bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Characteristics and Laboratory Analysis of Patients with Thrombocytopenia and Thrombocytosis.
Authors: Do Young-Rok , Kim Jin Young , Park Woo Young , Lee Sang Min , Kwon Ki Young 
Published: April 2020

Abstract
The normal range of platelet counts of peripheral blood is 150–450 × 109/L. Decreased platelet count results in the increased risk of bleeding. On the other hand, thrombosis formation is more prevalent in the patient of thrombocytosis. The mean platelet volume(MPV) is the mode of the measured platelet volume. There is an inverse relationship between platelet size and number. Therefore, the total platelet mass, the product of the MPV and platelet count is closely regulated. When platelets decrease in number, bone marrow megakaryocytes are stimulated by thrombopoietin, and their nucleus becomes hyperlobulated, with much greater ploidy. These stimulated megakaryocytes produce larger platelets. The platelet distribution width(PDW), is an indicator of the degree of variation in platelet size. PDW is defined as the coefficient of variation of the distribution of individual platelet volumes. So PDW is rising if the platelet destruction is increased while MPV is decreased. 48,340 patients were performed CBC test at Dong-san medical center through out the year of 2004. The platelet count below 150 × 109/L were 5,501(11.4%). Below 100 × 109/L of Platelet count is 2,303(41.8%). Platelet count Below than 20 × 109/L is 73(1.3%), 20–50 × 109/L is 323(5.9%), 50–100 × 109/L is 1,907(34.6%). Hemoglobin is 11g/dL in 50–100 × 109/L group and the hemoglobin is also rose in proportion to platelet count. WBC count is 10,540/L in below 20 × 109/L group and WBC count is decreased in proportion to platelet count. MPV is 9.5fL in 20–50 × 109/L group. PDW is 48.54% in below 20 × 109/L and the percentage is rose in proportion to platelet. Total bilirubin is 3.08g/dL in 20–50 × 109/L. Cause of thrombocytopenia is chronic liver disease, malignancy, infection and hematologic disease and secondary origin is more frequent than primary origin. Patients with thrombocytosis are 8,027(16.6%). The platelet count more than 600 × 109/L is 1,199(14.9%), 600–1,000 × 109/L is 1,051(13.1%), above 1,000 × 109/L is 148(1.8%). The PDW is 49.2% in 600–1,000 × 109/L group, 53% in above 1,000 × 109/L group.
New Compound Heterozygous Mutations of GPIIb in Patient with Glanzmann Thrombasthenia.
Authors: Yu Ziqiang , Su Jian , Bai Xia , Wang Zhaoyue , Ruan Changgeng 
Published: April 2020

Abstract
Glanzmann thrombasthenia (GT) is a homozygous or compound heterozygous autosomal recessive bleeding disorder caused by the qualitative or quantitative deficiency of integrin GPIIb-IIIa, which acts as the receptor of platelet fibrinogen. Here we report a case of GT with a compound heterozygous mutation in GPIIb according to the results of flow cytometry and genetic investigation.The flow cytometry was used to measure the average amounts of integrin GPIIb-IIIa on the patient’s platelets, and all 30 exons of GPIIb were amplified and sequenced with the corresponding primers.The average fluorescence intensity of integrin GPIIb-IIIa were 3.07 and 12.5, respectively, compared with 23.7 and 254, respectively, in the normal healthy individuals. And sequencing analysis of all exons of GPIIb demonstrated that there existed following compound heterozygous mutations in GPIIb gene: one heterozygote mutation (68 C→A) in the 1st exon, which resulted in Pro 23 His substitution in signal peptide domain; one nonsense heterozygous mutation (1750 C→T) in the 17th exon, which result in premature termination; one heterozygote mutation (2159 T→C) in the 21stexon, which resulted in Leu 720 Pro substitution. According to Glanzmann thrombasthenia database of ISTH (http://sinaicentral.mssm.edu/intranet/research/glanzmann/listmutations?mut=GPIIb), 68 C→A mutation and 2159 T→C mutation are novel mutations in the GPIIb heavy chain. These compound heterozygous mutations in GPIIb gene might be a novel pathogenetic mechanism of GT, which impaired the protein translation and co-expression with GPIIIa on the membrane of platelet.
Hemorrhagic Fever in Schoenlein Henoch Purpura.
Authors: Corinaldesi Giorgio , Corinaldesi Christian 
Published: April 2020

