bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective Evaluation of Hemostatic Abnormalities in Overt DIC Due to Various Underlying Diseases
Authors: Wada Hideo , Hatada Tsuyoshi , Kawasugi Kazuo , Nobori Tsutomu 
Published: October 2019

Abstract
Abstract 4652

[Introduction]
Disseminated intravascular coagulation (DIC) is often found in patients with infections, leukemia, solid tumors, trauma, aneurysms or obstetricdiseases. The causes of DIC associated with leukemia are considered to be an elevated expression of tissue factor, tissue type plasminogen activator or anexin II in leukemic cells. The factors thought to be responsible for DIC associated with sepsis are an elevated inflammatory response, including an increased production of inflammatory cytokines.

[Materials and Methods]
In this study, 692 patients with suspected DIC were prospectively evaluated for various types of underlying diseases using the DIC diagnostic criteria established by International Society of Thrombosis and Haemostasis (ISTH) and Japanese Ministry Health Labor and Welfare (JMHLW), and the usefulness of hemostatic markers were examined for each patient with DIC due to various underlying diseases.

[Results]
The main underlying disease of DIC was infectious diseases, hematologic malignancies, and solid tumors, and a high resolution rate from DIC was observed in obstetric diseases and hematologic malignancies. The diagnosis of DIC was related to a poor outcome in trauma/burn victims and those with infectious disease. In the main underlying disease, it is suggested that DIC would be excluded in patients with hematologic malignancies or solid tumors with a platelet count of more than 1×108/ml and in the patients with fibrinogen and fibrin degradation products (FDP) of less than 10 mg/L, and fibrinogen of less than 100 mg/dl, suggesting the presence of DIC. The prothrombin time was a sensitive marker, but fibrinogen levels were not sensitive for DIC due to infectious diseases. The plasmin plasmin inhibitor complex in hematologic malignancy, and soluble fibrin monomer complex, antithrombin and thrombomodulin in patients with infectious disease, were sensitive markers for the diagnosis of DIC.

[Discussion and conclusion]
Although hemostatic markers were useful for the diagnosis of DIC, the usefulness varied depending on the different underlying diseases. The global coagulation tests are therefore considered to be useful for the diagnosis of DIC, and hemostatic molecular markers are useful for examining the pathophysiology of patients with DIC.

Disclosures:
No relevant conflicts of interest to declare.
Importance of Individualized Replacement of Factor VIII Concentrate According to Recovery Test in Hemophilia A Patient During Surgery
Authors: Shim Ye Jee , Choi Yong-Mook , KIm Ji Yoon , Lee Kun Soo 
Published: October 2019

Abstract
Abstract 4654

Purpose:
There is a common guideline for surgery in hemophilia A patients - to maintain their factor VIII (FVIII) levels over 100% during and 24 hours after operation by infusion of FVIII concentrates. However their responses to coagulation factors are very different from each other even with the lack of inhibitor. Thus we demonstrated the correlation between individual FVIII recovery and prognosis after surgery.

Methods:
We reviewed the operation cases in hemophilia A patients who had recovery tests before surgery in Kyungpook National University Hospital from January 2001 to July 2011. The blood sample for recovery test was acquired at 15 minutes after initial infusion of FVIII concentrate from the opposite arm. The patients with inhibitors were excluded. The average hospitalization period and consumption of FVIII concentrates were analyzed.

Results:
A total 24 surgery cases in 16 hemophilia A patients were reviewed. They were divided into 3 groups; A (recovery/expected FVIII > 0.8), B (recovery/expected FVIII < 0.8, but they were managed by immediate additional replacement of FVIII concentrates), and C (recovery/expected FVIII < 0.8 and the extra supplementations of coagulation factors were delayed over 3 days). Type of operation included neurosurgeries (craniotomy/removal of hematoma 3, ventriculo-peritoneal shunt 2, ventriculostomy 1), orthopedic procedures (arthroplasty 4, open reduction/internal fixation 3, bone graft 1, drilling of bone 1), and gastrointestinal operations (subtotal gastrectomy 2, appendectomy 2, hemorrhoidectomy 2, rectosigmoidectomy 1, cholecystectomy 1, herniorrhaphy 1). The total consumption of coagulation factors and the dose per body weight were lower in group A compared with B and C (respectively p=0.028 and p=0.003, CI 95%). However the hospitalization periods were not different between group A and B (p=0.956, CI 95%). And in group B, the hospitalization period, total consumption of coagulation factors, and the dose per body weight were all lower than C (respectively p=020, p=023, and p=048, CI 95%). No complication was noted in group A and B while 2 cases of hematoma infection were developed in group C.

