6 s over 2 min. Her plasma fibrinogen level was undetectable as determined by a functional assay, but her renal and hepatic function tests were within the normal limits. Cranial CT scanning revealed 5 cm 9 cm acute epidural bleeding in the right frontal region and a midline shift (Fig. 1). The patient underwent emergency surgery without obtaining control blood coagulation tests. The epidural hematoma and preoperatively detected subdural hematoma were drained by a right craniotomy. We obtained fibrinogen concentrate, and the patient was infused with a dose of 100 mg/kg at the end of the operation. Her pupils returned to their normal size after the operation. Light reflexes were taken. One hour postoperatively, her hemoglobin was 9.2 g/dl, platelet count was 185 000/ml, PT was 18.9 s, activated partial thromboplastin time (APTT) was greater than 2 min, and fibrinogen was 2.51 g/l. However, she developed new symptoms 18 h after the operation. A CT scan revealed an epidural hematoma that reached 18 mm at its widest point in the right occipital lobe which caused us to perform another operation. Preoperative values were as follows: hemoglobin – 8.8 g/dl, total leucocyte – 9900/ml, platelet count – 147 000/ml, PT – 17.2 s, APTT – 29.4 s, and fibrinogen – 1.96 g/l. The hematoma was drained by a second operation. She was followed up within the pediatric ICU. She developed hypocapnia (as determined by end-tidal CO2 monitoring) while under mechanical ventilation and Fig. 1
she was hypotensive during intensive care follow-up. Her vital symptoms stabilized. Six hours later, the patient was extubated. Twelve hours after the surgery, cranial CT scan showed she had no operative neurosurgical disorder (Fig. 2). She recovered from the ICU without neurological deficit. During her first 14 postoperative days, she underwent fibrinogen infusion with cryoprecipitate twice because we had difficulty in obtaining Haemocomplettan. Then, she was administered Haemocomplettan in order to maintain fibrinogen levels above 1.5 g/l for the first four postoperative days and 1 g/l thereafter. After the 14th postoperative day, when her wounds healed, fibrinogen infusion was performed in order to maintain fibrinogen levels above 0.5 g/l. She was prescribed Haemocompletan at a dosage of 60 mg/kg per week for prophylaxis to prevent new bleeding. Bleeding or thrombosis did not occur in the 11 months’ follow-up period.
Discussion Spontaneous epidural bleeding is rare. It is mostly seen in patients with chronic renal failure who frequently undergo dialysis, and it is often seen during open heart surgery. It has also been reported to occur in conditions such as middle meningeal artery aneurysm, systemic lupus erythematosus, orbital cellulitis, chronic otitis media, and homozygous sickle cell anemia [5]. The incidence of spontaneous intracerebral hemorrhage is unknown in children with afibrinogenemia. Fibrinogen is a 340-kDa fibrous glycoprotein that is synthesized in the liver [6]. It is normally found in plasma at a Fig. 2
Acute epidural and subdural bleeding in the right frontal region, and a midline shift.
CT image after the second operation. CT, computed tomography.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
400 Blood Coagulation and Fibrinolysis 2014, Vol 25 No 4
concentration of 1.5–3.5 g/l. Its molecular length is 45 nm and its half-life is 4 days. Fifty percent of the cases with congenital afibrinogenemia have consanguineous parents. Afibrinogenemia and hypofibrinogenemia-related spontaneous epidural hematoma are rare, as the literature shows that only two cases have undergone craniotomy using fibrinogen. One of the patients was a 5-year-old boy with hypofibrinogenemia and the other was a 32-year-old woman with afibrinogenemia [5,7]. As in our case, we believe that these spontaneous epidural hematomas were induced by the near absence of fibrinogen in the blood. Fibrinogen replacement (at a level of 1.5 g/l) is recommended before surgery to prevent perioperative bleeding in cases with afibrinogenemia-related intracranial bleeding [8]. In addition, plasma fibrinogen levels are recommended to be maintained at 1.0 g/l for 4–14 days [4]. After the 14th day, fibrinogen infusion is recommended to maintain fibrinogen levels above 0.5 g/l until wound healing occurs [8]. With these approaches, children with spontaneous epidural hematoma can be successfully operated on. However, as the actual half-life of fibrinogen varies between individuals, dose