Intracranial Hemorrhage Outcome Research Articles

Lack of Aquaporin 9 Reduces Brain Angiogenesis and Exaggerates Neuronal Loss in the Hippocampus Following Intracranial Hemorrhage in Mice.

Intracranial hemorrhage (ICH) is a common subtype of stroke with high morbidity and mortality. However, few clinical therapies that can reduce ICH-induced brain injury and promote the recovery outcome in ICH patients are available to improve the recovery from ICH. Given that aquaporin 9 (AQP9) plays a critical role in brain edema after ischemic stroke and traumatic brain injury and is involved in the regulation of angiogenesis, we examined the role of AQP9 in preventing neuronal loss and in neovascularization in the dorsal hippocampus (DH) after ICH. We found that intra-DH collagenase-induced ICH increased AQP9 protein levels in the hippocampus, which was associated with behavioral deficits in wild-type mice. However, ICH robustly enhanced behavioral deficits in the AQP9-null mice, as compared with the wild-type mice. Furthermore, neovascularization and proliferation of brain microvascular endothelial cells following ICH were severely impaired in the AQP9-null mice, as compared with the wild-type mice. Finally, hippocampal neuronal loss following ICH became severer in the AQP9-null mice, relative to the wild-type mice. Taken together, our findings indicated that AQP9 in the brain may play a compensatory role in response to ICH, promote brain angiogenesis, and prevent subsequent neuronal death, thus preventing the deterioration of neurological outcome of ICH.

Risk of intracranial hemorrhage associated with therapeutic anticoagulation for venous thromboembolism in cancer patients: a systematic review and meta-analysis.

Intracranial hemorrhage (ICH) in cancer patients can result from tumor bleeding and from antitumor and anticoagulation therapy. The effect of anticoagulation on the incidence of ICH in cancer patients has not been quantified. Our objective was to determine the risk of intracranial hemorrhage associated with anticoagulation therapy for cancer-associated venous thromboembolism (VTE). Systematic review and meta-analysis of studies assessing the safety of anticoagulation therapy in patients with cancer-associated VTE. The primary endpoint of interest was the incidence of ICH and secondary outcomes included all major bleeding, and the time to ICH and major bleeding. After identifying 595 studies, five studies and 2089 patients were included in the analyses. We found that the relative risk (RR) for ICH was 0.494, 95 % CI (0.105-2.331) when low molecular weight heparin (LMWH) with vitamin K antagonist (VKA) anticoagulants were compared. No statistically significant differences in risk were measured. The risk of major bleeding using any type of anticoagulation therapy in patients with cancer-associated VTE was RR 0.853, 95 % CI (0.549, 1.327). After meta-analytic review of data published through August 2015, we conclude that therapeutic anticoagulation with LMWH given ≤6 months does not increase the risk of ICH in cancer patients compared to VKA. The risk of ICH in cancer patients is also similar to that of non-cancer patients. Available data were insufficient to determine if the ICH risk increase changes when the duration of anticoagulation is >6 months.

Clinical course of untreated cerebral cavernous malformations: a meta-analysis of individual patient data

SummaryBackgroundCerebral cavernous malformations (CCMs) can cause symptomatic intracranial haemorrhage (ICH), but the estimated risks are imprecise and predictors remain uncertain. We aimed to obtain precise estimates and predictors of the risk of ICH during untreated follow-up in an individual patient data meta-analysis.MethodsWe invited investigators of published cohorts of people aged at least 16 years, identified by a systematic review of Ovid MEDLINE and Embase from inception to April 30, 2015, to provide individual patient data on clinical course from CCM diagnosis until first CCM treatment or last available follow-up. We used survival analysis to estimate the 5-year risk of symptomatic ICH due to CCMs (primary outcome), multivariable Cox regression to identify baseline predictors of outcome, and random-effects models to pool estimates in a meta-analysis.FindingsAmong 1620 people in seven cohorts from six studies, 204 experienced ICH during 5197 person-years of follow-up (Kaplan-Meier estimated 5-year risk 15·8%, 95% CI 13·7–17·9). The primary outcome of ICH within 5 years of CCM diagnosis was associated with clinical presentation with ICH or new focal neurological deficit (FND) without brain imaging evidence of recent haemorrhage versus other modes of presentation (hazard ratio 5·6, 95% CI 3·2–9·7) and with brainstem CCM location versus other locations (4·4, 2·3–8·6), but age, sex, and CCM multiplicity did not add independent prognostic information. The 5-year estimated risk of ICH during untreated follow-up was 3·8% (95% CI 2·1–5·5) for 718 people with non-brainstem CCM presenting without ICH or FND, 8·0% (0·1–15·9) for 80 people with brainstem CCM presenting without ICH or FND, 18·4% (13·3–23·5) for 327 people with non-brainstem CCM presenting with ICH or FND, and 30·8% (26·3–35·2) for 495 people with brainstem CCM presenting with ICH or FND.InterpretationMode of clinical presentation and CCM location are independently associated with ICH within 5 years of CCM diagnosis. These findings can inform decisions about CCM treatment.FundingUK Medical Research Council, Chief Scientist Office of the Scottish Government, and UK Stroke Association.