Conclusion:
The low FVIII recovery under 80% of expected may contribute higher consumption of coagulation factors after surgery in hemophilia A patients. However if the immediate supplemental FVIII replacement was performed, the medical expense would be conserved without complication. Thus the individualized replacement of FVIII concentrates according to the recovery test is very important for hemophilia A patients who need operation.

Disclosures:
No relevant conflicts of interest to declare.
Role of Inherited Bleeding Disorders in Women with Pregnancy Loss
Authors: Krause Manuela , Pillitteri Daniele , Pilgrimm Ann-Kathrin , Scholz Thomas , Schwerdtfeger Rainer , Kirchmaier Carl 
Published: October 2019

Abstract
Abstract 4657

Introduction:
Pregnancy is a hypercoagulable state, and thromboembolism is the leading cause of antepartum and postpartum maternal mortality. Women with thrombophilic mutations (factor V leiden, prothrombin, and MTHFR) and inherited bleeding disorders, such as deficiency of factor XIII and fibrinogen, have been shown to be at increased risk of pregnancy loss. However, the risk of miscarriage in women with other inherited bleeding disorders has been discussed controversially. Due to the lack of data, it cannot be determined if the risk of miscarriage is increased in women with von Willebrand disease (vWD).
The aim of our study was to clarify the association between inherited bleeding disorders and pregnancy loss.

Patients and Methods:

Subjects
Concerning this investigation we included 91 female patients with two [n=46] or more [n=45] miscarriages occurring prior to 28 weeks of gestation and/or stillbirth without apparent reason. The median age of the examined group at the time of first fetal loss was 29 years, ranging from 17 to 41 years.

Methods
At first we compiled a detailed clinical history of bleedings of all patients. Subsequently, we performed various tests to gather information regarding coagulation abnormalities and thrombophilic defects. Therefore a molecular and functional assessment of the following data was performed:
Coagulation factors, vWF:Ag, vWF:RCo, phospholipid antibodies, hyperhomocysteinaemia (HHCY), protein S (PS), protein C (PC), antithrombin (AT) and FV-Leiden mutation (G1691A), FII mutation (G20210A) and MTHFR C677T.

Results:
In our investigated population consisting of 91 women we registered 299 pregnancies of which 240 resulted in fetal loss, 232 prior to week 28 of pregnancy and 8 stillbirths.
Seven out of 91 patients (8%) were carriers of inherited coagulation disorders; vWD: n=2 (2%), FVII deficiency: n=3 (3%), thrombocytopathy: n=2 (2%). In our study collective there was no increased rate of patients with vWD. None of the patients showed a FXIII- or fibrinogen deficiency. However, 17 patients (19%) have a bleeding diathesis.
In 55 patients (60%) we could detect the following thrombophilic defects:
FV-Leiden (G1691A): n=10, MTHFR C677T: n=42, PS: n=1, PC: n=1, APS: n=1.

Conclusion:
The incidence of vWD patients in our miscarriage collective is the same as the overall incidence of vWD patients in the general population. Therefore vWD is not associated with an increased risk of fetal loss.

