Cases Of Intracranial Hemorrhage Research Articles

Thrombolysis for acute stroke in patients with vasculitis: Case report and literature discussion

1. IntroductionTreatment with tissue plasminogen activator (tPA) is standardof care treatment of acute ischemic stroke. Various risk factorshave been associated with the development of intracranial hem-orrhage (ICH) following thrombolysis, but there is no literature onthe useoftPAinpatientswithknownvasculitiswhodevelopacuteischemic stroke. We present a case of ICH after tPA administrationin apatientwithknownChurg–StraussSyndrome(CSS)anddiscussthe implications of thrombolysis in patients with vasculitis.2. Case reportA 53-year old right-handed man with a past medical history ofwell controlled hyperlipidemia, negative anti-neutrophil cytoplas-mic antibodies (ANCA) CSS characterized by asthma, eosinophilia,nail-fold infarcts and peripheral neuropathy presented acutelywith dysarthria, left facial weakness and partial sensory loss overthe left upper extremity. CSS was diagnosed eleven years ear-lier based on the clinical presentation and with a skin biopsythat demonstrated vasculitis. There was no history of hyperten-sion or diabetes. His disease has not been well controlled since

Intracranial Hemorrhage as a Complication of Dobutamine Stress Echocardiography: Case Report and Review of the Literature

Dobutamine stress echocardiography is a generally well-tolerated study to evaluate patients with suspected coronary artery disease. Rare but life-threatening complications of this study have been well described. Severe hypertensive responses are a known but uncommon adverse reaction to dobutamine infusion. The authors report a case of intracranial hemorrhage in the setting of severe hypertension as a complication of dobutamine stress echocardiography. The patient was on systemic anticoagulation with warfarin for a prosthetic mitral valve and had an international normalized ratio (INR) of 3.8 that was slightly over the therapeutic goal INR of 2.5-3.5. He had no predisposing intracranial lesions such as tumor, vascular malformation, or aneurysm. He suffered an intraparenchymal hemorrhage in three distinct areas of his brain. Intracranial hemorrhage related to dobutamine infusion has not been reported previously, but given the known risk of hypertension, life-threatening sequelae including intracranial hemorrhage are possible.

MOde of delivery in women with inherited bleeding disorders

Women with inherited bleeding disorders (IBD) and their infants are at risk of bleeding complications at the time of childbirth. The aim of this study was to report mode of...

The Utility of Near Infrared Spectroscopy in Detecting Intracranial Hemorrhage in Children

A prospective case-control study was conducted in a tertiary care pediatric intensive care unit (PICU) to evaluate the use of near infrared spectroscopy (NIRS) for the detection of intracranial hemorrhage (ICH) in children. Subjects 0-14 years of age who had a computed tomography (CT) scan of the head performed as part of clinical care were eligible for enrollment. The children were stratified into two groups based on whether the CT was normal or abnormal. Children in the abnormal imaging cohort were further divided into those with ICH and those with other abnormalities of the brain parenchyma (contusions, diffuse axonal injury [DAI], or cerebral edema) or fractures. NIRS measurements were performed on all subjects within 24 h of head CT. The NIRS operator was blinded to the presence or absence of ICH. NIRS measurements were performed in eight different scalp locations (four bilaterally). A total of 103 measurements were made. The optical density (OD) was automatically calculated by comparing the reflected and diffused optical signal. A ΔOD>0.2 between hemispheres in any scalp location was considered abnormal. NIRS was performed in a total of 28 subjects: 7 had normal imaging and 21 had abnormal imaging. Of those with abnormal imaging, 12 had ICH. The sensitivity and specificity of NIRS at detecting ICH was 1.0 and 0.8, respectively. The positive and negative predictive values were 0.8 and 1.0, respectively. In conclusion, NIRS correctly identified all cases of ICH in this pilot study. Our preliminary results suggest that NIRS may be beneficial in the evaluation of a child with possible ICH.