Abstract 13573: Trends, Predictors and Outcomes of Intracranial Hemorrhage in Patients With Left Ventricular Assist Device

Introduction: Left ventricular assist device (LVAD) is being increasingly utilized in patients with advanced heart failure both as bridge to heart transplantation and as destination therapy. Intracranial hemorrhage (ICH) is one of major complications associated with LVAD. However, current trends on utilization of LVAD and associated ICH in real world practice are not known. Methods: We analyzed patients in the Nationwide Inpatient Sample (NIS) between 2007 and 2011. Heart failure patients with LVAD were identified from the database and patients with discharge diagnosis of ICH were compared to those without ICH. Trends and outcomes of ICH in patients with LVAD were analyzed. In addition, predictors of ICH were identified using a multivariate regression model. Results: We identified 20,443 discharges with a primary diagnosis of heart failure with LVAD of which 447 patients had a co-diagnosis of ICH. We saw a significant increase in discharge diagnosis of heart failure with LVAD from 1232 discharges in 2007 to 6308 in 2011 (p&lt0.001)(Figure). However, the incidence of ICH in this patient population decreased from 3.9% in 2007 to 2.4% in 2011. On multivariate analysis, in-hospital mortality was significantly higher in the ICH group (OR: 9.5, P=0.0001). After adjustment for potential confounders age &lt35 years (OR: 2.4, P=0.01) and a rising Charlson co-morbidity index score were independent predictors of ICH whereas presence of diabetes (OR: 0.05, P=0.001), chronic lung disease (OR:0.07, P=0.001), renal disease (OR: 0.09, P=0.001) and peripheral vascular disease (OR: 0.12, P=0.002) were found to be protective of ICH. Conclusions: Our analysis indicates an increasing trend in utilization of LVAD but a decrease in incidence of ICH over the same period. ICH was found to increase risk of mortality by nearly 10 fold. Increasing comorbidity burden increases the risk of ICH whereas age and certain individual co-morbidities appear to have a paradoxical effect on risk of ICH.

Abstract 17236: Intracranial Hemorrhage in Patients With Atrial Fibrillation in the ARISTOTLE Trial: Clinical Characteristics and Associated Outcomes

Background: Intracranial hemorrhage (ICH) is associated with poor outcomes in patients with atrial fibrillation (AF) treated with oral anticoagulation. Little is known about clinical characteristics and factors associated with ICH and subsequent outcomes in patients receiving apixaban. Methods: The ARISTOTLE trial randomized 18,201 patients with AF and risk of stroke to warfarin or apixaban. All ICH events were identified and adjudicated by a central committee blinded to the study treatment assignment. ICH events were analyzed in patients receiving at least one dose of study drug (N=18,140). Multivariable cox regression models were developed to identify factors associated with ICH. Results: There were 174 (1.0%) ICH events. Of those, 111 (67.7%) were intracerebral hemorrhage, 50 (30.7%) subdural hematomas, and 25 (15.3%) subarachnoid hemorrhage. Patients with ICH were older and had higher CHADS 2 score than patients without ICH. Computed tomography was used in 95.2% of patients for the diagnosis of ICH. The majority of ICH cases were spontaneous (71.7%) and 91.4% of patients with ICH presented with some type of neurological deficit. Most (72%) of the patients received conservative treatment and 21% underwent surgical intervention; 71 (40.8%) patients died in hospital. The mean modified Rankin score at discharge of survivors was ≥4 in 23 (22%) patients. Apixaban was superior to warfarin in causing less ICH, including as categorized by each ICH location. Factors associated with ICH were older age, warfarin randomized treatment assignment, prior stroke, geographic region of the world, and use of aspirin at randomization (Table). Conclusion: ICH is uncommon in patients with AF who are treated with oral anticoagulant and is associated with very high mortality. Apixaban is superior to warfarin in causing less ICH, irrespective of the location and other risk factors for ICH.