Disclosures:
No relevant conflicts of interest to declare.
Outcome of Splenectomy On Adult Idiopathic Thrombocytopenic Purpura (ITP)
Authors: Dutta Tarun K. , Vy Vishnu , Basu Debdatta 
Published: October 2019

Abstract
Abstract 4690

Aim:
To study outcome of splenectomy on adult ITP patients (both in prospective and retrospective groups)

Patient and Methods:
Two groups of ITP patients were studied. They were as follows:
(i) Retrospective group – Twenty two patients who underwent splenectomy during last twenty one years
(ii) Prospective group – All patients admitted during last three years with a minimum follow-up of six months (29 patients)

Result:
Retrospective group: Twenty two patients had undergone splenectomy during last twenty one years. Median time from diagnosis to splenectomy was 32 months. Median platelet count was 28,000/μl with some form of drug treatment (before undergoing splenectomy). Median post-splenectomy follow-up was 54 months (maximum 252 months). Eleven (50%) patients had either primary failure or relapse following splenectomy during subsequent years. The cumulative break-up figure was as follows:
Primary failure – 3 (13.6%)
At 24 months – 7 (31.8%)
At 5 years – 9 (40.9%)
At 10 years – 11(50%)
Prospective group: Out of 29 patients of ITP enrolled according to inclusion criteria of minimum six months’ follow-up, 20 had complete remission with steroids; nine had primary failure. Out of 20 patients with complete remission, two had relapse within six months of remission. Out of total 11 patients with failure to response to steroids (nine primary failure and two secondary failure), six patients agreed to undergo splenectomy. Three patients had complete remission till last follow-up (maximum follow-up was for 23 months). Two had primary failure following splenectomy and one had relapse. Five patients who did not agree for splenectomy are in complete or partial remission with azathioprine.

Conclusion:
At the end of two years in retrospective group, almost one-third of 22 patients who underwent splenectomy had either primary failure or relapse. Similarly in prospective group, though small in number, at the end of 23 months itself, three of six patients who underwent splenectomy had either no response or had relapsed. Thus this study questions the utility of splenectomy as second-line treatment after steroid failure. Rather, patient may be given a choice to opt for other form of drug treatment after steroid failure and advised splenectomy as and when unavoidable. Nevertheless, any patient opting for splenectomy should be cautioned that there is a fair chance of relapse later in life. Furthermore, it appears incidence of relapse following splenectomy is higher in Indian patients as compared to that in the Western patients.

Disclosures:
No relevant conflicts of interest to declare.
Rapid Anuric Acute Kidney Injury After the Administration of IV Anti-D in a Teenager
Authors: Haggett L. Kristy , Ayyanar Kanyalakshmi , Shoemaker Larry 
Published: October 2019

Abstract
Abstract 4691

Introduction:
A 16 year old male developed dark brown urine and prolonged anuric renal failure requiring hemodialysis after receiving IV anti-D. He was diagnosed with idiopathic thrombocytopenia purpura (ITP) after presenting with diffuse petechiae and a platelet count of 7000/μl, about a week after onset of viral prodrome that had resolved 2 days before. The white cell count, hemoglobin, PT, PTT, INR, and direct Coomb’s screen (IgG and complement) values were normal/negative at initial presentation, as were plasma chemistries, including LDH and uric acid levels. Except for small ketones and small heme reactions, the initial urinalysis was also unremarkable. Following IV anti-D, the patient developed intravascular coagulation concurrent with hemolysis and renal failure.

Method:
In this case report we describe a teenager who presented with ITP and rapidly developed severe anuric acute kidney injury (AKI) associated with mild intravascular hemolysis and coagulopathy. We review previous reports of IV Anti-D associated AKI, in order to identify common risk factors that may be used as a pre-treatment screen.

Result:
Anuric renal failure following IV anti-D has previously been reported and is a profoundly rare complication associated with a high risk of death. There is no reliable screening test, as this case illustrates. The clinical and laboratory course in this teenager, as well as from other reported cases, lead us to speculate that while hemolysis following IV-anti D infusion is necessary for the development of acute renal failure, it is insufficient unless there is a concurrent or antecedent intravascular coagulopathy. We suggest that the D-dimers assay should be formally evaluated as a screen prior to IV anti-D therapy to identify those individuals at risk for this life-threatening adverse reaction.

