however , its administration is associated with problems , such as the 
 adjustments needed to maintain an effective blood concentration .
in addition , dietary 
 restrictions are necessary , because vitamin k levels influence warfarin s efficacy . in 
 recent years , novel oral anticoagulants ( noacs )
those have demonstrated 
 encouraging outcomes , as well as effects comparable to those of warfarin . 

noacs are increasingly being used for primary and secondary 
 prevention with respect to cardiogenic embolisms . with the aging of society ,
elderly 
 patients suffering from atrial fibrillation make up a growing population . as a result ,
the 
 prevention of cardiogenic embolisms is becoming a major issue for social and health 
 economics .
since warfarin 
 has a long half - life , controlling intracranial bleeding is very difficult .
there are some 
 reports that the incidence of intracranial bleeding after noac administration is not as 
 frequent as in patients treated with warfarin . 

other reports indicate that the clinical course following intracranial hemorrhage is better 
 in noac patients than in warfarin patients .
we investigated the progress and prognosis of cases at our 
 institute in which conservative therapy was selected , with intracranial bleeding as a 
 complication during noac administration .
noacs were administered to 313 patients ( dabigatran : 173 , rivaroxaban : 140 ) at our 
 institute between 2011 and july 2014 .
all patients were diagnosed with non - valvular atrial 
 fibrillation and noac medication was started for the prevention of cardiogenic embolization . 

