ALBERT

Description: Deep venous thrombosis (DVT) is a common postoperative complication in patients undergoing major orthopaedic surgery of the lower limbs, such as total hip replacement (THR), total knee replacement (TKR), or hip fracture surgery (HFS). In the absence of thromboprophylaxis, subclinical venous thrombosis rates as high as 60% have been reported when using systematic bilateral phlebography after orthopaedic surgery. As a result, routine pharmacological thromboprophylaxis with low-molecular-weight heparin (LMWH) or a new oral anticoagulant agent is strongly recommended in patients undergoing these procedures. With the availability of efficient and safe clotting factor concentrates, THR, TKR, as well as ankle arthrodesis are frequently performed in subjects with haemophilia suffering from chronic haemophilic arthropathy. Yet, pharmacological prophylaxis of venous thromboembolism (VTE) in this patient group remains controversial. With the exception of retrospective case reports and small series, the incidence of VTE disease in haemophilic patients after major orthopaedic surgery is still unclear. Surveys suggest that more than half of hemophilia treatment centers in the United States and Europe use thromboprophylaxis in patients with haemophilia (PWH) who require major orthopedic surgery. However, this is not supported by evidence or surgical practice guidelines, and simply increases the risk of bleeding in such patients. Given the aging nature of the haemophilia population and the incidence of joint disease, the question of the thrombotic risk associated with major orthopaedic surgery and joint replacement surgery in particular is highly relevant. Few studies have addressed this issue and more information is needed on which to base optimal preventive strategies for venous thrombosis in patients with haemophilia undergoing elective major orthopedic surgery. We here report the results of 2 parallel and independent prospective studies from Belgium and Norway currently evaluating by systematic US-Doppler imaging the incidence of subclinical deep venous thrombosis in consecutive haemophilic patients referred for major orthopaedic surgery. In Belgium, the study has so far included 36 different patients (32 HA, 4HB) undergoing 50 major orthopaedic procedures of the lower limbs. In Norway, the study has involved 29 patients (26 HA, 3 HB, all with severe haemophilia) undergoing 29 orthopaedic procedures, most of the lower limbs. In both countries, most patients were treated with continuous infusion of clotting factor concentrates and none of them did receive antithrombotic pharmacological prophylaxis. In the 2 studies that included in total 65 patients undergoing 79 major orthopaedic procedures, no case of clinically patent DVT or PE was detected (Table 1). In total there were 5 cases of DVT evidenced by US imaging which were all distal, not complicated by PE and treated with a short course of low-molecular weight heparin in most cases. The overall incidence of subclinical DVT calculated on the whole population was 6%. In conclusion, these data provide for the first time multicentric and imaging-based evidence that the risk of DVT following major orthopaedic surgery among patients with haemophilia undergoing major orthopaedic surgery is very low and that systematic pharmacological thromboprophylaxis in this specific population is for most patients not required. The two studies are still ongoing and should include a larger number of participants in the future. Table 1Characteristics of patients with haemophilia undergoing major orthopaedic surgeryHTC BrusselsHTCOsloTotalPatients362965Haemophilia A322658Haemophilia B437Severe252954Moderate909Mild202Procedures502979Knee301141Ankle81220Hip729Femur404Lumbar101Elbow044Venous thrombosis415HTC: Haemophilia Treatment Center Disclosures No relevant conflicts of interest to declare.

