bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patern of Acquired Hemophilia in Saudi Arabia
Authors: Al-Momen Abdul Kareem M , Owaidah Tarek M , Sayed Zaidi Z , Ahmed Mady F , Amr Hanbali , Saud Balelah , Shahid Iqbal , Imran Tailor , Rehman Zaidi 
Published: October 2019

Abstract
Background: Acquired Hemophilia (AH) is a rare bleeding disorder that develops secondary to an autoantibody against Factor VIII in persons who are not known to have any previous bleeding disorder. Aim: The aimof this retrospective case review is to explore the pattern of confirmed cases of AH that were managed in Saudi Arabia over a 5 years' period.
Patients and Methods: We reviewed the charts of documented cases of AH that were managed in 5 Tertiary Hospitals (4 in Riyadh and 1 in Al Madinah Al Monawarah) from 2010 to 2014. All cases underwent medical history, physical examination, laboratory tests including complete blood count, activated partial thromboplastin time (PTT), mixing studies, factor VIII level, and Factor VIII Inhibitor titer. All patients received standard treatment.
Results: We found 19 cases, but we could obtain data only for 13 cases, 4 males and 9 females, median age was 30 years (range 20-85). Risk factors were pregnancy in 5, Autoimmune disease in 2, Cancer in 1, Clopedogril in 1 and 4 were idiopathic. All cases presented with various degrees of bruises. in addition, 4 cases presented with menorrhagia, 4 cases with soft tissue hematomas, and 2 cases with gross hematuria. All cases had prolonged aPTT, which was only partially corrected with mixing studies, very low factor VIII level (median 1, range <1-12.5%), and high factor VIII inhibitor titer (median 22.4 BU, range 3.5-1932). Treatment included steroids, cyclophosphamide, immunoglobulins and Rituximab. There were 9 remissions (with 2 relapses, which responded to treatment), 2 partial responses, and 2 deaths due to massive blood loss (Hematuria).
Discussion: Our case series indicates only severe AH, because many milder cases are underdiagnosed or misdiagnosed. Although the number of our cases are small, they indicate a different pattern from the published studies, because of younger age group and female predominance.
Conclusion: Our case series indicates that most of our cases are young adults, with female predominance. A comprehensive review of cases from other hospitals is underway

Disclosures
No relevant conflicts of interest to declare.
Characterization of Two Cases of Congenital Thrombotic Thrombocytopenic Purpura (TTP)
Authors: Bai Xia , Su JIan , Cao Lijuan , Ruan Changgeng 
Published: October 2019

Abstract
Introduction: Congenital thrombotic thrombocytopenic purpura (TTP) is characterized by disseminated thrombus due to the mutations of ADAMTS13, which cleaves its substrate von Willebrand factor(VWF) in shear-induced unfolding condition. Most of the congenital TTP we found is woman with pregnancy. Here, we characterize two children suspected with congenital TTP.
Methods:ADAMTS13 activities were analyzed by residual collagen binding assay (R-CBA) plus FRET-VWF substrate. And the inhibitors of ADAMTS13 were analyzed by 9:1 mixture of patient and pooled normal plasma followed by R-CBA. The secretion of recombinant ADAMTS13 mutants was studied.
Results: Two children, one aged four months and the other aged three years old, were diagnosed with congenital TTP because their ADAMTS13 activities were less than 5% (both FRET-VWF and R-CBA), and there are short of ADAMTS13 inhibitors. The following mutations were found: Q1385P, Y177C, C522R. In addition to the previously reported mutation of Y177C, the two novel mutations (Q1385P and C522R) failed to secrete from the HEK293 cells.
Conclusion: Two children with congenital TTP were determined thanks to screening of ADAMTS13 activity and its corresponding inhibitor assays, and it seems that congenital TTP could occur in different ages although most of congenital TTP we found were women with pregnancy.

Disclosures
No relevant conflicts of interest to declare.
Safety and Feasibility of Treatment with Rivaroxaban in Children for Non-Routine Indications: A Case Series Analysis
Authors: Dickerson Kathryn E. , Sarode Ravi , Zia Ayesha 
Published: October 2019

