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Technologies that can record neural activity at cellular resolution at multiple spatial and temporal scales are typically much larger than the animals that are being recorded from and are thus limited to recording from head-fixed subjects. Here we have engineered robotic neural recording devices—‘cranial exoskeletons’—that assist mice in maneuvering recording headstages that are orders of magnitude larger and heavier than the mice, while they navigate physical behavioral environments. We discovered optimal controller parameters that enable mice to locomote at physiologically realistic velocities while maintaining natural walking gaits. We show that mice learn to work with the robot to make turns and perform decision-making tasks. Robotic imaging and electrophysiology headstages were used to record recordings of Ca2+activity of thousands of neurons distributed across the dorsal cortex and spiking activity of hundreds of neurons across multiple brain regions and multiple days, respectively.

ABSTRACTIntroductionAcute myeloid leukemia (AML) is an aggressive malignancy of clonal myeloid precursor cells. Curative therapy has classically involved the use of intensive induction chemotherapy followed by consolidation with additional chemotherapy or allogeneic hematopoietic stem cell transplant. For many patients, such an approach is prohibitive because of high treatment-related toxicities. Advancements in the molecular understanding of AML have led to the introduction of new targeted therapies that are changing the treatment landscape for AML.Areas coveredWe review emerging small molecule inhibitors that have shown preclinical efficacy for the treatment of AML. The compounds discussed affect apoptosis, p53-mediated interactions, transcriptional regulation, and cellular metabolism. We performed a literature search of PubMed and primarily included relevant sources published from 2000 to the present, though earlier sources are also referenced.Expert opinionMost clinical trials for AML currently employ novel targeted therapies that demonstrate promising activity in preclinical models. We anticipate that new small molecule inhibitors will continue to enter the clinical realm and alter the treatment paradigm for AML. In a field where clinical advancement was comparatively slow for many years, it appears that we are now starting to see the rapid growth borne out of the deepening molecular understanding of AML.

ABSTRACTCrystalline-silicon (c-Si) photovoltaic (PV) modules are clearly dominated by material costs, especially by the costs of the silicon wafer. Currently, the efficiency of the cells and modules is the main advantage to bring down the costs even more. Here, optimised c-Si PV module is proposed after introducing a back surface field (BSF) layer and transparent conductive electrode by simulating the performance of different c-Si solar-cell modules. First, simulation has been carried out on a simple p–n junction solar cell for optimised layer thickness and different doping density of acceptor and donor atoms. To further reduce the thickness of base region, a highly doped p+layer was introduced at the back surface of base region as the BSF. The solar cell was optimised with BSF layer to get power conversion efficiency (PCE) of 16.35%. Furthermore, an anti-reflective layer of indium tin oxide (ITO) with optimised thickness was introduced as a front surface electrode. This device model showed an increased short-circuit current (Jsc) and open-circuit voltage (Voc) with an improved efficiency. This work is a fundamental study to achieve reasonable good efficiencies at low cost through optimisation of the BSF layer and transparent conductive electrodes.

Background:Obe-cel is an autologous chimeric antigen receptor (CAR) T cell product with a novel CD19 binding domain CAT conferring a fast antigen off-rate designed to mitigate safety concerns and improve persistence over approved CD19 CAR T therapies. Early results from the pivotal FELIX study Phase IIA cohort (N=94) were recently presented (Roddie C et al. J Clin Oncol 2023;41[16 Suppl]:7000). We report findings from a pooled analysis of all patients (pts) treated to date with obe-cel in the FELIX Phase Ib/II study (NCT04404660), with a focus on pts with low leukemia burden prior to obe-cel infusion.