Description: Introduction BAY 94-9027 is a B-domain-deleted recombinant factor VIII (FVIII) that is site-specifically PEGylated with a 60-kDa (2 × 30-kDa) polyethylene glycol (PEG) to extend its half-life. The efficacy and safety of BAY 94-9027 as prophylactic and on-demand therapy for patients with severe hemophilia A were demonstrated in the phase II/III PROTECT VIII trial and its extension. We present an analysis of efficacy and safety outcomes in patients from PROTECT VIII who had completed at least 5 years of treatment as of 31 January 2018. Methods PROTECT VIII was a partially randomized, open-label trial of 134 males aged 12-65 years with severe hemophilia A (FVIII 〈 1%) and ≥ 150 FVIII exposure days (ED). Prophylaxis patients received BAY 94-9027 25 IU/kg twice weekly for a 10-week run-in period. Patients with ≤ 1 spontaneous, joint or muscle bleed during this period were randomized to 45-60 IU/kg every 5 days (E5D) or 60 IU/kg every 7 days (E7D) for the main 26-week study period; patients enrolling after the randomization arms were full, or with ≥ 2 bleeds in the run-in period, received 30-40 IU/kg twice-weekly (2×W). Twenty patients received BAY 94-9027 on demand as they had been prior to study. Following completion of the main PROTECT VIII study, patients could enter an extension, continuing BAY 94-9027 on any regimen used in the main study; 121 patients entered the extension, of whom 107 were on the prophylactic arm. Prophylaxis patients who switched regimen after the first 7 days of being in the extension were analyzed in a combined variable frequency (VAR) group. Annualized bleeding rate (ABR) and joint ABR were analyzed, along with safety outcomes. Results At the cut-off date, 33 patients had completed 5 years of treatment with BAY 94-9027 (2×W, n = 3; E5D, n = 10; E7D, n = 6; VAR, n = 14). Median number of infusions (range) was 363 (272-546), and median (range) annual factor consumption was 3385 (2732-5053) IU/kg. Median (range) ABR was 2 (0-15) in the full 5-year period, and 1 (0-12) for the final year. Corresponding joint ABRs were 1 (0-7) and 0 (0-7). Over the 5-year period, study drug-related adverse events (AE)s occurred in 6 patients (18.2%); no patients had a study drug-related serious AE. There were no discontinuations for AEs. No patients had confirmed FVIII inhibitors (titre ≥0.6 Bethesda units). Conclusions Thirty-three patients have received BAY 94-9027 prophylaxis for 5 years. The previously demonstrated efficacy of BAY 94-9027 was maintained across this period; in the last year of the extension median ABR was 1 and a third of patients were entirely free from bleeds. Consistent with the established safety profile of FVIII and with prior analyses of PROTECT VIII, there were few study drug-related AE and no evidence of any long-term toxicity of PEGylated product exposure. Taken together, these data support the use of BAY 94-9027 as a long-term treatment option for patients with hemophilia A. Disclosures Reding: Genentech: Other: Advisory Board. Hvitfeldt Poulsen:Primary investigator and national coordinator on clinical trials from Bayer Health Care: Other: Primary Investigator and national coordinator; Chaired an educational haemophilia symposium for nurses: Other: Chair; Nordic advisory boards (Bayer Health Care, Roche): Membership on an entity's Board of Directors or advisory committees; Lecturer on Nordic meeting on EHL FVIII (SOBI): Other: Lecturer . Tian:Bayer: Employment. Holme:Bayer, Biogen Idec, CSL Behring, Novo Nordisk, Pfizer, Shire and Sobi: Consultancy; Bayer, Octapharma, Pfizer and Shire: Research Funding.