Abstract
Schoenlein Henoch Purpura (SHP) may show a cohort of symptoms such as: a palpable purpuric rash where lesions may be prominent mostly on lower extremities, abdominal pain, arthritis and nephritis. It is an inflammatory disorder characterized by an IgA-mediated vasculitis with immune complexes deposition in smaller veins, capillaries and arterioles which often occur as a response to infections (mycoplasma, streptococcus group A, Campylobacter enteritis, Helycobacter, Herpes virus, Parvovirus B19, Epstein-Barr virus), or to an exposure to allergens, drugs, some particular food, cold, or even insect bites. Symptoms are often dramatic at the onset, and the exitus occurs sadly between 30 – 50% of the patients, despite the therapeutic support, for this reason the diagnosis and the therapy should be precocious. Clinically we can observe multi organ failure, hypotension, flushing, capillary leak haemorrhage secondary to thrombocytopenia, platelet dysfunction, disseminated intravascular coagulation, shock. We have studied a young boy (19 years old) with an urticarial wheals, erythematous maculo-papules, purple spots, and larger petechiae, migrant arthritis and arthralgia, renal disease (low grade hematuria with proteinuria), weakness, necrotic and hemorrhagic plaques, with haematemesis, diarrhoea, abdominal pain, fever (38.5°/39.5° C), and increased blood level of human Parvovirus-B19 NS1-gene component. We performed a skin biopsy of SHP that showed: leukocytoclastic vasculitis, with angiocentric neutrophilic infiltrate, fibrin deposition and focal fibrinoid necrosis. We also evaluated a kidney biopsy which showed: mild increase of mesangial cellularity, with segmental capillary luminal leukocytes and scattered capillary wall fuchsinophilic deposit, while the diagnostic finding is constituted by granular mesangial IgA with C3. The management is based on support therapy, with plenty of haemotrasfusions, and immunosuppressive therapy (prednisone 40 mg os/die, and cyclophosphamide100–200 mg/daily/os for 30–60 days (may decrease inflammation, capillary permeability and suppressing granulocytes activity and migration. The prognosis is usually excellent when the syndrome is self-limited and resolves spontaneously often 4/8 weeks without recurrence. Sometimes the diagnostic investigation may show an elevated level of vascular IgA deposition (direct immunofluorescence), elevated plasma levels of C3 and C4, elevated levels of IgA, ANCA (antineutrophil cytoplasmic antibodies: pANCA anti-MPO, cANCA anti-PR3), CRP, fibrinogen, ICAM-1, and increase of TNF, IL-1, IL-6, TGF-beta that reflect endothelial cell damage and dysfunction.
A High Purity Factor VIII/vWF Complex Concentrate Is Effective in the Management of Mild Hemophillia A with Inhibitors: A Case Report.
Authors: Dukka Srivasavi , Kaye Susan , Ashcroft John , Hill Anita , Parapia Liakat A. 
Published: April 2020

Abstract
Introduction: Inhibitor development in Mild Haemophilia A (MHA) is an uncommon complication, occurring in approximately 15% of MHA patients. Risk factors associated with the development of inhibitors in MHA include change in recombinant factor VIII (rFVIII), intensive replacement therapy, immunological challenges and missense mutations in the FVIII gene, including Tyr2105Cys mutation on exon 22. Only few reports have addressed the therapeutic options to eradicate these inhibitors, either by immune tolerance or immunosuppressive protocols.
Patient: We present a case report of a 36-year-old MHA patient (original factor VIII activity of 17.5% (10–20%) with a Tyr2105Cys mutation. He developed a low titre inhibitor after intensive exposure to rFVIII to cover for spinal epidural steroid injection, switch of recombinant product (full length rFVIII to B-domain deleted rFVIII) and intensive antiviral treatment (pegylated interferon and ribavarin) for Hepatitis C. His quality of life was very poor due to recurrent spontaneous bleeds - ecchymoses, haematomas and haemarthroses. His baseline factor VIII activity dropped to 1% with an initial inhibitor titre of 2.6 BU and factor VIII recovery of less than 25%.
Results: The patient responded positively when started on an immune tolerance protocol with a low dose of high purity FVIII/vWF complex concentrate. All clinical parameters improved two weeks after commencing 50 IU/kg on alternate days of the high purity FVIII/vWF product. FVIII recovery levels improved to 50% and he was asymptomatic in terms of bleeding manifestations for the following 17 weeks. Inhibitor titres stabilised at 3.5 BU. Recently, the recovery levels dropped to 26% and the frequency of bleeds increased, necessitating treatment with additional doses. The immune tolerance dose of the high purity FVIII/vWF was increased to 100IU/kg/day. Haemostatic and clinical parameters again recovered (factor VIII recovery levels of 43%) with no further spontaneous bleeds.
Conclusions: The use of recombinant factor VIII, especially high intensity replacement may pose a risk of inhibitor development and bleeding complications during the management of MHA patients with Tyr2105Cys mutation. An immune tolerance protocol with FVIII/vWF concentrate is effective in the management of MHA patients with inhibitors and can improve the quality of life soon after the start of the treatment. There is no anamnestic response observed. Though low dose immune-tolerance protocol may be effective, the benefits may be short-lasting, necessitating treatment with high daily dose protocol.
Identification of Trigger Factors Initiating an Acute TTP Episode in 68 Patients.
Authors: von Auer Charis , Wilken Andreas , Scharrer Inge 
Published: April 2020