Konopleva: Agios: Research Funding; Ablynx: Research Funding; Calithera: Research Funding; Cellectis: Research Funding; Eli Lilly: Research Funding; Kisoji: Consultancy; Amgen: Consultancy; Forty-Seven: Consultancy, Research Funding; Stemline Therapeutics: Consultancy, Research Funding; F. Hoffmann La-Roche: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Reata Pharmaceutical Inc.;: Patents & Royalties: patents and royalties with patent US 7,795,305 B2 on CDDO-compounds and combination therapies, licensed to Reata Pharmaceutical; Rafael Pharmaceutical: Research Funding; Ascentage: Research Funding; AstraZeneca: Research Funding; Sanofi: Research Funding. Borthakur:PTC Therapeutics: Consultancy; GSK: Research Funding; PTC Therapeutics: Research Funding; BioTherix: Consultancy; Nkarta Therapeutics: Consultancy; Treadwell Therapeutics: Consultancy; Abbvie: Research Funding; Jannsen: Research Funding; Oncoceutics: Research Funding; Incyte: Research Funding; Novartis: Research Funding; Curio Science LLC: Consultancy; FTC Therapeutics: Consultancy; Xbiotech USA: Research Funding; Polaris: Research Funding; AstraZeneca: Research Funding; BioLine Rx: Consultancy; Cyclacel: Research Funding; Argenx: Consultancy; BioLine Rx: Research Funding; BMS: Research Funding. Jabbour:Adaptive Biotechnologies: Other: Advisory role, Research Funding; Amgen: Other: Advisory role, Research Funding; BMS: Other: Advisory role, Research Funding; Genentech: Other: Advisory role, Research Funding; Takeda: Other: Advisory role, Research Funding; AbbVie: Other: Advisory role, Research Funding; Pfizer: Other: Advisory role, Research Funding. Pemmaraju:Stemline Therapeutics: Honoraria, Research Funding; Celgene: Honoraria; Pacylex Pharmaceuticals: Consultancy; Affymetrix: Other: Grant Support, Research Funding; Samus Therapeutics: Research Funding; Cellectis: Research Funding; DAVA Oncology: Honoraria; Plexxikon: Research Funding; Incyte Corporation: Honoraria; SagerStrong Foundation: Other: Grant Support; Daiichi Sankyo: Research Funding; MustangBio: Honoraria; AbbVie: Honoraria, Research Funding; Roche Diagnostics: Honoraria; Blueprint Medicines: Honoraria; Novartis: Honoraria, Research Funding; LFB Biotechnologies: Honoraria. Kadia:Novartis: Honoraria; Cyclacel: Research Funding; Pfizer: Honoraria, Research Funding; Cellenkos: Research Funding; Genentech: Honoraria, Research Funding; JAZZ: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Celgene: Research Funding; Incyte: Research Funding; Amgen: Research Funding; BMS: Honoraria, Research Funding; Astellas: Research Funding; Ascentage: Research Funding; Pulmotec: Research Funding; Astra Zeneca: Research Funding. Short:Takeda Oncology: Consultancy, Honoraria, Research Funding; Amgen: Honoraria; Astellas: Research Funding; AstraZeneca: Consultancy. Burger:AstraZeneca: Consultancy; Pharmacyclics, an AbbVie company: Consultancy, Research Funding, Speakers Bureau; Gilead Sciences: Consultancy, Research Funding; Janssen Pharmaceuticals: Consultancy, Speakers Bureau; Beigene: Research Funding, Speakers Bureau; TG Therapeutics: Research Funding, Speakers Bureau. Daver:Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Trovagene: Research Funding; Fate Therapeutics: Research Funding; ImmunoGen: Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees; Trillium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Syndax: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Research Funding; Servier: Research Funding; Genentech: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novimmune: Research Funding. Kantarjian:Abbvie: Honoraria, Research Funding; Delta Fly: Honoraria; Janssen: Honoraria; Oxford Biomedical: Honoraria; Ascentage: Research Funding; Sanofi: Research Funding; Actinium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Research Funding; BioAscend: Honoraria; Adaptive biotechnologies: Honoraria; Novartis: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Jazz: Research Funding; Immunogen: Research Funding; Daiichi-Sankyo: Honoraria, Research Funding; BMS: Research Funding; Aptitute Health: Honoraria. Garcia-Manero:AbbVie: Honoraria, Research Funding; Acceleron Pharmaceuticals: Consultancy, Honoraria; Amphivena Therapeutics: Research Funding; Astex Pharmaceuticals: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Helsinn Therapeutics: Consultancy, Honoraria, Research Funding; H3 Biomedicine: Research Funding; Jazz Pharmaceuticals: Consultancy; Merck: Research Funding; Novartis: Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Onconova: Research Funding. Verma:Medpacto: Research Funding; acceleron: Consultancy, Honoraria; Janssen: Research Funding; BMS: Consultancy, Research Funding; stelexis: Current equity holder in private company. DiNardo:Jazz: Honoraria; ImmuneOnc: Honoraria; Agios: Consultancy, Honoraria, Research Funding; Calithera: Research Funding; Syros: Honoraria; Novartis: Consultancy; Celgene: Consultancy, Honoraria, Research Funding; Notable Labs: Membership on an entity's Board of Directors or advisory committees; MedImmune: Honoraria; Daiichi Sankyo: Consultancy, Honoraria, Research Funding; Takeda: Honoraria; AbbVie: Consultancy, Honoraria, Research Funding.CB-839, glutaminase inhibitor, investigation for use in advanced MDS