Description: Abstract LBA-1 Background: Following acute deep vein thrombosis (DVT) of the lower limb, approximately 1 in 4 patients treated with anticoagulation (AC) and elastic compression stockings (ECS) in accordance with current guidelines, are still at risk for developing a chronically reduced functional outcome, i.e., the post-thrombotic syndrome (PTS). Additional treatment with catheter-directed thrombolysis (CDT) enhances clot removal and is suggested to favor venous competence and patency, thereby reducing the risk for PTS. This interventional therapy is expensive, associated with life-threatening bleeding, and converts an outpatient disease to an inpatient disease. However, it has become standard care in some centers despite a complete lack of evidence from randomized, controlled trials (RCT). The CaVenT study, representing the first RCT in this area, aimed to evaluate whether additional CDT with alteplase improved the functional outcome by reducing PTS development following acute iliofemoral DVT. Methods: The CaVenT study was an open, multicenter RCT that recruited patients from 20 hospitals in the Norwegian south-eastern health region. Patients of age 18–75 years with a first-time objectively verified acute iliofemoral DVT above mid-thigh level and symptoms for up to 21 days were eligible for recruitment. Study patients were randomly assigned with a 1:1 ratio to standard (control) treatment with AC and ECS grade II (30 mmHg) or to CDT with alteplase in addition to standard treatment. The present report concerns the primary clinical end-point; the frequency of PTS after 24 months follow-up. The study was designed to detect a reduction in PTS from 25% to 10% with a 5% significance level and with 80% power. Follow-up visits were conducted at 6 months ± 2 weeks and 24 months ± 4 weeks and included evaluation of PTS by the Villalta scale as recommended by the International Society on Thrombosis and Haemostasis. Iliofemoral patency was assessed with ultrasonography and air-plethysmography. A two-sided uncorrected Chi-square test was used for comparing dichotomous variables in the two treatment groups. Results: 209 patients with acute iliofemoral DVT were randomized during 2006–2009; 101 patients were allocated the CDT arm and 108 the control arm. At the completion of 24 months follow-up, data on clinical status were available and included in the intention to treat analyzes for 90 patients in the CDT arm and 99 control patients. Mean age was 51.5 years (SD 15.8), 36% were female, and mean duration of symptoms was 6.6 days (SD 4.6). 80/90 patients receiving CDT had successful lysis. At 24 months follow-up 37 (41.1%, 95% CI 31.5–51.4%) allocated additional CDT presented with PTS compared to 55 (55.6%, 95% CI 45.7–65.0%) in the control group (p=0.047), including one control with severe PTS. The difference in PTS corresponds to an absolute risk reduction of 14.4% (95% CI 0.2–27.9), and the number needed to treat was 7 (95% CI 4–502). No patients presented with venous ulcer. In total 20 bleeding complications were reported; 3 were classified as major and 5 as clinically relevant. The majority of bleedings were related to the puncture site. The major bleedings included 1 abdominal wall hematoma requiring blood transfusion, 1 compartment syndrome of the calf requiring surgery, and 1 inguinal puncture site hematoma. No bleeding led to a permanently reduced outcome, and there were no deaths, pulmonary embolism or cerebral hemorrhage related to CDT. Patients who had regained venous patency after 6 months, developed PTS in 38/103 (36.9%, 95% CI 28.2–46.5%) as compared to 49/80 (61.3%, 95% CI 50.3–71.2%) of patients with insufficient recanalization (p