Intracranial Hemorrhage Is Much More Common After Carotid Stenting Than After Endarterectomy

Intracranial hemorrhage (ICH) is a rare and devastating complication of carotid revascularization. We sought to determine the prevalence of, type of, and risk factors associated with ICH among recipients of carotid endarterectomy (CEA) and carotid angioplasty and stenting (CAS) within the National Inpatient Sample (NIS). Postoperative cases of ICH after CEA (International Classification of Disease 9th edition [ICD-9]: 38.12) or CAS (ICD-9: 00.63) were retrieved from the 2001 to 2008 NIS. Clinical presentation (asymptomatic versus symptomatic), discharge status, in-hospital mortality, demographics, and hospital characteristics were extracted from NIS data. Charlson indices of comorbidity were determined based on ICD-9 and clinical classification software codes. Multivariate regression was used to determine the impact of revascularization procedure type and symptom status on adverse outcomes, including ICH, in-hospital mortality, and unfavorable discharge status. Among 57,663,486 NIS hospital admissions, 215,012 CEA and 13,884 CAS procedures were performed. Symptomatic presentations represented the minority of CEA (N=10,049; 5%) and CAS cases (N=1251; 10%). ICH occurred significantly more frequently after CAS than CEA in both symptomatic (4.4% versus 0.8%; P<0.0001) and asymptomatic presentations (0.5% versus 0.06%; P<0.0001). Multivariate regression suggested that symptomatic presentations (versus asymptomatic) and CAS procedures (versus CEA) were both independently predictive of 6-fold to 7-fold increases in the frequency of postoperative ICH. ICH was independently predictive in a 30-fold increased risk of mortality before discharge. CAS procedures are associated with elevated adverse outcomes, including ICH, in-hospital death, and unfavorable discharges, especially among symptomatic presentations.

Phase II Study of Sunitinib in Patients with Non-small Cell Lung Cancer and Irradiated Brain Metastases

Brain metastases frequently cause significant morbidity in patients with non-small cell lung cancer (NSCLC). Sunitinib is a multitargeted inhibitor of tyrosine kinase receptors, including vascular endothelial growth factor receptors and platelet-derived growth factor receptors, which has single-agent antitumor activity in refractory NSCLC. This phase II study evaluated the antitumor activity and safety of sunitinib in patients with pretreated NSCLC and irradiated brain metastases. Patients received sunitinib 37.5 mg on a continuous daily dosing schedule. The primary end point was progression-free survival. Secondary end points included overall survival, patient-reported outcomes, and safety, including risk of intracranial hemorrhage (ICH) associated with focal neurological deficit. Sixty-four patients received sunitinib (median age 61 years), most (83%) had received prior systemic therapy, 63% had adenocarcinoma, and 19% had squamous cell carcinoma; most (55%) were never-smokers. Median progression-free survival was 9.4 weeks (90% confidence interval [CI]: 7.5-13.1), and median overall survival was 25.1 weeks (95% CI: 13.4-35.5). The most common treatment-emergent (all-causality) nonhematologic toxicities (any grade) were fatigue (38%) and decreased appetite and constipation (both 25%). The most common grade 3/4 nonhematologic toxicities were dyspnea (9%) and fatigue (8%). Lymphopenia (20%) and neutropenia (13%) were the most common grade 3/4 hematologic abnormalities. Serious neurologic adverse events occurred in six patients (9%), and none were treatment-related. No cases of ICH were reported. Sunitinib administration on a continuous daily dosing schedule in patients with NSCLC and brain metastases was safe and manageable, with no increased risk of ICH.

Cerebral Venous Sinus Thrombosis Associated With Cerebral Hemorrhage

The current recommended treatment for cerebral venous sinus thrombosis (CVST) is anticoagulation, and the presence of intracranial hemorrhage (ICH) is not a contraindication. We present a case of ICH associated with CVST in which heparin treatment was associated with rebleeding, and we review current evidence of anticoagulation safety in patients with ICH associated with CVST. A 65-year-old man presented with right hemiparesis and loss of consciousness. Brain computed tomography showed a left frontoparietal hemorrhage. Angiographic studies with magnetic resonance imaging showed the presence of a partial superior saggital sinus thrombosis. With a diagnosis of CVST, intravenous heparin was administered. After 24 hours the patient had a symptomatic increase in ICH size, and 2 days later the patient developed a status epilepticus with new evidence of rebleeding. Anticoagulant treatment was stopped and the patient experienced neurological improvement, with no new episodes of rebleeding. Evidence for the safety of anticoagulants in CVST comes from 2 small trials involving a total of 79 patients, but only 18 had some degree of bleeding in baseline computed tomography. A meta-analysis suggested that in CVST patients who are treated with anticoagulants, the risk of ICH is low, but acknowledged that an impact of up to 9% of new ICH cannot be ruled out. As there is not enough evidence for the safety of anticoagulant therapy in patients with early ICH associated with CVST, the therapeutic decision must be individualized and the rebleeding risk should be weighed in those patients.