Background:

Introduction: Individualization of factor VIII (FVIII) prophylaxis dosing frequency is recommended in order to optimize treatment effectiveness in hemophilia A patients. While previous studies have shown long-term efficacy of BAY 81-8973, its long-term effectiveness in subgroups of patients receiving lower frequency prophylaxis (2x/week) has not been investigated. This post-hoc analysis assessed the association of BAY 81-8973 prophylaxis frequency with treatment adherence and long-term bleed outcomes in the LEOPOLD I extension study.

The role of pharmacokinetic (PK) assessment of factor VIII (fVIII) plasma levels in hemophilia A patients (pts) is evolving. For two decades at our center and many others, full or “modified” PK studies were based on multiple levels drawn before and for several hours following infusion. This required IV access for frequent sampling as well as substantial staff, patient, and parent time. A practical consequence was that PK assessment was reserved for pts with concern for poor factor survival. Recently Björkman, Collins et al reported use of population-based PK sampling to obtain accurate half-life (t1/2) determination by limited blood sampling (2 levels only, 12–36 hours post dose, “Day 2”) in adults with hemophilia A [Haemophilia 16:597, 2010]. The aim of this study was to evaluate the applicability and practical use of these principles in a large pediatric hemophilia clinic, with a long-term goal of individualizing factor VIII dosing.For this IRB-approved chart review, 27 pts were identified through Hemophilia Center records and a hospital EMR search strategy, who had fVIII PK studies since 2002 at Boston Children's Hospital. Four of 27 had an inhibitor at the time of assessment and were excluded from analysis. Maximum post-infusion fVIII concentrations (Cmax) were estimated from the TCI Works Program [Björkman, Haemophilia 17:e239, 2011]. Graphical and statistical analyses were conducted in GraphPad Prism 5.01. Graphical models in Prism used non-linear least squares fit to a one phase exponential decay curve with the “terminal plateau” parameter arbitrarily constrained to 0.5% (0.005U/ml fVIII) for severe hemophilia A.Forty sets of PK studies were analyzed from 23 pts, median age 7.9 years, and including 8/23 patients (35%) with former inhibitors. The median z-score for BMI was +0.3; obesity was rare. All FDA approved recombinant fVIII brands were represented. The average t1/2 of fVIII in our pts was 6.8 ± 2.1 hours. 52% (12/23) of patients had PK values only within the first 8 hours after an infusion (plus pre-infusion “trough”). Eight non-inhibitor pts contributed multiple sets of PK to the study, over a maximum time interval of 8 years, with negligible variability over time. Due to the commonly observed rapid early fVIII clearance (“biphasic kinetics”), estimates of t1/2 based on Day 2 time points (after 12–24 h when available) are longer than estimates based on points within the first several hrs post infusion (“Day 1”) for pts in which both “Days” were available. Figure A demonstrates this effect in one pt, and shows t1/2 estimated from early vs. late samples. An example of Day 2 sampling alone is shown in Figure B.Second-day fVIII sampling shows promise in pediatric hemophilia A pts as published for adult pts. Testing our entire prophylaxis population by this method has significant implications for individualized vs. fixed dose prophylactic dosing strategies. In non-inhibitor pts, our center has historically used every-other-day prophylactic fVIII dosing at 25 U/kg usually not modified for individual PK. The recognition that Day 2 sampling is equal or superior to detailed first-day testing could result in manifold improvements in (a) pt satisfaction; (b) ability to test all prophylaxis pts rather than those with perceived bleeding risk; (c) ability to individualize treatment models based on PK assessments; (d) reduced testing cost per pt; and (e) potential large savings on a population basis for factor utilization. Individualized dose tailoring and kinetic analyses offer the potential for better pt health and decreased cost of hemophilia treatment.Saxena: Bayer: Research Funding; Novo Nordisk: Research Funding. Neufeld:Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; Bayer: DSMB membership, DSMB membership Other; Baxter: Research Funding.