Description: LBA-1 Background: Following acute deep vein thrombosis (DVT) of the lower limb, approximately 1 in 4 patients treated with anticoagulation (AC) and elastic compression stockings (ECS) in accordance with current guidelines, are still at risk for developing a chronically reduced functional outcome, i.e., the post-thrombotic syndrome (PTS). Additional treatment with catheter-directed thrombolysis (CDT) enhances clot removal and is suggested to favor venous competence and patency, thereby reducing the risk for PTS. This interventional therapy is expensive, associated with life-threatening bleeding, and converts an outpatient disease to an inpatient disease. However, it has become standard care in some centers despite a complete lack of evidence from randomized, controlled trials (RCT). The CaVenT study, representing the first RCT in this area, aimed to evaluate whether additional CDT with alteplase improved the functional outcome by reducing PTS development following acute iliofemoral DVT. Methods: The CaVenT study was an open, multicenter RCT that recruited patients from 20 hospitals in the Norwegian south-eastern health region. Patients of age 18–75 years with a first-time objectively verified acute iliofemoral DVT above mid-thigh level and symptoms for up to 21 days were eligible for recruitment. Study patients were randomly assigned with a 1:1 ratio to standard (control) treatment with AC and ECS grade II (30 mmHg) or to CDT with alteplase in addition to standard treatment. The present report concerns the primary clinical end-point; the frequency of PTS after 24 months follow-up. The study was designed to detect a reduction in PTS from 25% to 10% with a 5% significance level and with 80% power. Follow-up visits were conducted at 6 months ± 2 weeks and 24 months ± 4 weeks and included evaluation of PTS by the Villalta scale as recommended by the International Society on Thrombosis and Haemostasis. Iliofemoral patency was assessed with ultrasonography and air-plethysmography. A two-sided uncorrected Chi-square test was used for comparing dichotomous variables in the two treatment groups. Results: 209 patients with acute iliofemoral DVT were randomized during 2006–2009; 101 patients were allocated the CDT arm and 108 the control arm. At the completion of 24 months follow-up, data on clinical status were available and included in the intention to treat analyzes for 90 patients in the CDT arm and 99 control patients. Mean age was 51.5 years (SD 15.8), 36% were female, and mean duration of symptoms was 6.6 days (SD 4.6). 80/90 patients receiving CDT had successful lysis. At 24 months follow-up 37 (41.1%, 95% CI 31.5–51.4%) allocated additional CDT presented with PTS compared to 55 (55.6%, 95% CI 45.7–65.0%) in the control group (p=0.047), including one control with severe PTS. The difference in PTS corresponds to an absolute risk reduction of 14.4% (95% CI 0.2–27.9), and the number needed to treat was 7 (95% CI 4–502). No patients presented with venous ulcer. In total 20 bleeding complications were reported; 3 were classified as major and 5 as clinically relevant. The majority of bleedings were related to the puncture site. The major bleedings included 1 abdominal wall hematoma requiring blood transfusion, 1 compartment syndrome of the calf requiring surgery, and 1 inguinal puncture site hematoma. No bleeding led to a permanently reduced outcome, and there were no deaths, pulmonary embolism or cerebral hemorrhage related to CDT. Patients who had regained venous patency after 6 months, developed PTS in 38/103 (36.9%, 95% CI 28.2–46.5%) as compared to 49/80 (61.3%, 95% CI 50.3–71.2%) of patients with insufficient recanalization (p