Determinants of intracranial hemorrhage incidence in patients on oral anticoagulation followed at the Lahey clinic

Oral anticoagulation with warfarin is widely used to treat venous and arterial thromboembolic disease (Ansell et al. Chest 133(6 suppl):160S-198S, 2008). Its administration is associated with a risk of intracranial hemorrhage (ICH), a devastating complication which usually results in death or severe disability (Fang et al. Am J Med,120(8):700-705, 2007; Rosand et al. Arch Intern Med, 164(8):880-884, 2004). The international normalized ratio (INR) is one of the factors which can help determine the risk of ICH in a given individual (Singer et al. Circ Cardiovasc Qual Outcomes, 2(4):297-304, 2009). Using the DoseResponse(®) patient database at our institution, we carried a retrospective nested matched case-control study to identify patient characteristics associated with the occurrence of ICH. The database was queried for the years 2004-2009. Each case was matched by month to four control patients having a routine INR determination for the monitoring of chronic anticoagulation. The following characteristics were captured: bleeding type, INR, age, sex, blood pressure, hemoglobin, creatinine, presence or history of pertinent comorbid conditions, intake of antiplatelet agents (aspirin or thienopyridine) and indication for anticoagulation. The relationship between those risk factors and the odds ratio of ICH was determined with conditional logistic regression. Fifty cases of ICH were retrieved. When correcting for pertinent variables, the odds ratio of ICH increased significantly for higher INR values, with a quadratic relationship noted in the model. Increasing mean blood pressure seemed to be associated with a higher risk of ICH, also in an exponential manner. Rising hemoglobin values on the other hand seemed to have a protective effect against such events. About 50% of cases of ICH occurred in or below the therapeutic INR range. The intake of antiplatelet agent was found to be associated with ICH in univariate analysis only. The INR is an important predictor for the incidence of ICH, but in this study an elevated measurement was found in only half of cases. Mean blood pressure appears to be another important determinant of the risk of ICH in the anticoagulated patient population.

TROPICS 1: A Phase III, Randomized, Double-blind, Placebo-controlled Study of Tenecteplase for Restoration of Function in Dysfunctional Central Venous Catheters

To evaluate the efficacy and safety of the thrombolytic tenecteplase, a fibrin-specific recombinant tissue plasminogen activator, for restoring function to dysfunctional central venous catheters (CVCs). In this double-blind, placebo-controlled study, eligible patients with dysfunctional nonhemodialysis CVCs were randomly assigned to two treatment arms. In the first arm (TNK-TNK-PBO), patients received an initial dose of intraluminal tenecteplase (TNK) (up to 2 mg), a second dose of tenecteplase if indicated, and a third placebo (PBO) dose. In the PBO-TNK-TNK arm, placebo was instilled first followed by up to two doses of tenecteplase, if needed, for restoration of catheter function. After administration of each dose, CVC function was assessed at 15, 30, and 120 minutes. There were 97 patients who received either TNK-TNK-PBO (n = 50) or PBO-TNK-TNK (n = 47). Within 120 minutes of initial study drug instillation, catheter function was restored to 30 patients (60%) in the TNK-TNK-PBO arm and 11 patients (23%) in the PBO-TNK-TNK arm, for a treatment difference of 37 percentage points (95% confidence interval 18-55; P = .0002). Cumulative restoration rates for CVC function increased to 87% after the second dose of tenecteplase in both study arms combined. Two patients developed a deep vein thrombosis (DVT) after exposure to tenecteplase; one DVT was considered to be drug related. No cases of intracranial hemorrhage, major bleeding, embolic events, catheter-related bloodstream infections, or catheter-related complications were reported. Tenecteplase was efficacious for restoration of catheter function in these study patients with dysfunctional CVCs.

Determinants of Intracranial Hemorrhage Incidence in Patients on Oral Anticoagulation Followed at the Lahey Clinic.