Racial and Ethnic Heterogeneity in Serum Lipid (SL) Prediction of Body Mass Index (BMI)

Whether nonintracranial hemorrhage (NICH) associated with intravenous thrombolysis (IVT) is a predictor of intracranial hemorrhage (ICH) and poor prognosis is ambiguous. We sought to analyze the rate of NICH and the relationship between NICH and poor outcome in the ischemic stroke population undergoing IVT.This is a single-center, hospital-based prospective study. All ischemic stroke patients undergoing IVT between December 2015 and November 2016 were included. NICH was defined according to the criteria of the Bleeding Academic Research Consortium (BARC). ICH associated with IVT was defined based on the European Cooperative Acute Stroke Study II definition. On the basis of the modified Rankin Scale (mRS), 90-day outcome was divided into favorable outcome (mRS score 0-1) versus unfavorable outcome (mRS score 2-6) and independency (mRS score 0-2) versus dependency and death (mRS score 3-6).A total of 212 patients undergoing IVT were included in the analysis. Forty-five NICH events were reported in 42 patients (19.8%). Older age was independently associated with NICH (P = .049, odds ratio [OR] = .97, 95% confidence interval [CI] .94-1.0). Neither NICH with BARC class 1 or higher (P = .56, OR = .61, 95% CI .11-3.24) nor NICH with BARC class 2 or higher (P = .87, OR = 1.19, 95% CI .14-10.23) was associated with ICH. NICH with BARC class 1 or higher was not associated with unfavorable outcome (P = .67, OR = 1.17, 95% CI .56-2.45) and dependence and death (P = .47, OR = .72, 95% CI .30-1.75), neither was NICH with BARC class 2 or higher (P = .97, OR = 1.02, 95% CI .46-2.27 and P = .30, OR = .59, 95% CI .22-1.62).NICH was common among ischemic stroke populations receiving IVT. NICH with BARC class 2 or lower was not associated with ICH and poor outcome.

Meta-analysis of intracranial hemorrhage in acute coronary syndromes: incidence, predictors, and clinical outcomes.

BackgroundLittle is known about the incidence, predictors, or outcomes of intracranial hemorrhage (ICH) in patients with non–ST-segment elevation acute coronary syndromes (NSTE ACS). We aimed to determine the incidence and timing of ICH, characterize the location of ICH, and identify independent baseline predictors of ICH in NSTE ACS patients.Methods and ResultsWe pooled patient-level data from 4 contemporary antithrombotic therapy trials. Multivariable modeling identified independent predictors of ICH. ICHs were adjudicated by a clinical events committee. Of 37 815 patients, 135 (0.4%) had an ICH. The median (25th, 75th percentiles) follow-up was 332 (184, 434) days but differed across trials. Locations of ICH were intracerebral (50%), subdural (31%), subarachnoid (18.5%), and intraventricular (11%). Independent predictors of ICH were older age (HR per 10 years, 1.61; 95% CI, 1.35 to 1.91); prior stroke/transient ischemic attack; HR, 1.95; 95% CI, 1.14 to 3.35), higher systolic blood pressure; HR per 10 mm Hg increase, 1.09; 95% CI, 1.01 to 1.18), and larger number of antithrombotic agents (HR per each additional agent, 2.06; 95% CI, 1.49 to 2.84). Of all ICHs, 45 (33%) were fatal.ConclusionsIn patients with NSTE ACS enrolled in recent clinical trials of antithrombotic therapies, ICH was uncommon. Patients with older age, prior transient ischemic attack/stroke, higher systolic blood pressure, or larger number of antithrombotic agents were at increased risk. One-third of patients with ICH died. These data may be useful to trialists and data and safety monitoring committees for trial conduct and monitoring.Clinical Trial RegistrationURL: https://www.clinicaltrials.gov/. Unique identifiers: TRACER: NCT00527943, PLATO: NCT00391872, APPRAISE-2: NCT00831441, TRILOGY ACS: NCT00699998.