Background. Anticoagulation therapy is the cornerstone of acute treatment of venous thromboembolism (VTE) and for prevention of recurrent VTE. The need for anticoagulation is increasing in children, largely in part due to increasing VTE rates. Conventional anticoagulants, including heparin, low-molecular weight heparins (LMWH), Fondaparinux, and vitamin K antagonists (VKA) are widely used in children but have limitations. Standard of care management with these agents is plagued with the trade-off between daily or twice daily injections or frequent monitoring of therapeutic effect. The advent of direct oral anticoagulants (DOACs) have catalyzed significant changes in the therapeutic landscape of VTE management. DOACs have been evaluated for safety and efficacy in large, randomized controlled trials in the treatment and prevention of VTE in adults, with results that are comparable to conventional therapy. None of the current DOACs have FDA-approved indications and dosing in children yet. Off-label use of these agents is largely based on adult data and doses, and is increasing at many Children's Hospitals across US. Rivaroxaban, a DOAC, is a factor Xa inhibitor with predictable pharmacokinetic and pharmacodynamics properties.
Methods. We describe a case series of 8 unique pediatric cases, treated with Rivaroxaban, for a variety of non-routine indications, due either to adverse effects, intolerability of LMWH or VKA or the need for ongoing, long term anticoagulation. Rivaroxaban was started after informed consent and assent from parents or patients respectively, and was initiated at a fixed dose but titrated to a final dose after monitoring of trough and peak Rivaroxaban levels (Aniara, West Chester,OH, USA).
Results. The mean age of patients in this case series is 14 years (median: 16, range 3-17) (see Table). The most common indication to use Rivaroxaban was the need for long term anticoagulation after having completed therapeutic anticoagulation, except in two patients, one of whom developed warfarin skin necrosis due to protein C deficiency and another with heparin induced thrombocytopenia. Only two patients needed dose adjustments to achieve target trough and peak drug levels. The mean duration of follow-up is 9 months (median= 5.5; range 3-24) (see Table) at this time. None of the patients developed recurrent VTE while on Rivaroxaban. A soft tissue traumatic bleed occurred in one patient which was treated with holding off the drug for 48 hours. No other bleeding complications were observed.
Conclusions. Clinical application of DOACs in a real world clinical setting, including strong thrombophilia and malignancy, results in treatment profile of high efficacy and safety in children; however, larger studies are needed to validate these findings.

Disclosures
Sarode: CSL Behring: Consultancy, Honoraria.
A Spin-Off in Non Valvular Atrial Fibrilation (NVAF) and Cancer : Doacs As a Safe and Effective Alternative to the Convencional Avks
Authors: Johansson Erik , Olivera Pável , Canals Tania , Bosch Francesc , Pons Verónica , Santamaría Amparo , Cortina Vicente 
Published: October 2019

Abstract
Introduction:
The anticoagulation is common in patients with cancer such as treatment or prevention of venous thromboembolic events (VTE) or atrial fibrillation (AF). The evidence for the effectiveness and safety of the direct oral anticoagulants (DOACs) in those clinical setting are sparse, even more in AF patients.
Aim: to analyze the effectiveness and safety of the DOACs, and other clinical aspects of patients with active cancer in the treatment of atrial fibrillation in daily clinical practice.
Methods:
Between Nov 2011 and May 2016 we had included consecutively adult patients with AF who initiated DOACs treatment. We selected patients with active cancer. Follow-up (FU) was an outpatient visits each 3 months and thereafter effectiveness, safety and other related to treatment data were collected. All bleeds were classified using the ISTH criteria.
Results:
900 patients were included in our register where 6.1% (n=55) had an active cancer. Median age was 78 years (range 57-91) and 45.5% were women and 55.5% men. The median of creatinina clearance 59 ml/min (range 30-101). The distribution for treatment groups was: dabigatran 16.4% (n=9) with 24 months or days FU, rivaroxaban 50% (n=28) with 8 months and apixaban 32.7%(n=18) with 4 months. Ischemic strokes occurred in 16.4% of the patients with cancer (n=9).During FU, 10 patients presented bleeding complications (7.3 % minor,7.3% non-major clinically relevant and 3.6 % major bleeding according to ISTH definition).The mucocutaneous bleeding was the most common site of bleeding (30% of total bleeding) in the 5.5% drugs. In the clinical FU we observed 2 deaths, related to progression of the underlying disease. The DOACs discontinuation occurred in 16.4% (n=9) due to presence of bleeding events, hematological toxicity in chemotherapy; and worsening functio renal. The DOAC treatment was maintained concomitant with antineoplastic therapy in 83.6% (n=46) without associated complications.
Conclusion:
DOACs in active cancer-patients patients showed a good effectiveness and safety and they can be a great option in the treatment of NVAF, especially in those cases with unestable INR ranges.. There is an urgent need for more clinical studies in cancer patients treated with DOACs that can be candidates to these, in terms to offer them a better therapeutic options.