patients were allocated to dabigatran or rivaroxaban on the basis of their application time , 
 medication compliance , and other factors . random assignment was not performed . among these 
 patients ,
an 85-year - old man with a history of high - blood pressure , diabetes , and episodic atrial 
 fibrillation ( cardiac pacemaker ) was staying at a health and welfare institution for the 
 elderly because of dementia .
he was taking a hypoglycemic agent , -inhibitor , 
 anti - dementia drug , aspirin ( 100 mg per day ) , and dabigatran ( 220 mg per day ) .
he was 
 transported to our institute after the occurrence of left hemiparesis . on initial 
 examination ,
his level of consciousness was 10 points on the japan coma scale ( jcs 10 ) and 
 pupil diameters were equal at 2.5 mm bilaterally ; however , right conjugate deviation was 
 observed .
paralysis was observed in the left upper and lower limbs , and he scored 3/5 on a 
 manual muscle test .
his renal function indicated a creatinine clearance ( ccr ) of 49.6 
 ml / min .
an evaluation of the risk factors for cerebral stroke gave 3 points on the 
 congestive heart failure , hypertension , age , diabetes mellitus , and stroke / tia 
 ( chads2 ) scale , and 4 points on the congestive heart failure , 
 hypertension , age , diabetes mellitus , stroke / tia , vascular disease , age and sex category 
 ( cha2ds2-vasc ) scale , making him eligible for anticoagulant therapy .
at the same 
 time , his risk factors for bleeding during anticoagulant therapy produced a hypertension , 
 abnormal renal / liver function , stroke , bleeding history or predisposition , labile inr , 
 elderly , drug / alcohol use ( has - bled )   score of 2 points .
mild midline shift was observed on a 
 head computed tomography ( ct ) scan as a complication of subcortical bleeding in the right 
 frontal lobe ( figure 1afigure 1case 1 : the patient s head computed tomography on admission ( a ) and 7 days later 
 ( b ) . ) .
anticoagulant therapy ( dabigatran ) and antiplatelet therapy ( aspirin ) were 
 discontinued and conservative therapy was applied .
the level of consciousness shifted to 
 jcs 3 without aggravation of the cerebral hemorrhage ( figure 1b ) .
the patient was transferred to a nursing home 10 months after 
 the onset of cerebral hemorrhage and the discontinuation of anticoagulant therapy .
case 1 : the patient s head computed tomography on admission ( a ) and 7 days later 
 ( b ) . an 81-year - old man with a history of cerebral infarction , diabetes , and atrial 
 fibrillation was treated with insulin and rivaroxaban ( 10 mg per day ) .
a residual 
 disability caused by cerebral infarction left him requiring total assistance in his 
 day - to - day living .
he was admitted because of torso tilt and vomiting . on initial 
 examination , his consciousness level was jcs 3 with no apparent immobility of the pupils , 
 deviation , or paralysis of the four limbs .
regarding risk factors for 
 cerebral stroke , his chads2 score was 4 points and 
 cha2ds2-vasc was 5 points .
at the same time , the has - bled score 
 was 2 points , with the risk of bleeding during anticoagulant therapy determined as 
 moderate .
a head ct scan indicated a left cerebellar hemorrhage ( figure 2afigure 2case 2 : the patient s head computed tomography on admission ( a ) and 5 days later 
 ( b ) . ) . anticoagulant therapy
the patient was transferred to a geriatric health services 
 facility 3 months after the onset of cerebellar hemorrhage while still receiving no 
 anticoagulant therapy .
case 2 : the patient s head computed tomography on admission ( a ) and 5 days later 
 ( b ) .
an 85-year - old man with a history of high - blood pressure , diabetes , and episodic atrial 
 fibrillation ( cardiac pacemaker ) was staying at a health and welfare institution for the 
 elderly because of dementia .
he was taking a hypoglycemic agent , -inhibitor , 
 anti - dementia drug , aspirin ( 100 mg per day ) , and dabigatran ( 220 mg per day ) .
he was 
 transported to our institute after the occurrence of left hemiparesis . on initial 
 examination ,
his level of consciousness was 10 points on the japan coma scale ( jcs 10 ) and 
 pupil diameters were equal at 2.5 mm bilaterally ; however , right conjugate deviation was 
 observed .
paralysis was observed in the left upper and lower limbs , and he scored 3/5 on a 
 manual muscle test .
his renal function indicated a creatinine clearance ( ccr ) of 49.6 
 ml / min .
an evaluation of the risk factors for cerebral stroke gave 3 points on the 
 congestive heart failure , hypertension , age , diabetes mellitus , and stroke / tia 
 ( chads2 ) scale , and 4 points on the congestive heart failure , 
 hypertension , age , diabetes mellitus , stroke / tia , vascular disease , age and sex category 
 ( cha2ds2-vasc ) scale , making him eligible for anticoagulant therapy .
at the same 
 time , his risk factors for bleeding during anticoagulant therapy produced a hypertension , 
 abnormal renal / liver function , stroke , bleeding history or predisposition , labile inr , 
 elderly , drug / alcohol use ( has - bled )   score of 2 points .
mild midline shift was observed on a 
 head computed tomography ( ct ) scan as a complication of subcortical bleeding in the right 
 frontal lobe ( figure 1afigure 1case 1 : the patient s head computed tomography on admission ( a ) and 7 days later 
 ( b ) . ) .
anticoagulant therapy ( dabigatran ) and antiplatelet therapy ( aspirin ) were 
 discontinued and conservative therapy was applied .
the level of consciousness shifted to 
 jcs 3 without aggravation of the cerebral hemorrhage ( figure 1b ) .
the patient was transferred to a nursing home 10 months after 
 the onset of cerebral hemorrhage and the discontinuation of anticoagulant therapy .
case 1 : the patient s head computed tomography on admission ( a ) and 7 days later 
 ( b ) .
an 81-year - old man with a history of cerebral infarction , diabetes , and atrial 
 fibrillation was treated with insulin and rivaroxaban ( 10 mg per day ) .
a residual 
 disability caused by cerebral infarction left him requiring total assistance in his 
 day - to - day living .
he was admitted because of torso tilt and vomiting . on initial 
 examination , his consciousness level was jcs 3 with no apparent immobility of the pupils , 
 deviation , or paralysis of the four limbs .
regarding risk factors for 
 cerebral stroke , his chads2 score was 4 points and 
 cha2ds2-vasc was 5 points .
at the same time , the has - bled score 
 was 2 points , with the risk of bleeding during anticoagulant therapy determined as 
 moderate .
a head ct scan indicated a left cerebellar hemorrhage ( figure 2afigure 2case 2 : the patient s head computed tomography on admission ( a ) and 5 days later 
 ( b ) . ) .
the patient was transferred to a geriatric health services 
 facility 3 months after the onset of cerebellar hemorrhage while still receiving no 
 anticoagulant therapy .
case 2 : the patient s head computed tomography on admission ( a ) and 5 days later 
 ( b ) .
among the 313 patients treated with noac at our institute between 2011 and july 2014 
 ( dabigatran : 173 , rivaroxaban : 140 ) the average age was 74.6 years , with 96 patients aged up 
 to 70 years and 217 aged 71 years or older .
regarding 
 chads2 , 54 patients scored 01 point , while 259 scored 2 points or more .
the 
 cha2ds2-vasc score was 01 point in 24 cases and 2 points or more in 
 289 cases .
serious complications requiring discontinuation of anticoagulant therapy occurred 
 in 9 cases , of which intracranial bleeding was observed in 2 .
in addition , recurrence of 
 cerebral infarction was observed in 8 cases . the intracranial bleeding involved hemorrhage 
 in the cerebral parenchyma ( 1 case of cerebral hemorrhage in the cerebrum and 1 case of 
 cerebellar hemorrhage ) , with no cases of subdural bleeding .
conservative therapy was 
 selected in both intracranial hemorrhage cases ; no aggravation of hematoma was observed as a 
 result of the antihypertensive therapy , the administration of a hemostatic drug , and the 
 discontinuation of anticoagulants .
i have described above two cases in which the administration of anticoagulants was 
 indicated ( chads2 and cha2ds2-vasc scores of 2 points or 
 more ) and intracranial hemorrhage was observed as a complication during noac administration . 