Abstract 184: Clinical Outcomes According to Previous Intracranial Hemorrhage in Patients Receiving Intravenous Thrombolysis

Objective: This study aimed to describe clinical outcomes in patients treated with intravenous (IV) tPA according to evidence of previous Intracranial hemorrhage (ICH) and investigate the associations between previous ICH and clinical outcomes. Methods: Using a prospective multicenter stroke registry database, we identified acute ischemic stroke patients who were hospitalized to the 14 participating centers between January 2011 and July 2013 and were treated with IV tPA within 4.5 h of onset. Presence of previous ICH was screened using the formal radiologic reports or the clinical history of ICH from the registry database. If suspected, previous ICH was confirmed through direct review of brain MRI. As clinical outcomes, modified Rankin scale (mRS) 0-1 at discharge, mortality during hospitalization and symptomatic hemorrhagic transformation (sHT) were collected. sHT was defined according to the definition of SITS-MOST trial. Results: Among 1495 patients who were treated with IV tPA, 70 (4.7%) had evidence of previous ICH. sHT developed in 69 (4.6%) of all subjects; 7.1% (n=5) of 70 patients with previous ICH and 4.5% (n=64) of 1425 without previous ICH (p=0.25 on Fisher’s exact test). Hospital Mortality and mRS 0-1 at discharge was observed in 5.6% and 26.6% of all subjects and in 8.6% and 22.9% of those with previous ICH and 5.4% and 26.7% in those without it (p=0.28 on Fisher’s exact test and p=0.47 on Pearson’s chi-squared test, respectively). Multivariable logistic regression analysis with adjustment for age, initial National Institute of Health Stroke Scale, initial glucose and tPA dose showed that previous ICH was not associated with sHT, mortality during hospitalization and having discharge mRS 0-1 (p’s >0.4). Review of MRI on 5 patients who had previous ICH and developed sHT after IV tPA demonstrated that, in 4 cases, location of sHT was different from where previous ICH had developed, but in 1 case sHT occurred exactly where previous ICH had developed. Conclusions: This study shows that previous ICH may not increase the risk of sHT and death and aggravate functional outcome at discharge. However, it should be noted that the retrospective nature and small sample size of this study limit the generalization of its results.

Hybrid Assistive Limb (HAL) Rehabilitation in Patients with Acute Hemorrhagic Stroke.

The efficacy of hybrid assistive limb (HAL) rehabilitation in the acute phase of stroke remains unclear. The purpose of this study was to evaluate the outcomes of patients with acute intracranial hemorrhage (ICH) who were treated with or without HAL rehabilitation. Among 270 patients with acute ICH from 2009 to 2014, 91 patients with supratentorial ICH were included in this retrospective study. Of these, 14 patients (HAL group) received HAL rehabilitation at approximately 1 week after ICH occurrence, while the remaining 77 patients received usual rehabilitation without HAL (N-HAL group). We obtained various patient data from the hospitals where the patients were moved to for further rehabilitation. Statistical comparisons were performed for the characteristics of the ICH patients, and outcomes between the HAL and N-HAL groups. There were no differences in outcomes between the HAL and N-HAL groups. However, patients with right ICH in the HAL group exhibited a significant association with a functional independence measure (FIM) score of ≥ 110 compared with patients in the N-HAL group (HAL group: 81.8%, N-HAL group: 43.9%, P = 0.04). In patients with right ICH, HAL rehabilitation was associated with improved outcomes as evaluated by the FIM score. Thus, HAL rehabilitation may improve outcomes of acute ICH in appropriately selected patients.

Incidence of Intracranial Hemorrhage and Outcomes after Ground-level Falls in Geriatric Trauma Patients Taking Preinjury Anticoagulants and Antiplatelet Agents

Antiplatelet and anticoagulant medication increases the risk of intracranial hemorrhage (ICH) after a fall in geriatric patients. We sought to determine whether there were differences in ICH rates and outcomes based on type of anticoagulant or antiplatelet agent after a ground-level fall (GLF). Our institutional trauma registry was used to identify patients 65 years old or older after a GLF while taking warfarin, clopidogrel, or aspirin over a 2-year period. Rates and types of ICH and patient outcomes were evaluated. Of 562 patients who met inclusion and exclusion criteria, 218 (38.8%) were on warfarin, 95 (16.9%) were on clopidogrel, and 249 (44.3%) were on aspirin. Overall ICH frequency was 15 per cent with no difference in ICH rate, type of ICH, need for craniotomy, mortality, or intensive care unit or hospital length of stay between groups. Patients with ICH were more likely to present with abnormal Glasgow Coma Score, history of hypertension, and/or loss of consciousness.