Abstract
Recent research efforts have provided significant insight into the pathogenesis of thrombotic thrombocytopenic purpura (TTP). However, the low incidence of the disease hampers the identification of trigger factors initiating an acute TTP episode. In the present work data from 68 TTP patients were analyzed. The patients were asked by a questionnaire to provide data concerning age, gender, medical history, underlying and concomitant diseases and potential triggers. Additional laboratory and clinical data from onset of disease and remission phase were obtained by a second questionnaire completed by the physicians. Our study showed that long term abuse of nicotine is a predisposing factor with an OR of 3.19. The OR for obesity and development of TTP was 2.01. The influence of nicotine abuse has not yet been described whereas the association between obesity and development of TTP is already known. The intake of oral contraceptives (13 of 46 women/28%) of Tamoxifen, of Fluvastatin, of Ticlopidine and of Quinine was identified to be potential triggers. 55% (34 patients) of the patients reported infections and inflammations as triggers (mostly influenza (n=16) and gastroenteritis (n=14)). The relation of female and male patients was 3:1. The mean age, in which the initial TTP episode occurred, was significantly lower in female patients compared with the male patients (33.8 versus 43.8 years). Severe ADAMTS-13 deficiency was found in 91% in all investigated episodes of the patients. Inhibitory activity was associated with severe ADAMTS-13 deficiency in 81% of the cases. The comparison of patients during remission with and without relapses of TTP revealed a significant lower ADAMTS-13 activity in patients with relapsing TTP compared to patients without a relapse of TTP. This result suggests that ADAMTS-13 activity has prognostic value with respect to the occurrence of relapse.
Multiple Complete Responses in a Phase 1 Dose-Escalation Study of the Antibody-Drug Conjugate SGN-35 in Patients with Relapsed or Refractory CD30-Positive Lymphomas.
Authors: Younes Anas , Forero-Torres Andres , Bartlett Nancy L. , Leonard John P. , Lynch Carmel , Kennedy Dana A. , Sievers Eric 
Published: April 2020