Description: Abstract 22 Studies of in vivo survival of transfused platelets (PLTs) are usually performed by tracing PLTs labelled with radioactive isotopes. The aim of the present work was to develop a flow cytometry-based method without involving manipulation of PLTs before transfusion, where differences in HLA class I molecules between donor and recipient might be used to trace transfused PLTs. Of 14 fluorochrome-conjugated HLA class I monoclonal antibodies (mAbs) from 7 suppliers only 3 (anti-HLA A2, anti-HLA A9 and anti-HLA B27) were found satisfactory for HLA class I typing of PLTs. As earlier studies have claimed the existence of a considerable exchange of HLA class I antigens between plasma and PLTs, a series of experiments were conducted to examine the exchange of HLA A2, A9 and B27 class I antigens during storage for 4 days. Three pairs of HLA +ve and HLA −ve PLT aphaeresis products were collected in autologous plasma for each of the specificities HLA A2, HLA A9 and HLA B27. Cell-free plasma was prepared from an equal number of HLA +ve and HLA −ve whole blood units with the same specificities. Plasma-free PLTs and cell-free plasma were mixed and stored in PLT storage bags at 22°C in the following combinations: HLA +ve PLTs in HLA −ve plasma, HLA +ve PLTs in HLA +ve plasma, HLA −ve PLTs in HLA −ve plasma and HLA −ve PLTs in HLA +ve plasma. Samples from each PLT concentrate-mix were transferred to sterile non-treated culture plates and stored on a flatbed mixer at 37°C in an atmosphere of 5% CO2 in humidified air. HLA class I surface expression was tested daily during storage. The difference in % between pos PLTs in neg plasma and pos PLTs in pos plasma was in the range of 0.8 – 1.2 at 22°C and 0.8 – 3.3 at 37°C for HLA A2; 3.3 – 1.7 at 22°C and 3.5 – 0 at 37°C for HLA A9, and 3.9 – 1.9 at 22°C and 0 – 2.1 at 37°C for HLA B27. Percent-wise difference between neg PLTs in pos plasma and neg PLTs in neg plasma was in the range of 6.9 – 10 at 22°C and 7.7 – 12.5 at 37°C for HLA A2; 4.5 – 0 at 22°C and 13.6 – 6.5 at 37°C for HLA A9, and 5.3 – 5.3 at 22°C and 5.6 – 4.8 at 37°C for HLA B27. These results indicate that the amounts of eluted vs. adsorbed HLA class I antigens are negligible at both 22°C and 37°C. Hence, this method was applied in a clinical setting to study in vivo survival of transfused PLTs. A patient was transfused with PLTs of non-self HLA class I types and tracing and testing of the transfused PLTs were performed by daily measuring of HLA class I surface expression by multi-colour flow cytometry. PLTs were identified by light scatter properties and expression of CD41. The anti-HLA class I mAbs were used to distinguish transfused PLTs from autologous PLTs. The activation status of transfused PLTs was determined by using anti-CD63. PLT activation capacity was further determined by examining the expression of CD63 on different PLT populations before and after stimulation with thrombin receptor agonist peptide (SFLLRN). In a 52 years old patient with AML undergoing allogeneic stem cell transplantation early stem cell engraftment could be detected by following the PLT production (see figure). After the transplantation the number of autologous HLA A2 +ve PLTs decreased gradually. From day 8 till day 10 there was a 50% decrease in total PLT count, while the number of HLA A2 +ve PLTs was low but stable. From day 10 and onwards a gradual increase of HLA A2 +ve PLTs was seen independently of transfusion. These results were interpreted as engraftment from day 8. The standard criteria for stem cell engraftment - a neutrophile count of 〉 0, 1 × 109/L - occurred 5 days later in this patient. It was also found that the transfused PLTs in the patient's circulation were not activated, evaluated by CD63 expression, and that the residual activation capacity of the transfused PLTs were reduced compared with the capacity of the autologous PLTs (40% up regulation of CD63 vs. 70%; as a comparison there was a 90% up regulation of CD63 in a healthy individual). In conclusion, HLA class I typing by flow cytometry represents a powerful tool for studies of transfused PLTs. The method can 1) be used to study the survival of 3 different populations of transfused PLTs individually, 2) give early evidence of stem cell engraftment after allogeneic stem cell transplantation, 3) be used to assess in vivo activation of transfused PLTs and 4) be used for functional studies of transfused vs. autologous PLTs, which to our knowledge, is the first time this has been possible. Disclosures: No relevant conflicts of interest to declare.