adjustments must be made according to the current blood level of fibrinogen [9]. Epidural hematoma is a type of bleeding with a high risk of being herniated when it is not immediately operated on. It has been reported that FFP and cryoprecipitate should be used in urgent cases where fibrinogen is not available [10]. As cryoprecipitate and fibrinogen were not available to us, the operation was performed by administering FFP to our patient, because the time it would take to procure the correct supplies might increase her mortality. In conclusion, children with afibrinogenemia may exhibit spontaneous intracranial bleeding. Fibrinogen replacement before the surgery must be planned in consultation with a pediatric hematologist [11]. Fibrinogen replacement therapy should be performed in all afibrinogenemic patients with hemorrhage. Cryoprecipitate, FFP, and lyophilized fibrinogen concentrates are the sources for replacement therapy. However, the dose for fibrinogen concentrate and targeted plasma levels of fibrinogen have not been optimized. Fibrinogen concentrates are safer than cryoprecipitates, and furthermore, precise dosing can be done with fibrinogen concentrate because their potency is known [11]. No data are available on the effective prophylactic levels of fibrinogen. Primary prophylaxis in afibrinogenemic
patients is not advised because of the risk of thrombosis. Data with secondary prophylactic treatment in these patients is very limited, and therefore the optimal duration is not known [10]. However, the recurrence of intracerebral hemorrhage within several months in patients with afibrinogenemia justifies the prolongation of substitution therapy. The benefits of continuing prophylactic fibrinogen substitution should be weighed against the risk of possible complications. As our patient’s congenital and acquired thrombophilic risk factors were negative, we decided to give Haemocomplettan at a dose of 60 mg/kg per week for prophylaxis in order to prevent new bleeding lifelong. In our patient, bleeding or thrombosis did not occur in the 11 months’ follow-up period. Finally, as intracerebral hemorrhage is a life-threatening condition, substitution therapy must be installed promptly at presentation before additional tests are performed. Long-term secondary prophylaxis with purified fibrinogen concentrate in a patient who did not have thrombophilic risk factors appears to be effective and well tolerated.
Acknowledgements Conflicts of interest
There are no conflicts of interest.
References 1
2 3
4
5
6 7
8
9
10
11
Lak M, Keihani M, Elahi F, Peyvandi F, Mannucci PM. Bleeding and thrombosis in 55 patients with inherited afibrinogenaemia. Br J Haematol 1999; 107:204–206. Acharya SS, Dimichele DM. Rare inherited disorders of fibrinogen. Haemophilia 2007; 14:1151–1158. Peyvandi F, Haertel S, Knaub S, Mannucci PM. Incidence of bleeding symptoms in 100 patients with inherited afibrinogenemia or hypofibrinogenemia. J Thromb Haemost 2006; 4:1634–1637. Bornikova L, Peyvandi F, Allen G, Bernstein J, Manco-Johnson MJ. Fibrinogen replacement therapy for congenital fibrinogen deficiency. J Thromb Haemost 2011; 9:1687–1704. Pati S, Kombogiorgas D, Anwar A, Price RF. Spontaneous extra-axial intracranial hemorrhage followed by thrombosis in congenital afibrinogenemia: perioperative management of this rare combination. Surg Neurol 2009; 71:689–692. Mosesson MW, Siebenlist KR, Meh DA. The structure and biological features of fibrinogen and fibrin. Ann N Y Acad Sci 2001; 936:11–30. Bay A, Coskun E, Leblebisatan G, Sivasli E. Epidural hematoma and cephalohematoma with congenital hypofibrinogenemia. Blood Coagul Fibrinolysis 2012; 23:229–231. Bolton-Maggs PH, Perry DJ, Chalmers EA, Parapia LA, Wilde JT, Williams MD. The rare coagulation disorders – review with guidelines for management from the United Kingdom Hemophilia Centre Doctors’ Organization. Hemophilia 2004; 10:593–628. Henselmans JML, Meijer K, Haaxma R, Hew J, van der Meer J. Recurrent spontaneous intracerebral hemorrhage in a congenitally afibrinogenemic patient. Diagnostic pitfalls and therapeutic options. Stroke 1999; 30:2479–2482. Tziomalos K, Vakalopoulou S, Perifanis V, Garipidou V. Treatment of congenital fibrinogen deficiency: overview and recent findings. Vasc Health Risk Manag 2009; 5:843–848. Peyvandi F, Bolton-Maggs PH, Batorova A, De Moerloose P. Rare bleeding disorders. Hemophilia 2012; 18:148–153.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