Abstract
Figure Figure
Background: The antibody-drug conjugate SGN-35 is being developed as a targeted therapy for Hodgkin lymphoma (HL) and other CD30-expressing hematologic malignancies. SGN-35 binds to CD30 and is internalized into the tumor cell, with subsequent release of the antitubulin agent monomethyl auristatin E (MMAE). Binding of released MMAE to tubulin disrupts the microtubule network, prompting cell cycle arrest and apoptosis.
Methods: A multicenter phase 1 dose-escalation study was conducted in 45 patients with refractory or recurrent CD30-positive hematologic malignancies, including HL (n=42), systemic anaplastic large cell lymphoma (sALCL; n=2), and angioimmunoblastic T cell lymphoma (n=1). Median age was 36 (range 20–87) and most patients (93%) had an ECOG performance status of 0/1. Patients had a median of 3 prior chemotherapy regimens (range 1–7); 73% of patients previously received an autologous stem cell transplant. SGN- 35 dose levels ranged from 0.1 to 3.6 mg/kg (2-hr outpatient IV infusion, premedications not required) every 3 weeks. Patients with stable disease or better after 2 doses were eligible to receive additional doses of SGN-35. The study has completed enrollment and a weekly SGN-35 dosing regimen is currently being investigated.
Results: The most common adverse events (occurring in ≥20% of patients) were fatigue, pyrexia, nausea, and diarrhea. Dose-related neutropenia was observed. The maximum tolerated dose was 1.8 mg/kg every 3 weeks. One patient treated at 3.6 mg/kg developed febrile neutropenia and presumed sepsis and died 14 days after the 1st dose of SGN-35. Exposure to SGN-35 increased relative to dose level, and the terminal elimination half-life was 5.0 ± 1.8 days at 1.8 mg/kg. Approximately 75% of patients reporting B symptoms at baseline experienced symptom resolution on study. Most patients (86%) had reductions in target lesion size. Among 28 evaluable patients treated at doses ≥1.2 mg/kg, the objective response rate (CR+PR) was 46% (n=13) and the complete remission rate was 25% (n=7). Two additional PRs were observed in the 0.6 mg/kg cohort. Median response duration to date is 22 weeks (range, 0.1+ to 38+ weeks). Thirteen patients continue on study.
Conclusions: The antibody-drug conjugate SGN-35 induced durable objective responses in heavily pretreated Hodgkin lymphoma and systemic ALCL patients at well-tolerated doses, providing evidence of selective tumor targeting. Pivotal studies with SGN-35 are planned.
Enhanced Fibrinolysis of Coarse Fibrin Networks Reflects Cleavage of a B Knob Containing Fragment(s)
Authors: Galanakis Dennis K. , Neerman-Arbez Marguerite , Henschen Agnes , Kudryk Bodan 
Published: April 2020

Abstract
Coarse fibrin network clots display faster fibrinolysis than their fine network counterparts (Collet et al, Arterioscler Thromb Vasc Biol2000, 20: 1354–61), and this is ostensibly of pathophysiologic relevance. Since relative to fine networks, coarse networks can be predicted to possess a relatively higher content of “B knob” (-”b” and/or -”a hole”) contacts, we investigated whether or not such contacts are more susceptible to plasmin than their A knob counterparts. Owing to much slower FpA than FpB release from Aα G16H fibrinogen, its clots acquire a high content of B knob contacts throughout polymerization (Galanakis et al, Bld Coag Fibrinol, 2007, 18: 731–737) and were therefore used for this purpose. Plasminogen-free fibrinogen was obtained by Lys-Sepharose chromatography, and clots of isolates from one homophenotypic (HM) and one (unrelated) heterophenotypic (HT) Aα G16H proband were compared with normal controls. Plasmin digests of fibrinogen, monitored by PAGE-SDS, disclosed no differences from controls. Thrombin was added to fibrinogen (1–5 μM), pH 7.4, 8 mM CaCl2, with or without 20% afibrinogenemic plasma so as to achieve &gt; 96% clottability. For lysis times, clots were suspended in 2 volumes of a lysis solution. For turbidity (340 nm) measurements the lysis solution was carefully layered on the cuvette clot top. To obtain clots of similar turbidities 0.8 to 1.2 thrombin U/ml were used. The lysis solution contained either 2 μM plasmin in buffer (37º) or 80 μM rtPA with or without 50 μM plasminogen. Selected clots were prepared in solutions containing either anti-β 15–42 IgG (Mab, 3 mols/mol fibrin) or the GlyHisProArgProOH peptide (50 mols/mol fibrin). Using fibrin (70 nM)-enhanced glu-plasminogen (250 nM) activation by rtPA (10 μM) and S2251 substrate (40 mM), no differences (405 nm) among control, HM, and HT fibrin could be shown in two separate sets of experiments. Clot lysis times (n=3) were 31% (HM) and 54% (HT) of controls, respectively. Turbidity measurements (n=3) also disclosed HM and HT clot lysis onset ~2 and 1.5 fold faster than controls, but similar lysis rates. Duplicate clots lacking &gt;90% of intact αC (i.e. fraction I-9) yielded similar differences. Also assessed by turbidity, clots formed in Mab containing buffer lacked lysis differences from non-immune IgG controls. Using turbidity measurements of normal fibrin, lysis differences between coarse and fine clots were abolished when clots had been obtained from fibrinogen/GlyHisProArgProOH solutions (n=2). We conclude that B knob contacts are constitutively more susceptible to plasmin than their A knob counterparts. This property is attributable to faster release by plasmin of at least one of the two β 15–53 (B knob containing) fragments relative to release of either or both α 17–19 (A Knob) fragments from the DDE complex (Olexa et al, Biochemistry1981, 20:6139–45).
Invariant NKT Cells Regulate Osteoclast Development and Function Under Homeostatic and during Conditions of Immune Activation
Authors: Hu Ming , Basssett J.H. Duncan , Danks Lynette , Spanoudakis Emmanouil , Xu Ke , Howell Peter GT , Boyde Alan , Horwood Nikki , Williams Graham , Roberts Irene AG , Karadimitris Anastasios 
Published: April 2020