Disclosures
Bosch: Roche: Consultancy, Honoraria, Research Funding; Gilead Sciences: Membership on an entity's Board of Directors or advisory committees.
Decrease of Aggregation By Platelet Impedance Aggregometry ( MULTIPLATE ) in Patients Treated with Dabigatran
Authors: Cabañas Valentin , Cerezo-Manchado Juan Jose , Garcia-Candel Faustino , Salido Eduardo , Lopez-Perez Raul , Garcia-Hernandez Ana , Berenguer Merecedes , Labbadia Francesca , Blanquer Blanquer Miguel , Moraleda Jose Maria 
Published: October 2019

Abstract
Introduction: Dabigatran is a direct oral anticoagulant (DOAC) that has been proved effective and safe in preventing thromboembolic events experienced by patients with non-valvular atrial fibrillation (AF). This drug acts directly inhibiting thrombin and particularly affects the intrinsic and the final coagulation pathways. Thrombin is a platelet agonist therefore dabigatran could be involved in altering the aggregation. However, it is not well known whether they modify the platelet function. We conducted an initial study in our hospital to assess platelet aggregation in patients treated with dabigatran.
Methods: An observational study was conducted in 17 randomly selected patients who had started dabigatran in the last year in our center. The results were compared with 8 healthy platelet donors randomly selected from our database. Platelet aggregation was quantified in patients and controls using MEA (Multiplate, Roche Diagnostics, Switzerland). The indication and dosing of dabigatran was performed as clinically indicated. The main variables investigated were: aggregation time with four agonists: thrombin, ADP, collagen, ristocetin, APTT, INR addition, D Dimer, kidney and liver function and the usual demographic parameters. Statistical analysis were performed using SPSS 21.0 (SPSS Inc., Chicago, IL).
Results: All patients had AF as an indication for treatment with dabigatran. Dabigatran doses were 110 mg in 7 patients (41%) and 150 mg in 10 patients (58%). No patient was on any antiplatelet agent. Platelet aggregation induced by TRAP measured by MEA was not significantly different in patients compared to controls: 121 RI (94-127) vs. RI 122 (108-137) units (p = 0.711). Aggregation using collagen and ristocetin as agonists was significantly decreased compared to that of controls: RI 48 (32-63) vs. 83 RI (69-110) (p = 0.05) and 76 RI (71-32) vs. 120 RI (97-142) units (p <0.01). There were no differences in the aggregation depending on the dose of dabigatran. Conclusion: Despite the limitations of the study we observed a change in the aggregation of patients treated with dabigatran measured by MEA, compared with healthy controls. Contrary to what one might expect, it was not dependent on the thrombin pathway unless the ristocetin and collagen agonists. These findings must be confirmed in more powerful studies designed for this purpose because others studies, with the same characteristics than our work, have shown TRAP-induced platelet aggregation enhance in patients treated with dabigatran.1
1 TRAP-induced platelet aggregation is enhanced in cardiovascular patients receiving dabigatran. Christoph B. Olivier et al. Thrombosis Research Thromb Res. 2016 Feb;138:63-8

Disclosures
Blanquer Blanquer: Pfizer: Research Funding.
Blood Donation May Not Reduce Risk of Testosterone-Induced Polycythemia
Authors: Chin-Yee Benjamin Hull , Lazo-Langner Alejandro , Foster Terrie , Hsia Cyrus C. , Chin-Yee Ian 
Published: October 2019

Abstract
Background:Polycythemia is the most common adverse effect of testosterone replacement therapy (TRT) and may predispose patients to adverse vascular events. Current Canadian guidelines recommend regular laboratory monitoring and discontinuing TRT or reducing the dose if the hematocrit exceeds 54% (hemoglobin ≥180 g/L). This threshold has been interpreted by some physicians and patients to indicate the need for phlebotomy or blood donation while on TRT.
Study Design and Methods: We reviewed all male blood donors in Southwestern Ontario at Canadian Blood Services from December 2013 to March 2016 who self-identified or were found on donor screening to be using TRT in any form. Hemoglobin concentration was measured at the time of donation or clinic visit and with each subsequent appointment in repeat donors.
Results:We report a case series of 39 patients on TRT who presented for blood donation over a two-year period. The mean hemoglobin at all donor clinic visits was 173 g/L (range 134-205 g/L, n = 108). Hemoglobin concentrations of ≥180 g/L (calculated hematocrit ≥54%) were measured at 25% of appointments. Of the 27 repeat donors, 12 (44%) had persistently elevated hemoglobin levels (≥180 g/L) at subsequent donations.
Conclusions: Hemoglobin concentrations were elevated in blood donors on TRT, with a significant number above levels recommended by current guidelines. These data also suggest that repeat blood donation was insufficient to maintain hematocrit below 54%. Our findings raise concerns about persistent risk of vascular events in these donors, particularly when coupled with the misperception by patients and health care providers that donation has abrogated the risks of TRT-induced polycythemia.