Description: Introduction: Data on APCC´s effectiveness, safety and quality of life are relatively poor because of the rarity of patients with FVIII or FIX inhibitors, the small populations included in clinical trials and the relatively short follow-up available. The FEIBA-GO study was designed to capture long-term outcomes on effectiveness, safety and health-related quality of life (HR-QoL) in subjects receiving APCC in different settings in routine clinical practice. Primary objective is to describe the hemostatic effectiveness of APCC in different settings (prophylaxis and on demand, including patients on immune tolerance induction); most relevant secondary objectives aim at describing joint functionality outcomes, safety, HR-QoL, daily activity level, acute and chronic pain associated with hemophilia, as well as healthcare resources used. Methods: The study is a prospective, non-interventional, multicenter cohort study in patients with hemophilia A or B and high-responding inhibitors treated with APCC. A hundred subjects are targeted for enrollment; treatment regimens are at the discretion of the attending physicians in accordance with routine clinical practice, either on early, secondary or tertiary prophylaxis or on demand, including patients treated with APCC during immune tolerance induction. The observation period per subject will be 4 years. Results: As of June 1, 2016, 40 centres have been qualified in 14 countries and 16 centres have been initiated. 27 patients have been enrolled at 14 open sites in 7 countries. Demographic data are available for the 27 patients enrolled so far and are presented for the first time. All patients have severe hemophilia A: 23 are caucasian, 1 african (3 missing). At the enrolment, 18 of them were on prophylaxis and 6 treated on demand (3 missing). Overall median age is 19 years (min-max: 3-71), 17.5 years in patients on prophylaxis (min-max: 3-71) and 39.5 years in patients on demand (min-max: 22-65). Overall median inhibitor titer at enrolment was 8 BU (min-max: 1-2410), 8 BU for prophylaxis (min-max: 1-92) and 12 BU in patients on demand (min-max: 3-35). Nijmegen modified Bethesda assay was used in 18 centres, while 4 used non-modified Nijmegen Bethesda assay (5 missing). Six subjects (3 on prophylaxis, 2 on demand and 1 unknown) have been reported to have overall 13 target joints. Assessment for acute pain was performed in 12 patients and for chronic pain in 9 patients. Two of 12 patients assessed reported acute pain (both on demand). Two of the 9 patients in whom the assessment was performed reported chronic pain (treatment regimen missing). For one patient, information is not available and for another one it has been reported that pain assessment is not routine examination. Gilbert Score was assessed in 6 patients at screening. Discussion/Conclusion: This study will further enhance the information on long-term effectiveness, HR-QoL and safety of APCC across and beyond Europe in the real world on hemophilia A and B patients with high-responding inhibitors under a variety of prescribing regimens in routine clinical practice. Disclosures Cid: Baxalta Innovations GmbH, now part of Shire: Other: Investigator Clinical Studies. Escuriola:Baxalta, now part of Shire: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Investigator Clinical Studies, Research Funding; Bayer: Consultancy, Honoraria, Research Funding; Biotest: Consultancy, Honoraria, Research Funding; CSL Behring: Consultancy, Honoraria, Research Funding; Grifols: Consultancy, Honoraria, Research Funding; Octapharma: Consultancy, Honoraria, Research Funding; NovoNordisk: Consultancy, Honoraria, Research Funding. Hermans:Baxalta, now part of Shire: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Investigator Clinical Studies. Holme:Baxalta, now part of Shire: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Investigator Clinical Studies. Negrier:LFB: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees, Other: Travel support; SOBI: Membership on an entity's Board of Directors or advisory committees; Octapharma: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Baxter: Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding; Alnylam: Research Funding; CSL Behring: Membership on an entity's Board of Directors or advisory committees, Research Funding; NovoNordisk: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding. Rangarajan:Baxter: Research Funding; Grifols: Consultancy, Research Funding; Biogen: Consultancy; Pfizer: Research Funding; Baxalta, now part of Shire: Other: Investigator Clinical Studies, Research Funding; Novo Nordisk: Research Funding; Biotest: Research Funding. Rocino:Baxalta, now part of Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Investigator Clinical Studies; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees; NovoNordisk: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; CSL Behring: Consultancy, Honoraria; Kedrion: Consultancy, Honoraria; Sobi: Consultancy, Honoraria. Windyga:Octapharma: Consultancy, Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding, Speakers Bureau; Alexion: Other: Speaker's honorarium; Biogen: Consultancy, Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding, Speakers Bureau; Sanofi: Consultancy, Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding, Speakers Bureau; CSL Behring: Consultancy, Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding, Speakers Bureau; Aspen: Consultancy, Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding, Speakers Bureau; Nordisk: Consultancy, Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding, Speakers Bureau; Baxalta, now part of Shire: Consultancy, Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Investigator Clinical Studies, Patents & Royalties, Research Funding, Speakers Bureau. Gringeri:Shire: Employment, Equity Ownership. Crea:Shire: Employment, Equity Ownership.