Effect of warfarin on intracranial hemorrhage incidence and fatal outcomes

Avoiding intracranial hemorrhage (ICH) during warfarin therapy is critical but little is known about factors that affect warfarin-related ICH outcomes. We aimed to define the impact of warfarin on ICH incidence rates and to identify baseline clinical characteristics of patients who experienced ICH and factors associated with fatal ICH. The primary outcome of this retrospective cohort study was the incident ICH rate per 10,000 person-years for patients receiving and not receiving warfarin therapy. Cox proportional hazards modeling was used to adjust for potential confounding factors in assessment of the association of warfarin with fatal ICH. A total of 1348 patients with incident ICH, 259 (19%) who were receiving warfarin therapy, were included. The incident ICH rates were 74/10,000 (warfarin) and 5/10,000 (non-warfarin) person-years (p<0.001). Warfarin patients were older and carried a higher burden of chronic disease. The unadjusted hazard ratio (HR) for fatal ICH was 1.64 (95% confidence interval [CI] 1.31-2.05) for warfarin patients compared to non-warfarin patients. However, the HR was no longer significant after adjustment for confounding variables (1.10; 95% CI 0.84-1.42). An INR greater than 3.5 at presentation doubled the adjusted risk for fatal ICH with warfarin therapy. Subarachnoid and subdural ICHs were less likely to be fatal than other ICH types, and each year increase in age was associated with 4% increased risk of fatal ICH. Although warfarin use increases the rate of incident ICH, other factors impact the risk of fatal ICH, even among anticoagulated patients.

Multiple factors related with intracranial hemorrhage of dural arteriovenous fistula: clinical analysis

To discuss the relevant predicative factors of dural arteriovenous fistula (dAVF) in intracranial hemorrhage. A total of 144 consecutive patients with dAVFs were recruited for a retrospective analysis from 1996 to 2006. The relevant factors of gender, age, fistula flow rate, arterial supply, lesion and venous drainage pattern were analyzed to evaluate the outcome of intracranial hemorrhage. Univariate analysis showed that gender, lesion and venous drainage pattern were statistical significant for intracranial hemorrhage of DAVF (P < 0.05). However, only venous drainage pattern was significant in the predication of intracranial hemorrhage (P < 0.05). Only venous drainage pattern is significant in the predication of dural arteriovenous fistulas in intracranial hemorrhage. Both gender and lesion may be confounding factors.

Diagnosis and treatment of intracranial hemorrhage in children with hemophilia

Intracranial hemorrhage (ICH) is a significant complication for children with hemophilia. Identifying risk factors may allow us to establish clinically relevant guidelines for the diagnosis and management of ICH. The purpose of this review is to nucleate evidence from the available literature on the incidence, risk factors, presentation, treatment, and outcomes of ICH that can be utilized to develop a clinically useful framework for the diagnosis and management of hemophiliac patients with the condition. An electronic MEDLINE and EMBASE literature search was undertaken using the key words 'intracranial hemorrhage and hemophilia' and setting limits as: Last 10 years and Review or Randomized Controlled Trial (RCT) or Clinical Trial, or Practice Guidelines. Following review of all articles using predetermined search words and criteria, 31 were retrieved with sufficient data to address our objectives. An algorithm is presented for the management of children (≥3 years-18 years) with hemophilia and suspected ICH. A standardized approach to ICH may reduce unnecessary exposure to radiation via computed tomography scan in a select group of children. Currently there is limited scientific evidence to recommend a diagnostic and therapeutic algorithm for neonates with hemophilia.

Fetal intracranial haemorrhages caused by fetal and neonatal alloimmune thrombocytopenia: an observational cohort study of 43 cases from an international multicentre registry

ObjectiveTo characterise pregnancies where the fetus or neonate was diagnosed with fetal and neonatal alloimmune thrombocytopenia (FNAIT) and suffered from intracranial haemorrhage (ICH), with special focus on time of bleeding...