Abstract
Invariant NKT cells, a small subset of immunoregulatory T cells restricted by the glycolipid-presenting non-polymorphic CD1d molecule, are able to modulate a variety of innate and adaptive immune responses. Osteoclasts (OC) are bone resorbing polykaryons of hematopoietic lineage, that have the capacity to regulate myeloid cell egress from bone marrow (BM) thus making them an integral part of the innate immune response. We and others previously showed that NKT cells regulate hematopoiesis in mice as well as humans. In this work, we investigate the role of NKT cells in OC development and function in homeostasis and after their specific activation by the model glycolipid alpha-galactosylceramide (aGC). Using quantitative back scattered electron scanning microscopy, we found that TCR Ja18 −/− mice which selectively lack development of NKT cells, exhibit a moderate osteopetrotic phenotype affecting trabecular as well as cortical bone. Histologically, these mice had the same number of TRAP+ OC as WT mice suggesting a maturation rather developmental defect in the TCR Ja18 −/−-derived OC. In vitro differentiation in the presence of RANKL and M-CSF showed that while TCR Ja18 −/− BM cells are capable of forming multinucleated OC, these, as assessed by confocal microscopy, fail to form F-actin rings and sealing zone and thus are unable to resorb bone. Further underscoring the effect of NKT cells in this process, CD45.1+ BM cells highly purified from CD45.2+ WT/CD45.1+ TCRJa18 −/− mixed BM chimeras displayed restoration of their OC F-actin rings. Next we investigated whether in vivo activated NKT cells regulate OC function. We found that a single injection of aGC dramatically increased the number of CD3-B220-CD11b-c-fmshighc- kithigh BM OC progenitors and accelerated the in vitro development of OC in WT but not TCR Ja18 −/− mice. Furthermore, this resulted in high serum levels of IFN-g and IL-4 but not IL-1 or IL-17. An aGC-mediated increase of OC progenitors was observed in IFN-g −/− but not IL-4 −/−mice suggesting that NKT cell-derived IL-4 is the main cytokine promoting osteoclastogenesis in this context. Taken together, our data demonstrate a novel role of NKT cells in homeostatic bone mass regulation and in the orchestration of innate immune responses through regulation of OC development and function.
A Potential Novel Therapeutic Approach for Fanconi Anemia
Authors: Lambert W. Clark , Brown Monique M 
Published: April 2020

Abstract
Lymphoblastoid cells from normal subjects and from patients with the bone marrow failure and cancer prone inherited disease, Fanconi anemia (FA) were treated in culture with psoralen plus ultraviolet A radiation (PUVA) in a scheme shown to produce interstrand crosslinks in cellular DNA. Hypersensitivity to DNA interstrand crosslinks, with associated increased clastogenicity, is considered to be a diagnostic hallmark of the disease. Following this cells were treated with hydroxyurea, 5 fluorouracil, or high dose thymidine for 24 hours. Clastogenicity and cytotoxicity, measured as trypan blue exclusion, were then found to be markedly increased in FA cells but not in FA cells subsequently treated with any of these other agents. Similar results were also found when all drugs were removed after these treatments and the cells cultured for 10 days without any drug in colony forming ability assays. We propose that the mechanism is related to decrease in the rate of DNA synthesis, which we have shown occurs in normal but not FA cells following PUVA, and which is also produced by these other drugs in the concentrations used here. Hydroxyurea has been used for many years as a safe and effective treatment for sickle cell anemia. It is now proposed as a possible treatment for Fanconi anemia to delay or even prevent development of bone marrow failure and/or other complications, including leukemogenesis and carcinogenesis, with or without prior bone marrow transplantation.