AbstractAbstract 1101 Background:oral anticoagulation with warfarin is used to treat venous and arterial thromboembolic disease. Its administration is associated with a risk of intracranial hemorrhage (ICH), a devastating complication which usually results in death or severe disability. The international normalized ratio (INR) is one of the factors which can help determine the risk of ICH in a given individual (Singer DE et al, Circ Cardiovasc Qual Outcomes 2009). Materials and methods:using the DoseResponse® patient database at our institution, we carried out a retrospective nested matched case-control study to identify patient characteristics associated with the occurrence of ICH. The database was queried for the years 2007 to 2009. Each case was matched by month to 4 control patients having a routine INR determination for the monitoring of chronic anticoagulation. The following characteristics were captured: INR, age, sex, systolic and diastolic blood pressure, hemoglobin, creatinine, history of pertinent medical conditions (hypertension, diabetes, heart failure, gastrointestinal bleeding, ischemic stroke, active cancer, substance abuse, cirrhosis), indication for anticoagulation (non-valvular atrial fibrillation, valvular atrial fibrillation, venous thromboembolism or other) and intake of antiplatelet agent. Blood pressure for cases was obtained from a medical encounter occurring before the bleeding event. The relationship between those risk factors and the odds ratio of ICH was determined with conditional logistic regression, using the SAS® 9.2 software platform. The initial approach consisted of stepwise regression with forward selection and backward elimination. Results:31 cases of ICH were retrieved; they were matched to 124 controls. In the univariate analysis, the two groups differed significantly only in terms of their hemoglobin: 12.8 versus 13.5 g/dL for cases and controls, respectively (p=0.048). As for the INR, the mean value was 3.0 for cases vs 2.5 for controls. The distribution of this parameter was normal albeit more markedly skewed to the right for cases, with 3 values of 5.0 or more, compared to only one instance of this for controls. Most cases of ICH occurred in the setting of a therapeutic INR. The odds ratio (OR) of ICH (using the interval 2.01 to 2.50 as the reference) started increasing above an INR of 3.50, reaching its highest level in individuals with an INR value greater than 4.50 (OR=5.78, 95% CI=1.10-30.48). Mean blood pressures were similar between the two groups: 92 vs 89 mmHg for cases vs controls, respectively (p=0.252). The variables retained in the final regression model on the basis of statistical significance and clinical pertinence are shown in the table. The OR of ICH was 1.50 for increments of 1.0 in INR value (p=0.021), while it was 1.56 for increments of 10 mmHg in mean blood pressure (p=0.032). The presence of cancer, anemia and heart failure appeared to contribute to the risk of an event but the associations for those factors were not statistically significant. Conclusion:the INR is an important predictor for the incidence of ICH, but a supratherapeutic measurement is found only in a minority of cases; the risk of an event increases markedly with an INR above 3.5. Mean blood pressure is another important determinant of the risk of ICH in individuals on chronic warfarin therapy. Previous studies have shown that a diagnosis of hypertension is associated with an increased risk of ICH in the anticoagulated patient population (Berwaerts J et al, QJM 2000; Atrial Fibrillation Investigators, Arch Intern Med 1994; Singer DE et al, Ann Intern Med 2009), but to the knowledge of this author there has been no report describing the variation in this risk over the spectrum of mean blood pressures. This lends support to the generally accepted practice of aggressively treating arterial hypertension in patients on chronic oral anticoagulation.Multivariable AnalysisParameterOdds Ratio95% Confidence IntervalpINR (increase of 1.0)1.5001.062–2.1170.021Mean blood pressure (increase of 1 mmHg)1.0451.004–1.0890.032Age (increase of 1 year)1.0000.964–1.0370.984Use of antiplatelet drug0.9860.387–2.5140.977Substance abuse0.6370.070–5.8110.689Ischemic stroke1.0620.306–3.6890.925Indication for anticoagulation is “other”0.2710.030–2.4210.243Active cancer4.1210.824–20.5990.085Heart failure2.5010.936–6.6830.068Hemoglobin0.8420.670–1.0580.140 Disclosures:No relevant conflicts of interest to declare.