Disclosures
No relevant conflicts of interest to declare.
Audit of Red Cell Transfusions in the Neonatal Intensive Care Unit, Rotunda Hospital 2011-2015
Authors: Enright Siobhan , Ní Áinle Fionnuala , Foran Adrienne 
Published: October 2019

Abstract
Introduction/Background
Neonates are an intensively transfused group of vulnerable patients. Neonatal transfusion practice and general care has evolved over recent years, including the introduction of pedi-packs to limit donor exposure, and it remains important to audit practice. Inappropriate transfusions expose babies to potential adverse effects of transfusion. A national audit performed in the UK in 2010 concluded that there is a lack of evidence to back many of the existing recommendations for neonatal transfusion.
We undertook a prospective audit in order to review 5 years of transfusion practice in a tertiary NICU. Our current neonatal transfusion guidelines are based upon internationally published guidelines.
Aims & Objectives:
To determine the number of babies transfused, whether transfusions were adherent to local guidelines, to identify areas requiring improvement and to determine whether continuous auditing and feedback to clinicians improves practice
Methodology/Interventions This was a prospective audit conducted over a 5 year period. Data were prospectively and retrospectively retrieved from patient charts and electronic databases. Data were stored in a password-protected excel spreadsheet created on a secure hospital network.
Results and Discussion A total of 557 babies were transfused with red cells during the period 2011 -2015, representing 7-12% of babies admitted to NICU. The median number of transfusions decreased in babies of all birth weight categories between 2011-2015. The biggest change was in babies <750g, where median donor exposure was reduced from 2 to 1 during this time. The overall percentage of babies admitted to NICU requiring a blood transfusion reduced from 12% to 7%. The most significant reduction was seen in babies ≥1500g with a reduction from 4% in 2011 to 2% in 2015.
Conclusions Auditing of neonatal transfusion especially in the area of pedi-pack top up transfusions highlighted specific areas where improvements could be made. This includes adherence to guidelines, consultant-led decision to transfuse (when time permits), and on-going audit and feedback to clinicians. These measures along with a multi-disciplinary approach to blood management have seen an overall reduction in percentage of babies being transfused without compromising the well-being of the baby. This has led to a reduction of donor exposure to the baby and a reduction in the cost and workload across all disciplines of staff associated with blood transfusion leading to an overall improvement to patient safety and quality of care. Despite this, the transfusion rate in babies of < 1000g remains the highest however this would be expected given the overall clinical needs of babies in this birth weight category.
Figure 1 Figure 1. Figure 2 Figure 2.

Disclosures
Ní Áinle: Actelion UK: Research Funding.
Suppression of Mir-708 Promotes DKK3 to Inhibit Wnt/β-Catenin Signaling Pathway in Adult B-ALL
Authors: Zhang Yingjie , Li Huibo , Cao Rongyi , Sun Lili , Wang Yan , Fan Shengjin , Zhao Yanqiu , Kong Desheng , Cui Lin , Lin Leilei , Wang Ke , Wang Chen , Li Yinghua , Zhou Jin 
Published: October 2019

Abstract
Dickkopf-3 (DKK-3) is a Wnt signaling antagonist, and DKK3 inactivation is associated with poor prognosis in various solid tumors and hematologic malignancies. Epigenetic hypermethylation has been implicated in downregulation of DKK3, but other regulatory mechanisms remain to be investigated. In this study, we examined DKK3 expression and the role of microRNA in the regulation of DKK3 in adult B-ALL. Our results showed low levels of DKK3 expression in Nalm-6 and BALL-1 cell lines, and leukemia cells from adult B-ALL patients. DKK3 expression was remarkably lower in the initial diagnosis and relapse samples than in the matched samples during remission. In addition to hypermethylation, low levels of DKK3 were associated with high expression of miR-708. This finding was similar to that in childhood ALL. The miR-708 was predicted to bind to the 3'-UTR of DKK3. By using miR-708 mimics, we found that miR-708 targets DKK3 to promote B-ALL cell proliferation through cell cycle promotion and apoptosis inhibition. The treatment with 5-aza-2'-deoxycytidine significantly increased DKK3 and decreased p-GSK3β, cyclin D1 and nuclear and cytoplasmic β-catenin protein expression. A synergistic effect was seen when the miR-708 inhibitor and 5-aza were used simultaneously. Although miR-708 was reported to either promote or suppress tumorigenecity in some solid tumors, our findings indicate that suppression of miR-708 increases DKK3 expression to inhibit the Wnt/β- catenin signaling pathway in B-ALL.