Abstract 3368

Khojasteh: Grifols S.A.: Research Funding. Kato:Grifols S.A.: Research Funding. Parikh:Grifols S.A.: Research Funding. Singleton:Grifols S.A.: Research Funding. Tebbi:Grifols S.A.: Research Funding. Cromwell:Grifols S.A.: Research Funding. Fu:Grifols S.A.: Research Funding. Kessler:Grifols S.A.: Research Funding. Letzer:Grifols S.A.: Research Funding. Ritchie:Grifols S.A.: Research Funding. Sexauer:Grifols S.A.: Research Funding. Saxena:Grifols S.A.: Research Funding. Sirpal:Grifols S.A.: Research Funding. Torres:Grifols S.A.: Research Funding. Loriya:Grifols S.A.: Research Funding. Kovaleva:Grifols S.A.: Research Funding. Sandoval:Grifols S.A.: Research Funding. Sanz:Grifols S.A.: Research Funding. Julià:Grifols S.A.: Research Funding. Montañés:Grifols S.A.: Employment. Navarro:Grifols S.A.: Employment.

Abstract 4669

Studies assessing the safety, tolerability and efficacy of a licensed drug are of utmost value for caregivers, patients and authorities to overcome the shortcomings of pre-licensing trials and to obtain information on the behavior of a drug in routine clinical conditions. Moreover, there is a paucity of data addressing the clinical outcome of treatment strategies in patients with severe hemophilia A, an especially vulnerable subset that presents the highest prevalence of antibody inhibitors. Late onset inhibitors may arise in patients who have accumulated hundreds of exposure days or after an intensive treatment episode.To assess the immunogenicity and overall safety associated with long-term use of Alphanate®, a highly purified plasma-derived factor VIII concentrate containing high-molecular weight multimers of von Willebrand Factor, a prospective, non-randomized, multicenter, post-authorization surveillance study was initiated in 2002 with the intention of involving at least 50 evaluable patients. Only previously treated patients (PTPs) diagnosed with severe hemophilia A (<1% FVIII:C) between 6 and 65 years of age who have been previously treated with plasma-derived Factor VIII products other than Alphanate® are eligible to be enrolled. The primary endpoint of the study was the incidence of Factor VIII inhibitors and secondary endpoints were aimed to evaluate product tolerability and hemostatic efficacy. Treatment with Alphanate® was given as needed for routine prophylaxis, bleeding episodes or hemorrhage and prior to physiotherapy or surgical procedures.As of December of 2008, the investigation had recruited 31 patients of which 29 (94%) had received at least one infusion of Alphanate® and 21 (68%) had completed the planned 24-30 month observational period with a minimum of 50 exposure days. The mean dose infused was 33.6 IU/kg (range: 18.3-73.1 IU/kg) and volume per patient per infusion was 1774 IU (range 395-3329 IU). Of the 29 subjects that had received approximately a total of 6.9 million units of Alphanate® through 4704 infusions, none had developed inhibitors (0%) and none had seroconverted for hepatitis A, B, C or HIV-1/2. Overall, 12 (42.6%) subjects experienced a total of 50 commonly reported adverse events (AEs), 3 classified as serious, none of which were considered related to the study drug and none occurred during drug infusion. Furthermore, no patients had withdrawn from the study because of AEs and there were no reports of thromboembolic or other thrombotic events.The results included herein confirm the excellent immunogenicity and overall safety profile of Alphanate® in the treatment of PTPs with severe hemophilia A.Páez: Instituto Grifols S.A.: Employment. Pinciaro:Grifols Biologicals Inc.: Employment. Woodward:Instituto Grifols S.A.: Employment.