Intracranial hemorrhage in adult patients with hematological malignancies

BackgroundClinical characteristics and outcomes of intracranial hemorrhage (ICH) among adult patients with various hematological malignancies are limited.MethodsA total of 2,574 adult patients diagnosed with hematological malignancies admitted to a single university hospital were enrolled into this study between 2001 and 2010. The clinical characteristics, image reports and outcomes were retrospectively analyzed.ResultsA total of 72 patients (48 men and 24 women) with a median age of 56 (range 18 to 86) had an ICH. The overall ICH incidence was 2.8% among adult patients with hematological malignancies. The incidence of ICH was higher in acute myeloid leukemia (AML) patients than in patients with other hematological malignancies (6.3% vs 1.1%, P = 0.001). ICH was more common among patients with central nervous system (CNS) involvement of lymphoma than among patients with CNS involved acute leukemia (P <0.001). Sites of ICH occurrence included the cerebral cortex (60 patients, 83%), basal ganglia (13 patients, 18%), cerebellum (10 patients, 14%), and brainstem (5 patients, 7%). A total of 33 patients (46%) had multifocal hemorrhages. In all, 56 patients (77%) had intraparenchymal hemorrhage, 22 patients (31%) had subdural hemorrhage, 15 patients (21%) had subarachnoid hemorrhage (SAH), and 3 patients (4%) had epidural hemorrhage. A total of 22 patients had 2 or more types of ICH. In all, 46 (64%) patients died of ICH within 30 days of diagnosis, irrespective of the type of hematological malignancy. Multivariate analysis revealed three independent prognostic factors: prolonged prothrombin time (P = 0.008), SAH (P = 0.021), and multifocal cerebral hemorrhage (P = 0.026).ConclusionsThe incidence of ICH in patients with AML is higher than patients with other hematological malignancies. But in those with intracranial malignant disease, patients with CNS involved lymphoma were more prone to ICH than patients with CNS involved acute leukemia. Mortality was similar regardless of the type of hematological malignancy. Neuroimaging studies of the location and type of ICH could assist with prognosis prediction for patients with hematological malignancies.

Intracranial Hemorrhage Associated With Vitamin K–deficiency Bleeding in Patients With Biliary Atresia

The prophylactic oral administration of vitamin K to newborns has markedly reduced the incidence of vitamin K deficiency (VKD); however, intracranial hemorrhage (ICH) is still one of the complications found in biliary atresia (BA) patients and is associated with VKD bleeding. Therefore, we aimed to investigate the incidence and long-term outcome of ICH in patients with BA who previously received prophylactic vitamin K during the neonatal period. Eighty-eight consecutive infants with BA were treated and followed up at Kyushu University Hospital from 1979 to 2009. The clinical records and imaging study results were retrospectively reviewed in the infants with BA who presented with ICH. ICH occurred in 7.95% of patients with BA. The onset of ICH occurred at 47 to 76 days after birth, before the patients underwent surgery for BA (9-37 days after the onset of ICH). Coagulopathy was found upon admission in all of the cases with available data and improved after intravenous administration of vitamin K. A craniotomy was required in 2 cases before the surgery for BA. During the 22 to 278 months of follow-up, some neurologic sequelae persisted in 5 of 7 cases. Follow-up head computed tomography scans showed a low-density area in the left hemisphere in 5 cases. Although vitamin K prophylaxis had been given during the neonatal period, ICH-associated VKD bleeding was still found in 7.95% of patients with BA. Persistent neurologic sequelae were found in 5 of 7 cases, with low-density area in the left hemisphere.

Surgical evacuation of neonatal intracranial hemorrhage due to vitamin K deficiency bleeding