Conclusion:
IV anti-D is a good option for the treatment of ITP but the risks should be seriously considered prior to administration. A preliminary workup should be initiated prior to therapy. Other forms of treatment may be necessary in patients with evidence of renal insufficiency, hemolysis, recent EBV infection, known positive C-antigen or evidence of coagulopathy. We are planning a prospective study to evaluate the usefulness of obtaining a D-dimer in ITP patients prior to treatment. This will elicit information that is currently unavailable regarding the frequency of positive D-Dimers in patients with ITP prior to treatment.

Disclosures:
No relevant conflicts of interest to declare.
IFN-γ Level Could Be an Important Indicator to Determine Optimal Timing for Treatment or Prevention of GVHD in NSG Xenogeneic Model
Authors: Lee Young-Ho , Jang Yun Kyung , Kim Miyeon , Choi Soo Jin , Jang Seongsoo 
Published: October 2019

Abstract
Abstract 4704

Background:
We established xenograft model for graft-versus-host disease (GVHD) using human peripheral blood mononuclear cells (PBMC) in NSG mice. In addition, we also investigated the optimal timing for treatment or prevention of GVHD by observing the changes of inflammatory cytokines in xeno GVHD-induced mice.

Materials and Methods:
We infused various numbers of hPBMCs intravenously into irradiated NOD.scid gamma (NOD.Cg-PrkdcscidIL2rgtm1Wjl/SzJ, NSG) mice and assessed the optimal dose of hPBMCs for GVHD model by measuring GVHD clinical score and histopathologic findings as well as inflammatory cytokines.

Results:
We observed the compatible findings with GVHD by clinical score as well as immunohistochemical analysis which showed abundant invasion of lymphocytes in the lung, liver, kidney, and small intestines in xeno GVHD-induced mice. On administration of 1 × 106 and 2.5 × 106 hPBMCs, all NSG mice died on 41.6±6.8 days and 24.0±10.4 days, respectively. In contrast, 5 out of 6 NSG mice transplanted with 0.5×106 of hPBMCs survived until 89.6±23.2 days. Additionally, the changes of inflammatory cytokines were analyzed in NSG mice using 1×106 of hPBMC. The concentrations of IFN-γ were markedly increased from day 18 to day 36, however, TNF-α, and IL-2 were rarely detected during 36 days. CD8+ T cells were detected 2–3% in only 1 out of 3 mice and CD 56 was not appeared at all.

Conclusion:
These results demonstrated that 2.5×106 of hPBMC was optimal for acute GVHD and 0.5×106 of hPBMCs for chronic GVHD model in NSG mice. In addition, the changes of IFN-γ levels would provide an important evidence for the optimal timing for treatment or prevention of GVHD.

Disclosures:
No relevant conflicts of interest to declare.
Patients with Monosomal Karyotype in Acute Myeloid Leukemia Is Prognostically Worse Than with Complex Karyotype
Authors: Xiaoli Liu , Na Xu , Qingfeng DU , Dan Xu , Fanyi Meng , Lulu Xu , Jinfang Zhang , Bintao Huang , Xujing Luo 
Published: October 2019

Abstract
Abstract 4735
Purpose: Monosomal karyotype (MK) refers to the presence of two or more distinct autosomal monosomies or a single monosomy associated with a structural abnormality. To analyze the prognosis of cytogenetic components of a complex karyotype or Monosomal Karyotype in acute myeloid leukemia (AML) except acute promyelocytic leukemia(APL). Patients and Methods:Cytogenetics and overall survival (OS), Disease free survival(DFS) were analyzed in 551 AML patients age 14 to 60 years in our center.Results: There ware 235 patiets with cytogenetic abnormalities, 25 cases with inv(16)(p13.1q22) or t(16;16)(p13.1;q22),and 63 cases with t(8;21); 31 cases (13.2%)met the criteria for MK and 39 cases (16.6%) had a complex karyotype without monosomies. OS was significantly inferior in patients with MK compared with those with a complex karyotype without monosomies (P<0.01;HR 1.85,95% confidence interval(95%CI),0.95-2.81). There was no difference between MK cases with complex karyotype cases in DFS (P>0.05□GHR 3.42,95% confidence interval(95%CI),2.96-6.70). There was significant difference in regardless of whether OS or DFS between MK+ patients with MK− patients (P<0.01). Conclusion: MK was one of independent risk factor in AML patients.