PP-40. Two cases of intracranial haemorrhage in term neonates after uneventful vaginal delivery

PP-40. Two cases of intracranial haemorrhage in term neonates after uneventful vaginal delivery

Safety and feasibility of intraarterial eptifibatide as a revascularization tool in acute ischemic stroke

Experience with the use of platelet glycoprotein (GP) IIb-IIIa inhibitor eptifibatide in patients with ischemic stroke is limited. The authors report the off-label use of intraarterial eptifibatide during endovascular ischemic stroke revascularization procedures for reocclusion after documented recanalization or formed fresh thrombi in distal vessels that were inaccessible to endovascular devices. Patients who received intraarterial eptifibatide were identified from a prospectively collected database of patients in whom endovascular revascularization for acute ischemic stroke was attempted between 2005 and 2008. Data were analyzed retrospectively. The intraarterial eptifibatide dose was a single-bolus dose of 180 μg/kg body weight. Primary outcome measures were angiographic recanalization (Thrombolysis in Myocardial Infarction Grade 2 or 3), symptomatic intracranial hemorrhage rate, overall mortality rate, and favorable 3-month modified Rankin Scale score (≤ 2). The study included 35 patients (mean age 62 years, range 18-85 years). The median presenting National Institutes of Health Stroke Scale score was 13. Two patients received intravenous tissue plasminogen activator before endovascular therapy. The median time from symptom onset to therapy initiation was 230 minutes (range 90-1370 minutes). Twelve patients (34%) received intraarterial tissue plasminogen activator without mechanical measures. Mechanical revascularization measures used were Merci retriever in 19 (54%), Penumbra device in 1 (3%), balloon angioplasty in 15 (43%), and stent placement in 22 (63%) patients. The mean dose of intraarterial eptifibatide was 11.6 mg (range 5-16.6 mg). Partial-to-complete recanalization (Thrombolysis in Myocardial Infarction Grade 2 or 3) was achieved in 27 patients (77%). Postprocedure intracranial hemorrhage occurred in 13 patients (37%), causing symptoms in 5 (14%). In the 5 symptomatic intracranial hemorrhage cases, all patients but one presented more than 8 hours after symptom onset and all received intraarterial recombinant tissue plasminogen activator. The median discharge National Institutes of Health Stroke Scale score was 7 (range 0-17). At 3 months postprocedure, 21 patients (60%) had a modified Rankin Scale score ≤ 2, and 8 patients (23%) had died. Adjunctive intraarterial eptifibatide is a feasible option for salvage of reocclusion and thrombolysis of distal inaccessible thrombi during endovascular stroke revascularization. Its safety and efficacy need to be studied further in larger, multicenter, controlled studies.

Intracranial Hemorrhage Following Neuroendovascular Procedures with Abciximab is Associated with High Mortality: A Multicenter Series

Abciximab is being used as an adjunct to neuroendovascular procedures both to prevent and treat ischemic sequelae. Experience with abciximab in this setting is limited; major bleeding complications, including fatal intracranial hemorrhage (ICH), are of particular concern. We report our multicenter experience with ICH following the administration of abciximab during neuroendovascular procedures. We identified neuroendovascular procedures (including cerebral angiograms, aneurysm coiling procedures, angioplasty/vascular stenting procedures, and emergent revascularization procedures) that used abciximab at Mayo Clinic Hospitals in Rochester, Jacksonville, and Phoenix between November 2000 and April 2009. Cases of periprocedural ICH were identified and pertinent demographic, historical, procedural, radiographic, and laboratory data were collected. Clinical outcome was measured either at death or discharge by the Glasgow Outcome Scale (GOS). Abciximab was used in 51 neuroendovascular procedures; 9 cases of ICH were identified. Procedures performed and indications for abciximab use varied. Route of abciximab administration included IV bolus only (n = 4), IA bolus followed by IV infusion (n = 3), IV bolus followed by IV infusion (n = 1), and IV infusion without preceding bolus (n = 1). All but 1 of the patients received concomitant periprocedural antiplatelet, anticoagulant, or thrombolytic agents. Eight of the 9 cases of ICH were detected within 7 h of abciximab administration. ICH pattern varied. Four patients died following ICH. Adjunctive use of abciximab to prevent or treat ischemic sequelae during neuroendovascular procedures is associated with a high risk of ICH (18%). We report 9 cases of ICH associated with abciximab administration during neuroendovascular procedures with 44% mortality.