Although the incidence of vitamin K deficiency bleeding (VKDB) in neonates has dramatically decreased in the developed world since the adoption of routine vitamin K prophylaxis, in developing countries the incidence is still high. Intracranial hemorrhage (ICH) is the most dangerous complication. Early recognition and management are important to decrease the mortality rate and neurological sequelae. The authors conducted a prospective study between January 2008 and June 2010. They included all full-term neonates referred to the Department of Neurosurgery at Mansoura University Children's Hospital with ICH complicating VKDB and necessitating surgical evacuation. The objective was to evaluate the clinical presentation, diagnosis, hospital course, and outcome of ICH in full-term neonates with VKDB after surgical evacuation. Thirty-two neonates with ICH due to VKDB were included. Diagnosis and classification of ICH were based on detailed history, physical examination, and the interpretation of CT or MR imaging studies. The diagnosis of VKDB was based on pretreatment coagulation studies (prothrombin time [PT] and partial thromboplastin time [PTT]), which are grossly abnormal, together with a normal platelet count and correction of coagulation results to normal after vitamin K administration. The mean age (± SD) at onset of symptoms was 20.4 ± 4.9 days. Two neonates (6.25%) had early VKDB, 7 (21.9%) had classic VKDB, and 23 (71.9%) had late VKDB. The most common neurological manifestations included focal seizures, disturbed consciousness level, and tense anterior fontanel. The most common general manifestations included pallor, respiratory distress, and bleeding from other sites. Radiological findings varied from acute subdural hemorrhage (SDH) in 18 cases (56.3%), intracerebral hemorrhage in 10 (31.3%), and acute SDH with underlying intracerebral hemorrhage, intraventricular hemorrhage, and/or subarachnoid hemorrhage in 4 (12.5%). Before administration of vitamin K, the PT was 72.1 ± 45.0 seconds and the PTT was 112.4 ± 57.6 seconds. Six to 12 hours after administration of vitamin K, the PT was 14.6 ± 1.6 seconds and the PTT was 34.4 ± 1.0 seconds. All patients underwent surgery for evacuation of the ICH after correction of PT, prothrombin activity, and international normalized ratio. Evacuation of the ICH was done by either free or osteoblastic bone flap. Six patients (18.8%) died, and the other 26 patients had variable degrees of morbidity during the follow-up period (3-24 months). Vitamin K deficiency bleeding, especially the late-onset form, is an important cause of neonatal ICH. In the present study, the most frequent form of ICH in neonates was SDH. Focal seizures, disturbed consciousness level, tense anterior fontanel, unexplained anemia, and respiratory distress were the major presenting signs. Despite early surgical evacuation, these cases are associated with high mortality rate and neurological disabilities. Vitamin K prophylaxis at birth may reduce these severe complications.

Clinical Manifestations of Symptomatic Intracranial Hemorrhage in Term Neonates: 18 Years of Experience in a Medical Center

Intracranial hemorrhage (ICH) is an uncommon but important cause of morbidity and mortality in term neonates. We conducted a retrospective analysis of the clinical characteristics and developmental outcomes of symptomatic ICH in term neonates. A retrospective chart review was conducted of all term neonates (less than 1 month old) diagnosed with ICH and admitted to the neonatal intensive care unit of Kaohsiung Chang Gung Hospital from December 1991 to December 2008. Demographic characteristics, mode of delivery, laboratory data, clinical presentation, and developmental status were recorded. Data for 24 term neonates (17 boys and 7 girls) with a diagnosis of ICH were collected for analysis. The clinical manifestations of ICH included anemia (13/24, 54%), seizure (11/24, 46%), cyanosis (7/24, 29%), tachypnea (5/24, 21%), fever (1/24, 4%), hypothermia (1/24, 4%), and poor feeding (1/24, 4%). Age at symptom onset ranged from 2 hours to 11 days following birth. The most common type of ICH was subdural hemorrhage. All ICHs resolved, except in one infant, who died from hypoxicischemic encephalopathy at 25 days. Ten children with symptomatic ICH were reported to have normal development, while the remainder (13/23, 57%) showed developmental delays or disabilities. Unexplained anemia, seizure, and cyanosis were the major presenting signs in infants with symptomatic ICH. A diagnosis of ICH should be considered in term neonates who present with one or more of these signs. Although the mortality in term infants with symptomatic ICH was low, more than half.

Intracranial Haemorrhage in Patients with An Inherited Bleeding Disorder: A Review of 10 Years Experience in a UK Haemophilia Comprehensive Centre.