Description: Background: Hemophilia carriers report abnormal bleeding, even when factor VIII or IX levels are normal. Information comparing bleeding events between carriers and women with other inherited bleeding disorders is lacking. Purpose: The purpose of our study was to characterize bleeding in hemophilia carriers using the International Society on Thrombosis and Hemostasis Bleeding Assessment Tool (ISTH-BAT) and to compare it with bleeding in normal controls, women with Type 1 VWD and Type 3 VWD obligate carriers (OC). Method: This was a prospective, observational, cross-sectional study performed by members of GEHEP (Global Emerging HEmostasis Panel). Study participants were recruited from GEHEP members' clinics in North America (Kingston, Canada, Detroit and Philadelphia, USA), Europe (Malaga, Spain; Milan, Italy; Munich, Germany; Oslo, Norway) and South Africa (Johannesburg). Potential participants were identified through local patient databases and approached during clinic visits. All participants signed informed consent. Hemophilia carriers were defined by a documented FVIII or FIX mutation and/or by an appropriate family history (daughter of a man with hemophilia or mother of two sons with hemophilia or mother of one son with hemophilia with at least one other affected male relative). Demographic information was collected using a CRF and the ISTH-BAT was completed for each participant by study personnel. Existing ISTH-BAT data for women with Type 1 VWD, Type 3 VWD OC and age-matched female controls were used for comparison. Results: A total of 329 participants were included in this study; 168 hemophilia carriers, 83 women with Type 1 VWD, 32 Type 3 VWD OC and 46 female normal controls. Hemophilia carriers and normal controls were similar in age (40.1 vs 41.6, p=0.445). The mean overall ISTH-BAT bleeding score (BS) was significantly higher in carriers than in controls (5.7 vs 2.48, p Type 3 VWD OC 〉 controls. Additional research into the underlying pathophysiology of this abnormal bleeding is a critical next step in understanding and determining how to appropriately manage these patients. Disclosures Bidlingmaier: Novo Nordisk: Honoraria; Sobi: Honoraria; Pfizer: Honoraria; Biotest: Honoraria; Baxalta: Honoraria; Bayer: Honoraria; CSL Behring: Honoraria, Research Funding. Mingot-Castellano:Amgen: Consultancy; Pfizer: Consultancy; Novo Nordisk: Consultancy, Research Funding; Baxalta: Consultancy, Research Funding; Novartis: Consultancy; Bayer: Consultancy, Research Funding. Chitlur:Novo Nordisk: Consultancy; Baxalta: Honoraria; Bayer: Honoraria; Biogen-Idec: Honoraria; Pfizer: Honoraria. Fogarty:Bayer Healthcare: Membership on an entity's Board of Directors or advisory committees, Research Funding; Baxter/Baxalta: Membership on an entity's Board of Directors or advisory committees, Research Funding; Biogen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Chugai: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; Pfizer: Employment, Membership on an entity's Board of Directors or advisory committees, Research Funding; Spark Therapeutics: Research Funding. Cuker:T2 Biosystems: Research Funding; Genzyme: Consultancy; Biogen-Idec: Consultancy, Research Funding; Amgen: Consultancy; Stago: Consultancy. Mancuso:Bayer Healthcare: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Baxalta: Consultancy, Speakers Bureau; CSL Behring: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novo Nordisk: Consultancy, Speakers Bureau; Sobi/Biogen Idec: Consultancy, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kedrion: Consultancy. Holme:Baxalta, now part of Shire: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Investigator Clinical Studies. Mathew:Bayer: Employment. James:CSL Behring: Research Funding; Octapharma: Research Funding; Biogen: Consultancy; Basalt: Consultancy; Bayer: Research Funding.