the bleeding risk in both cases was moderate ( has - bled score 2 points ) .
however , no increase 
 in the quantity of hematoma or aggravation of the abnormal neurological findings were 
 observed as a result of conservative therapy . whereas the half - life of warfarin in serum is 
 considered to be 20 to 60 hours , the half - lives of 1217 hours for dabigatran and 59 hours 
 for rivaroxaban mean that the anticoagulant effect of noac is likely to disappear within a 
 very short period of time following withdrawal .
in addition , in noac the mechanism of 
 coagulation inhibition and hemostasis differs from that of warfarin , being limited to a 
 single cause ( figure 3figure 3mechanism of hemostasis and targets of warfarin and novel oral anticoagulants . ) .
furthermore , the brain system is rich in tissue factor , which contributes to the 
 activation of the extrinsic clotting system due to factor vii . unlike warfarin ,
the 
 microenvironment of the hemorrhaged brain system contains abundant active factor vii in 
 patients taking noac .
therefore , the rapid functional restoration of the coagulation and 
 hemostasis mechanisms occurs in parallel with the decline in blood concentration once the 
 noac intake is stopped .
thus , the increase in hematoma size can be controlled by rapid 
 withdrawal alone , even after the onset of intracranial bleeding .
a comparative outcome analysis has indicated that noac have a lower incidence of 
 complications such as massive bleeding or intracranial bleeding .
substantial anticoagulant 
 effects in preventing cerebral infarction and systemic embolisms have been 
 reported , 
 .
although intracranial bleeding 
 during anticoagulant therapy is likely to become serious , no sudden increase in the hematoma 
 is observed , because of the short half - lives of noac in blood compared to that of warfarin . 
 in cases with a high anticoagulant therapy recommendation score ( chads2 and 
 cha2ds2-vasc )
currently , in japan , the suitability of drugs is limited to 
 inhibiting the occurrence of ischemic cerebral stroke and systemic embolisms in patients 
 with non - valvular atrial fibrillation . based on our results and a previous report ,
noac are more likely than 
 warfarin to inhibit an increase in severity at the onset of hemorrhagic complications .
the has - bled score is usually used for the prediction of the risk of intracranial 
 hemorrhage during anticoagulation therapy .
however , a moderate 
 has - bled score has not been established as a prognostic factor .
the relationship between 
 has - bled score and hematoma size or prognosis needs to be investigated by accumulating more 
 patient cases and performing a statistical analysis .
, the number of elderly patients developing atrial 
 fibrillation as underlying disease is expected to increase .
accordingly , for the purposes of 
 primary and secondary prevention , the expansion of the range of diseases suitable for 
 anticoagulant therapy can not be avoided .
against such a social background , it has been 
 predicted that cases of intracranial bleeding during anticoagulant therapy will continue to 
 increase in the future .
although the use of noac may be limited by social and health 
 economic backgrounds , along with the limitation of pharmaceutical registration , the types of 
 disease suitable for anticoagulant treatment are likely to increase .
since noac have the 
 advantage of not worsening the severity of serious complications , they may be useful in the 
 management of patients with atrial fibrillation .
 objective : oral anticoagulants are widely administered to patients with 
 atrial fibrillation in order to prevent the onset of cardiogenic embolisms . however , 
 intracranial bleeding during anticoagulant therapy often leads to fatal outcomes . 
 
 accordingly , the use of novel oral anticoagulants ( noacs ) , which less frequently have 
 intracranial bleeding as a complication , is expanding . a nationwide survey of intracranial 
 bleeding and its prognosis in japan reported that intracranial bleeding of advanced 
 severity was not common after noac administration . 
 in this report , two cases from our 
 institute are presented.patients : case 1 was an 85-year - old man with a right frontal lobe hemorrhage 
 while under dabigatran therapy . 
 case 2 was an 81-year - old man who had cerebellar 
 hemorrhage while under rivaroxaban therapy.result : in both patients , the clinical course progressed without aggravation 
 of bleeding or neurological abnormalities once anticoagulant therapy was discontinued.conclusion : these observations suggest that intracranial hemorrhage during 
 noac therapy is easily controlled by discontinuation of the drug . 
 noac administration may 
 therefore be appropriate despite the risk of such severe complications . 
 further case 
 studies that include a subgroup analysis with respect to each noac or patient background 
 will be required to establish appropriate guidelines for the prevention of cardiogenic 
 embolisms in patients with atrial fibrillation . 
Introduction
Materials and Methods
Case Presentations
Case 1
Case 2
Results
Discussion