Abstract 3141

Objective To identify renal transplant patients at a higher risk for allograft thrombosis and develop a risk stratification protocol for post-operative anticoagulation. Background According to the North American Pediatric Renal Transplant Cooperative Study data, vascular thrombosis is responsible for 12% of renal transplant failures. Congenital and acquired prothrombotic disorders have recently been found to play a major role in defining outcome of the renal transplants. Methods In 2007, we initiated universal screening for acquired and congenital thrombophilic risk factors for all renal transplant patients prior to transplant. They were assigned a risk category (Level I-IV) based on the presence of thrombophilic risk factors and their post-operative anticoagulation plan was pre-determined based on their risk level (Table). Low-dose unfractionated heparin drip was initiated a few hours after the transplant and titrated to achieve a 1.5 fold aPTT level. Anticoagulation was changed to low molecular weight heparin (LMWH) on day 2–4, when the risk of major bleed was over, and the serum creatinine had normalized. Result Nine patients have been screened and 8/9 were found to be at high risk for thrombosis (Level II or III). The prothrombotic risk factors identified were Prothrombin gene mutation (2), MTHFR (8), Lupus anticoagulant (2) and low protein S (2). Five patients have undergone renal transplant, and have been treated with LMWH post-operatively as per plan, with successful outcome. No patient has developed allograft thrombosis. 1/5 patients developed a peri-renal hematoma requiring evacuation, but completed prophylactic LMWH therapy. Conclusion Renal allograft thrombosis is preventable. Universal screening can stratify risk and allow an effective intervention to reduce that risk. Our Institution has developed a unique risk stratification protocol to identify patients at high risk for allograft thrombosis and prevent this complication by post-operative anticoagulation. Risk Categorization and Management Plan Risk Level Thrombophilia Management Level I Evidence of Thrombophilia (other than MTHFR) and previous thrombosis Heparin postoperatively and then LMWH bid for 6 months Level II Evidence of Thrombophilia (other than MTHFR), No history of thrombosis Heparin postoperatively, LMWH bid for 3 months, then qd for 3 months Level III MTHFR with normal homocysteine Heparin postoperatively, then LMWH qd for 3 months Level IV No evidence of thrombophilia No anticoagulation

Objective To identify renal transplant patients at a higher risk for allograft thrombosis and develop a risk stratification protocol for post-operative anticoagulation.

Objective: To determine if variability in clinical phenotype of severe hemophilia patients is influenced by the percentage of coated-platelets. Background: Co-activation of platelets with thrombin and collagen results in a unique subset of platelets, with high levels of alpha granule proteins on their surface, such as Factor V, fibrinogen, von Willebrand factor, and thrombospondin. This subset of activated platelets is referred to as coated-platelets (J. Thromb. Haemostasis3:2185, 2005). The high concentration of adhesive and prohemostatic proteins observed on coated-platelets provides a unique procoagulant locus that may influence the number of bleeding episodes in patients with severe hemophilia. Methods: After informed consent, 3–5 ml of blood was drawn from patients with severe hemophilia (Factor VIII <1%) and healthy controls. The number of bleeding episodes reported in the last 6 months was taken as an indicator of clinical phenotype. Results: In 6 patients with more than 3 bleeds reported in the last 6 months (14 ± 4.9 bleeds; mean ± 1SD), the average coated-platelets percentage was 22.3 ± 11.2%. In 17 patients with 3 or less bleeds (1.6 ± 1.3) in the last 6 months, the average coated-platelets percentage was 37.6 ± 12.0%, a difference that was statistically significant (p=0.012). In healthy controls (n=12), the mean coated-platelets were 30.2 ± 9.5%. Conclusion: A higher percentage of coated-platelets may provide a better procoagulant locus for residual Factor VIII, thereby reducing the number of clinical bleeding episodes and partially explaining some variability observed in clinical phenotype of severe hemophilia.