Description: Background: It has been speculated that more episodes of hematuria in severe hemophilia might be a sign of increased renal disease, and that HIV or HCV infections might have a detrimental effect on the kidney*. Only a few comprehensive reports on the extent of renal disease in hemophilia have been published to date¨. Aims: A cross-sectional study in Europe was conducted by the ADVANCE Working Group to investigate the extent of renal disease, creatinine clearance, hematuria episodes and Cystatin C values in a cohort of patients aged over 40 years with severe (5-40% FVIII) hemophilia. Methods: Patient data from 16 centers were analyzed to describe the rate of renal disease as assessed by the treating physician, and also measured by serum creatinine, age adjusted creatinine clearance (CrCl), and available Cystatin C values at a single time point in a representative selection of patients; providing that IRB approval and patient consent was available. Results: 509 patients with hemophilia were recruited (88% hemophilia A, 12% hemophilia B; 58% severe; 11% moderate, 31% mild). 35% of the total and 55% of the severe group was on prophylaxis. Median age was 52 years (range 35-98 years), 19% were HIV positive and the majority on HAART treatment. 71% were HCV seropositive, of whom 11% had reached natural clearance and 18.8% a persistent response. Significantly lower median BMI (25.3 vs. 26 kg/m²; P70 years old, p=0.03*). Median creatinine clearance values (CrCl) were calculated from the serum creatinine values according to Cockroft Gault formula, and were significantly higher in severe hemophilia than mild (eGFR 116 ml/min vs. 106 ml/min; p=0.003). Cystatin C values were only measured for 23.6% of patients with more data available for severe/moderate than mild hemophilia (30% vs. 10%), but the values (Median=0.9, IQR: 0.78-1.07) were no different to normal in these age groups€. 54% had a history of macroscopic hematuria, with significantly more patients with hematuria history in severe disease (70% in severe vs. 27% in mild). The CrCl and renal disease status did not correlate with severity or number of macroscopic hematuria episodes (p=0.60). Conclusion: Renal disease in hemophilia significantly increases with age but the rate does not differ between severe and mild hemophilia. Hematuria episodes do not appear to indicate or affect renal status in the majority$. HCV and HIV status looks to have an effect on BMI and might explain why better CrCl is shown in severe patients with hemophilia compared to mild. Acknowledgment: The ADVANCE Working Group is supported by a scientific grant from Bayer HealthCare AG. Disclosures Klamroth: Bayer, Baxter, CSL Behring, Pfizer, Novo Nordisk, and Octapharma: Honoraria, Research Funding, Speakers Bureau; Biogen and SOBI: Honoraria, Speakers Bureau.

Description: Immune thrombocytopenia (ITP) is an autoimmune disease characterized by immune mediated platelet destruction causing thrombocytopenia and increase risk of bleeding. Treatment is indicated in patients who present with bleeding or are at risk of bleeding. Corticosteroids (CS) are the main first-line treatment in adult patients, but since not all patients achieve adequate response to CS, most patients require a second line therapy. Rituximab is one of the most widely used second line therapies; its advantages include the ability to induce relatively long lasting remissions after 2-4 infusions and its favorable safety profile. The RITP study was a randomized placebo-controlled trial in which ITP patients who failed to achieve adequate response to CS were randomized to receive rituximab or placebo. The study outcomes were treatment failure (splenectomy or meeting criteria for splenectomy), response rates and duration of response during an 18-month follow-up period. Apart from a longer duration of response in the rituximab arm, the study showed no significant differences in the other outcomes (Ghanima et al. Lancet 2015; 385: 1653-61). The use of stable dose of CS was allowed during the study. This report represents a post-hoc analysis of the RITP trail, restricting the population to those who did not receive any CS during the study, until relapse or treatment failure in the two arms. By this we aimed to eliminate the possible interference resulting from concomitant use of CS on the effect and safety of rituximab and placebo. For effect, we estimated the duration of response, splenectomy rates, platelet counts, and time to bleeding and for safety we estimated time to infection episodes in both arms. We included patients who did not receive CS before treatment failure or relapse or until the end the of the study, if none of the endpoints was achieved. The duration of response was estimated from time of achieving response to relapse (platelet count