Disclosures:
No relevant conflicts of interest to declare.
Utility of Blood Cultures in Febrile Patients in a BCSH Level 4 Centre
Authors: Lee Sophie , Kandiah Kesavan , Holyhead Kate , Aung Sandar , Smith Neil , Nikolousis Emmanouil , Paneesha Shankaranarayana 
Published: October 2019

Abstract
Abstract 4779

Objective:
To describe the epidemiology of bacterial organisms in a level 4 haematology centre and to investigate the prevalence of positive blood cultures at various time points in a febrile patient

Methodology:
A retrospective review was performed on 138 haematology patients who had blood cultures taken on ward 19 for febrile episodes at Heartlands Hospital, a BCSH Level 4 centre over a 6 month period from 1/5/2009 until 30/11/2009.

Results:
There were 704 blood cultures performed on 138 patients for 246 ‘febrile’ episodes. There were 59 positive blood cultures.
Patients with AML and DLBCL are most likely to require blood cultures as a result of febrile neutropenia.
Coagulase Negative Staphylococcus is the most common organism isolated from blood cultures in neutropenic patients during ‘febrile’ episodes.
There was only one pathogen cultured that was resistant to the first line antibiotic (Pipercillin/Tazobactam) that was used at this Trust.
The incidence of positive blood cultures at onset of fever is 15% is comparable to that seen in other institutions of similar patient populations. This decreased to 1.5 % at 24 hours, 1.7% at 48 hours and 6.3% at 72 hours.

Conclusion:
Based on the results above, it appears reasonable in stable patients to reduce the number of blood cultures done to 72 hours after the initial culture.
At the time of this review, the antibiotic policy in place at HOE NHS trust is appropriate for the pathogens that normally affect this patient population.
There should be regular audits to observe the epidemiology of microbials that affect haematology patients in this region and also to monitor their antimicrobial resistance to ensure appropriate first line antibiotics are in use.

Disclosures:
No relevant conflicts of interest to declare.
Application of Mass Cytometry to Measure Proliferation During Normal and Malignant Hematopoietic Differentiation
Authors: Behbehani Gregory K. , Bendall Sean C , Clutter Matthew , Medeiros Bruno C. , Fantl Wendy J. , Nolan Garry P. 
Published: October 2019

Abstract
Abstract 4782
Mass cytometry is a recently introduced proteomic technology that permits simultaneous measurements currently of as many as 40 parameters per single cell, including surface markers and intracellular signaling molecules and has recently provided a system-wide view of immune/hematopoietic cell differentiation within human bone marrow (Bendall et al, Science 2011). Given the unprecedented level of detail at the single cell level this approach provides, this technology is ideal for delineating the molecular and cellular basis of tumor heterogeneity. As an extension from our recent mass cytometry studies, we have now developed a method to perform cell cycle analysis by utilizing uridine incorporation, simultaneously with determinations of other cell cycle phase markers such as cyclins A, B1, and D as well as phosphorylation of retinoblastoma protein, histone H3, plus markers of apoptosis and other critical markers that demarcate malignant dysregulation. This allows for cell cycle state characterization that can be employed in both cell lines and primary cells growing in vitro or in vivo. We have combined this new method with a hierarchical clustering algorithm (SPADE) to profile the cell cycle state distribution across the continuum of hematopoietic differentiation in normal bone marrow. We observe the expected quiescence of terminally differentiated cells, hematopoietic progenitor and stem cell populations, and note that the majority of cell proliferation is confined to immunophenotypically immature cell populations of the myeloid, erythroid and monocytic linages. We have begun a broad comparison of these “normal” proliferation states to those observed across punctuated states of malignant progression that vary in “differentiation” of malignant cells in primary human sample in patients with acute myeloid leukemia revealing. The distribution of proliferation across these subpopulations generally parallels that of normal samples with more immunophenotypically “differentiated” AML cell populations having lower proliferative rates, however, not all AML patient samples follow this trend.

Disclosures:
Fantl: Nodality, Inc.: Equity Ownership.