Disclosures
No relevant conflicts of interest to declare.
The Level of Histone Deacetylase 7 in Pediatric ALL and Its Effect on Survival
Authors: Hou Bei , Zheng Huyong 
Published: October 2019

Abstract
Background
Leukemia is the most common pediatric malignancy and a major cause of mortality and morbidity in children. Nearly 15,000 children are newly diagnosed with leukemia in China each year and among them, acute lymphoblastic leukemia (ALL) accounts for more than 75%. Altered expression of histone deacetylases (HDACs) is a common feature in several human malignancies and may represent an interesting target for cancer treatment . With increasing focus on precision medicine, HDACs have emerged as promising therapeutic target in pediatric ALL.
Methods
We detect the histone deacetylase 7(HDAC7) expression in the bone marrow samples of 254 children with newly diagnosed acute lymphoblastic leukemia (ALL) at Hematology Oncology Center of Beijing Children`s Hospital from January 2010 to the end of 2012 via qRT-PCR using the TaqMan gene expression probes. 3 patients that have been completely remission for 3 years are used as normal control. We find out that the expression levels of HDAC7 are associated with the unfavorable events (such as induction failure, relapse and/or death due to any cause ) occurence rates and 5-EFS.
Results
Here we find that the HDAC7 expression levels are associated with the unfavorable events occurence rates and 5-EFS. We find that in the intermediate risk group of 157 patients, the patients who have lower level of HDAC7 expression have higher unfavorable event occurence rates than the higher expression of HDAC7 group (p=0.001). The group of higher HDAC7 expression have higher 5-EFS than the lower group in both the intermediate risk group(p=0.001) and the T-ALL group(n=18).
Conclusion
We conclude that HDAC7 has a potent anti-oncogenic effect on specific pediatric B-cell leukemia, indicating that its deregulation may contribute to the pathogenesis of the disease.

Disclosures
No relevant conflicts of interest to declare.
Potent Anti-Leukemic Effects of Small Molecule ONC212, a Member of the Imipridone Class of Anti-Cancer Compounds
Authors: Prabhu Varun V , Tarapore Rohinton S , Garnett Mathew J , McDermott Ultan , Benes Cyril H , Wagner Jessica M , El-Deiry Wafik S. , Stogniew Martin , Oster Wolfgang , Allen Joshua E 
Published: October 2019

Abstract
ONC201, the founding member of the imipridone class of anti-cancer compounds, is a highly selective small molecule GPCR antagonist that is in Phase I/II advanced cancer clinical trials. In this study, we evaluated the anti-cancer effects of ONC212, an ONC201 analogue that possess the same unique core chemical structure shared by imipridones.
The in vitro efficacy of ONC212 was assessed in the Genomics of Drug Sensitivity in Cancer collection of cell lines (>1,000 cell lines). Cell viability assays were performed to generate dose responses curves at concentrations from 78nM upto 20uM and at 72 hours post-treatment. ONC212 was broadly efficacious across most solid tumors and hematological malignancies in the low nanomolar range. Ranking the ONC212 sensitivity dataset revealed that leukemia is the most responsive tumor type based on completeness of response (area under the dose-response curve, AUC).
ONC212 was tested in 65 leukemia cell lines in this study that is comprised of acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML) and hairy cell leukemia. ONC212 demonstrated broad spectrum anti-leukemic activity and was equally efficacious across all leukemia subtypes tested, in terms of AUC. Most cell lines (63/65) were responsive to ONC212 with GI50 ranging from <78nM to 312nM. Within ALL, both B-cell and T-cell ALL were highly sensitive to ONC212. ONC212 reduced cell viability in AML independent of complex karyotypes that are associated with poor clinical prognoses.
Thus, ONC212 possesses robust anti-leukemic activity irrespective of subtype and provides further validation of the anti-cancer efficacy of the novel imipridone class of small molecules.

Disclosures
Prabhu: Oncoceutics: Employment. Tarapore:Oncoceutics: Employment, Equity Ownership. El-Deiry:Oncoceutics: Equity Ownership. Stogniew:Oncoceutics Inc.: Employment, Equity Ownership. Oster:Oncoceutics: Employment, Equity Ownership. Allen:Oncoceutics: Employment, Equity Ownership.