A clinical study of 32 cases with HELLP syndrome

Objective To analyze the clinical presentation and maternal-neonatal outcome of HELLP syndrome.Methods 32 cases with HELLP syndrome from January 2003 to January 2009 were analyzed retrospectively.Results The incidence of HELLP syndrome in preeclampsia was 3.7%.Complete HELLP were 17 cases,partial HELLP were 15 cases.Two pregnant women died(one case of intracranial hemorrhage,one case of acute left cardiac failure),the mortality was 6.3%.Five newborns died,the mortality was 15.6%.The main materal complications were DIC(8 cases),placental abruption(2 cases),intracranial hemorrhage(2 cases).The main perinatal complications were preterm labor(20 cases),newborn asphysia(17 cases),SGA(15 cases).Conclusion HELLP syndrome is one of the most serious obstetric complications,early diagnosis,early therapy,controlling hypertension and termination of pregnancy in time are most important for treatment. Key words: Hypertension,pregnancy; HELLP Syndrome

A case of intracranial hemorrhage in a neonate with congenital factor VII deficiency

Congenital factor VII deficiency is a rare autosomal-recessive bleeding disorder. Bleeding manifestations and clinical findings vary widely, ranging from asymptomatic subjects to patients with hemorrhages that may cause significant handicaps. Treatment has traditionally involved factor VII(FVII) replacement therapy using fresh frozen plasma, prothrombin complex concentrates or plasma-derived FVII concentrates. Recombinant activated FVII (NovoSeven®) is currently considered the first-line treatment for replacement therapy of FVII deficiency. Here we present a case of severe intracerebral and intraventricular hemorrhage in a neonate with congenital FVII deficiency.

Intracranial hemorrhage (ICH) in children with immune thrombocytopenia (ITP): study of 40 cases

AbstractIntracranial hemorrhage (ICH) is a rare but devastating complication of childhood immune thrombocytopenia purpura (ITP). A survey of ICH from 1987 to 2000 identified cases of ICH in childhood ITP in the United States. Forty patients with ICH and 80 matched ITP control subjects were accrued. The estimated incidence of ICH was 0.19% to 0.78%. Platelet counts were less than 20 × 109/L in 90% and less than 10 × 109/L in 75% of children with ICH. Eighteen (45%) children developed ICH within 7 days of diagnosis of ITP; for 10 of these, ICH was the presenting feature of ITP. Twelve (30%) children had chronic ITP. Head trauma and hematuria were the most prominent features associated with ICH, identified in 33% and 22.5% of the patients with ICH and 1 and none of the controls (both P < .001). Bleeding beyond petechiae and ecchymoses was also linked to ICH. Mortality was 25%; a further 25% had neurologic sequelae. Strategies by which high-risk children could be identified were considered, and the costs of preventive combination treatment were estimated. Children with severe thrombocytopenia plus head trauma and/or hematuria appeared to be at particularly high risk of ICH. Aggressive treatment of these children may be appropriate.

TROPICS 2: A Phase III, Open-Label, Single-Arm Study of Tenecteplase for Restoration of Function in Dysfunctional Central Venous Catheters.