Objective: To determine individual/institutional practices at hemophilia treatment centers (HTCs) regarding management of severe hemophilia patients during minor surgery (e.g., central venous line insertion, cataract surgery, lymph node biopsy), both in the absence and presence of low and high titer inhibitors to Factor VIII (FVIII). Background: The management of hemophilia patients undergoing surgery has changed over the past 20 years as product choice and availability has evolved. Individual preference and experience may affect treatment decisions in the absence of data from clinical trials. Methods: The survey was distributed to both adult and pediatric hematologists at HTCs listed on the CDC website. 93 surveys were successfully emailed. Survey questions evaluated management of minor surgery, both in the absence and presence of a low and high titer inhibitor to FVIII. Results: Surveys from 32 HTCs were received. Twenty-two respondents were affiliated with a University Hospital. For patients without inhibitor, the majority of respondents prefer a pre-operative bolus dose of FVIII 50 U/kg (73%, 22/30; range 25–50 U/kg); only 3 respondents reported a continuous infusion (range 4–8 u/kg/hr). For the post-operative dose, most (n=22) prefer a bolus dose (25–50 U/kg); only 6 reported using a continuous dose (range 2–8 U/kg/hr). Total number of days treated pre-operatively was reported as less than a day in 88% (23/26) respondents; days of post operative treatment ranged from 1–14 with a median of 4 days (n=22). Desired FVIII level ranged from 50–100% for 1–10 days. Fifty percent (15/30) reported adjuvant use of Amicar. For patients with high inhibitor levels no one reported a pre or post operative FVIII bolus or continuous infusion rate. Fifty percent (9/18) reported adjuvant Amicar use. The reported rFVIIa dose in patients with high titer inhibitors, ranged from 90–200 mcg/kg (most commonly 90 mcg/kg), usual frequency of every 2 hours, for a range of 1–10 days. The reported FEIBA dose in patients with high titer inhibitors, ranged from 50–100 U/kg (most commonly 75–100 U/kg with a frequency of every 12 hours, for 1–10 days. Conclusion: Substantial practice variations exist in managing minor surgeries in hemophilia patients, both with and without low and high titer inhibitors, as is evident with this survey.

Objective: To determine individual/institutional practices at hemophilia treatment centers (HTCs) regarding management of severe hemophilia patients during major surgery (e.g., knee replacement, appendectomy), both in the absence and presence of low and high titer inhibitors to Factor VIII (FVIII). Background: There are considerable variations in the management of hemophilia patients undergoing surgery. The use of alternative products like Amicar, recombinant Factor VIIa (rFVIIa) and FEIBA is also growing. Methods: The survey was distributed to both adult and pediatric hematologists at HTCs listed on the CDC website. Ninety-three surveys were successfully emailed. Survey questions evaluated management of hemophilia patients during major surgical procedures, both in the absence and presence of a low and high titer inhibitor. Results: Surveys from 32 HTCs were received. Twenty-two respondents were affiliated with a University Hospital. For patients without inhibitor, the majority of respondents prefer a pre-operative bolus dose of 50 U/kg (84%, 22/28, range 40–70 U/kg); 15 respondents prefer a continuous dose (range 2–8 U/kg/hr). For the post-operative dose, 11 reported a bolus dose, usually 25–50 u/kg; 17 reported using a continuous dose (range 2–8 U/kg/hr). Total number of days treated pre-operatively was reported as less than a day by 90% (18/20) respondents; days of post operative treatment ranged from 7–42 with a median of 13 days (n=22). Desired FVIII level ranged from 50–100% for 3– 15 days. Median number of days inpatient was 6 (n=21). Eight percent (2/25) reported adjuvant use of Amicar. Thirty-nine percent (11/28) reported use of thrombotic prophylaxis after surgery. For patients with high titer inhibitor levels, only 1 respondent reported a pre or post operative FVIII bolus or continuous dose. The reported rFVIIa dose in patients with high titer inhibitor, ranged from 90–270 mcg/kg (most reporting 90 mcg/kg), with most reporting a frequency of every 2 hours for a range of 1–14 days. The reported FEIBA dose in patients with high titer inhibitors ranged from 50–100 U/kg (most 75 U/kg) with most reporting a frequency of every 12 hours for 6–14 days. Sixty four percent (7/11) reported use of thrombotic prophylaxis after surgery. Conclusion: Substantial practice variations exist in managing major surgeries in hemophilia patients, both with and without low and high titer inhibitors. This data will assist in developing future clinical trials and practice guidelines for management of hemophilia patients undergoing surgical procedures.

Objective: To determine individual/institutional practices at hemophilia treatment centers (HTCs) regarding management of severe hemophilia patients during minor surgery (e.g., central venous line insertion, cataract surgery, lymph node biopsy), both in the absence and presence of low and high titer inhibitors to Factor VIII (FVIII).

Objective: To determine individual/institutional practices at hemophilia treatment centers (HTCs) regarding management of severe hemophilia patients during major surgery (e.g., knee replacement, appendectomy), both in the absence and presence of low and high titer inhibitors to Factor VIII (FVIII).

Objective:To determine if variability in clinical phenotype of severe hemophilia patients is influenced by the percentage of coated-platelets.