Abstract 3489Poster Board III-426 Introduction-Inherited bleeding disorders comprise a heterogeneous group of diseases that reflect abnormalities of coagulation proteins, platelets and blood vessels. Intracranial haemorrhage (ICH) is an unusual but life-threatening complication of such disorders. A 10-year retrospective study was conducted to investigate the episodes of ICH in patients with an inherited bleeding disorder who where followed by a regional haemophilia comprehensive care center in the UK. Methods-All cases of ICH occurring in patients with an inherited bleeding disorder which presented between 1999 and 2009 were retrospectively identified using the haemophilia centre database. Case notes were reviewed and aetiology, clinical features, radiological findings, management and outcome of ICH in this population were studied. Results-Of 640 patients registered with an inherited bleeding disorder in haemophilia centre database, a total of 10 ICHs in 9 patients were identified. Age of patients ranged from 5 months to 72 years with a higher number of males (M:F = 7:2). Diagnosis included: Severe haemophilia A (3 patients); Mild haemophilia A (1 patient); Severe haemophilia B (1 patient); Type 2A von Willebrand disease (VWD) (1 patient); Type 3 VWD (1 patient); Congenital afibrinogenemia (1 patient); Severe factor V deficiency (1 patient). Two of the patients with severe haemophilia A had inhibitors, one of whom was receiving immune tolerance therapy at the time of the ICH. 7 of ICHs were spontaneous and 3 were trauma-related. ICH was the first significant bleeding event in 2 patients- one with severe haemophilia A, aged 5 months, and one with severe haemophilia B, aged 6 months. Type of ICHs were 7 subdural, 1 subarachnoid and 2 subdural with intracerebral. All patients were symptomatic. Common presenting features were headache (6 patients), vomiting (5 patients), limb paralysis (3 patients), cranial nerve palsy (3 patients) and seizures (2 patients). None had systemic bleeding concurrent to the ICH. Initial diagnostic modality was CT scan without contrast for all patients. The two patients with severe haemophilia A and inhibitors were initially treated with recombinant factor VIIa. The remaining patients with haemophilia were treated with factor VIII/IX concentrate. The patient with severe haemophilia B required surgical evacuation. The patients with severe haemophilia A/B without inhibitors were commenced on long-term prophylaxis with factor replacement therapy following their ICH. The patient with congenital afibrinogenemia was initially treated with fibrinogen concentrate, repeated CT scan on day ten showed significant expansion of hematoma, surgical evacuation was done and he was commenced on long-term prophylaxis. The patient with factor V deficiency received prothrombin complex concentrate (octaplex). The two patients with VWD were treated with haemate P, the patient with type 2A VWD received prophylaxis for 4 weeks. The patient with type 3 VWD died within an hour of admission despite haemate P treatment. Six patients had long-term morbidity including limb weakness, seizure, ventriculoperitoneal shunt and developmental delay. These results are summarized in Table 1. Conclusions-ICH can occur in patients with a severe inherited bleeding disorder and can result in substantial morbidity and mortality. ICH can also occur in patients with a mild inherited bleeding disorder following trauma. There is no reliable predictor for intracranial bleeding which could aid decision-making in terms of prophylactic therapy to prevent ICH. CT scan is an appropriate initial diagnostic modality. It is important to educate patients and parents about symptoms to allow early diagnosis. Treatment should be administered rapidly to control bleeding in order to limit adverse outcomes.Table 1AgeSexDiagnosisType of ICHSpontaneous or traumaticLong term morbidity/mortality5MoMSevere Haemophilia ASDHSpontaneousDevelopmental delay, VP shunt3YMSevere Haemophilia ASAHSpontaneousLimb weakness48YMSevere Haemophilia ASDHSpontaneousSeizure20YMMild Haemophilia ASDH and IntracerebralTraumaticNil6MoMSevere Haemophilia BSDHSpontaneousDevelopmental delay, Seizure, VP shunt37YMCongenital afibrinogenemiaSDHSpontaneousLimb weakness72YMType 2A VWDSDH and IntracerebralSpontaneousNil19YFType 3 VWDSDHTraumaticDied53 YFSevere factor V deficiencySDHTraumaticLimb weakness Disclosures:No relevant conflicts of interest to declare.

Treatment and Outcome of Intracranial Hemorrhage after Carotid Artery Stenting

Intracranial hemorrhage following carotid artery stenting (CAS) is a rare but potentially devastating complication. The present study reviewed intracranial hemorrhage cases from patients undergoing CAS in ten years to find the methods to rescue patients from this fatal complication. Patients with postoperative intracranial hemorrhage following CAS were retrospectively selected, and clinical features, treatments and outcomes were studied. Ten patients with intracranial hemorrhage were identified. The mean onset time of hemorrhage was 6.1-/+7.1h. Intracerebral hemorrhage occurred in eight patients and SAH in two patients. The patients were treated by stopping anti-platelet and anticoagulant for at least three days, and surgical drainage of the hematoma/ventricle drainage or conservative treatment. Six patients survived, two had left moderate paralysis, four had a good recovery at four week follow-up, and four patients died. No patients underwent thrombosis in stent after withdrawing of antiplatelet and anticoagulant. Intracranial hemorrhage after CAS occurs usually in a few hours and leads to catastrophic results. Once patients have intracranial hemorrhage, good neurocritical care may help to save them. Stopping antiplatelet and anticoagulant for at least three days may avoid thrombosis in the stenting site.