Abstract 1074Poster Board I-96 Introduction:For many patients, central venous catheters (CVCs) are the only option for vascular access. Thrombotic occlusion is a common complication of CVCs and can prevent delivery of treatment. The objectives of this phase III, open-label, single-arm study were to evaluate the safety and efficacy of the thrombolytic agent tenecteplase, a fibrin-specific recombinant tissue plasminogen activator, in restoring function to occluded CVCs. Methods:Pediatric and adult subjects with dysfunctional non-hemodialysis CVCs, defined by the inability to withdraw 3 mL of blood (1 mL of blood for subjects weighing <10 kg) were eligible. Subjects received intraluminal tenecteplase at a dose of up to 2 mL (2 mg); subjects weighing <30 kg received instillations of tenecteplase equal to 110% of the internal lumen volume (maximum volume, 2 mL). Tenecteplase was allowed to dwell in the lumen for up to 120 minutes. CVC function, defined as the ability to both withdraw 3 mL of blood or fluid and infuse 5 mL of normal saline (1 mL and 3 mL, respectively, for subjects <10 kg), was assessed at 15, 30, and 120 minutes after drug instillation. If function was not restored at 120 minutes, the initial dose was withdrawn, and a second dose was instilled for up to 120 minutes. CVC assessments were repeated as for the first dose. The primary efficacy endpoint was restoration of CVC function within 120 minutes after a single administration of tenecteplase. All adverse events (AEs) were documented from instillation of the first tenecteplase dose through 48-96 hours after treatment. Targeted AEs (intracranial hemorrhage, major bleeding, embolic events, thrombosis, catheter-related bloodstream infection [CRBSI], and catheter-related complications) and study-drug–related serious AEs were recorded through 7 days after treatment. Results:Tenecteplase was administered to 246 subjects (mean age 43.6 years; range, 0-92 years), 72 (29.2%) of whom were under 17 years of age. Most subjects had a port catheter (69.5%), and the most frequent indication for catheter insertion was chemotherapy (78.0%). Most subjects (186; 75.6%) received only a single dose of tenecteplase, and 60 (24.3%) subjects required a second dose of tenecteplase. Restoration of CVC function was achieved in 177 (72.0%) subjects within 120 minutes after the first dose of tenecteplase. Following instillation of up to 2 doses of tenecteplase, CVC function was restored in 200 (81.3%) subjects, with similar restoration rates observed in pediatric (83.3%) and adult (80.5%) subjects. Among those who had treatment success and underwent catheter assessment within 7 days of treatment, 111 (81.0%) subjects maintained catheter patency. Thirty-one (12.6%) subjects experienced a treatment-emergent AE; the most common events were pyrexia (6 subjects), neutropenia (3 subjects), and nausea (2 subjects).Two targeted AEs were reported, both CRBSIs, but neither event was judged by the investigator to be related to tenecteplase; and in both cases, blood cultures were subsequently reported negative. No cases of intracranial hemorrhage, major bleeding, thrombosis, embolism, or catheter-related complications were reported. One serious AE, an allergic hypersensitivity reaction, was judged to be related to tenecteplase; however, this subject was concurrently receiving a chemotherapeutic agent, which the investigator also considered to be related to the AE. Conclusions:Serial administration of up to 2 doses of tenecteplase into CVCs is safe and effective for restoration of catheter function in pediatric and adult subjects with dysfunctional CVCs. Disclosures:Off Label Use: Tenecteplase is a thrombolytic agent under study for clearance of dysfunctional central venous catheters. Shulman:Takeda Pharmaceuticals: Research Funding; NPS Pharmaceuticals: Consultancy. Jacobs:Speaking engagements unrelated to commercial activity: Honoraria. Blaney:Genentech: Employment, Equity Ownership. Ashby:Genentech: Employment, Equity Ownership. Gillespie:Quintiles: Employment, Quintiles is a contract research organization contracted by Genentech to execute the TROPICS trials.. Begelman:Genentech: Employment, Equity Ownership.

Retrospective Review of Life-Threatening Bleeds in Paediatric ITP.

Abstract 4453Immune thrombocytopenia (ITP) is an uncommon disorder of childhood. Most children recover quickly regardless of intervention, but severe bleeding develops in approximately 3%. Intracranial haemorrhage (ICH) is by far the most feared complication, occurring in 0.1-0.5%. Pharmacotherapy is available to transiently increase platelet counts, but introduction of British clinical guidelines in 1992 has resulted in a sharp decline in the number of children receiving such treatment.The aim of this survey is to establish the current UK incidence of intracranial and other life-threatening haemorrhages in ITP, and whether or not children developing such complications have other risk factors for bleeding.UK paediatricians were mailed a questionnaire asking to report the number of cases of ITP per year, and any cases of intracranial haemorrhages (ICH) in the previous ten years or other life-threatening haemorrhages in the past five years. Consultants reporting patients were asked to complete a form requesting detailed information on the child and the circumstances surrounding their bleed.844 annual cases of ITP were reported from 145 centres; 672 of these were acute presentations and 240 were chronic. 24 cases of ICH and 19 cases of life-threatening bleed were identified, giving an annual incidence of 0.3% and 0.5% respectively. Gastrointestinal haemorrhage was the most commonly reported life-threatening bleed, and in six cases, ICH and life-threatening bleeds occurred in the same child.The incidence of ICH in ITP may be higher than previously reported in the UK; the reason behind this increase remains unknown and support the need for larger international collaborative studies. Disclosures:No relevant conflicts of interest to declare.

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.

Cranial subdural haematoma: a rare complication of spinal anaesthesia

Cranial subdural haematoma: a rare complication of spinal anaesthesia