bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection and Clinical Significance of Thrombomodulin in Both Plasma and Tissue Extracts of Cancer Patients.
Authors: Xu Xiaohua , Huang Liansheng , Lu Xingguo , Zhang Xiaohong , Zhao Xiaoying 
Published: October 2019

Abstract
Objective: To study the changes of thrombomodulin(TM) in both plasma and tissue extracts of cancer patients for evaluating its clinical significance.
Methods: Plasma TM levels were measured by enzyme-linked immunosorbent assay(ELISA) in both plasma of 188 cancer patients and 24 cancer tissue extracts including their adjacent non-cancer tissues.
Results: The plasma TM levels both in cancer patients and in metastasis patients were significantly higher than that in controls [(33.47±14.25)ug/L/(41.68±16.96)ug/L, vs (20.40±7.22)ug/L, P<0.01]. The plasma TM levels in cancer patients after operation decreased obviously than that before operation [(18.45±9.96)ug/L, vs (28.29±11.74)ug/L, P<0.01], whereas, the plasma TM levels in patients with recurrence and metastasis after operation increased obviously [(34.50±12.57)ug/L]. Among the type of cancer, the plasma TM levels in metastasis including lung cancers and gastric cancers and pancreatic cancers were significantly higher than that in non-metastasis respectively, but no significant differences were foundPOST http://www.call4abstracts.com/hem/body.pincluding gastric cancers and pancreatic cancers and nasopharyngeal cancers and large intestine cancers and laryngeal cancers (P>0.05). The TM levels in cancer tissue extracts were significantly lower than that in their adjacent non-cancer tissue extracts [(647.71±317.51)ug/L vs (1455.63±772.22)ug/L, P<0.01]. On the contrary, the plasma TM levels in these cancers were significantly higher than that in controls.
Conclusion: The rise of plasma TM levels in cancer patients was associated with metastasis and diffusion of cancers. The TM levels can be served as a sensitive index for judging progression and metastasis of cancers.
In-Vitro Stability of B-Domain Deleted Recombinant Factor VIII in Syringe-Based Continuous Infusion Devices.
Authors: Woloschuk Donna M.M. , Dyck Jennifer M. , Israels Sara J. , Toogood Peter 
Published: October 2019

Abstract
Continuous infusion (CI) factor VIII (FVIII) replacement is commonly used for serious bleeds in patients with FVIII deficiency. Clinicians lack stability information for Refacto®, a B-domain deleted recombinant FVIII (BDDrFVIII), when it is diluted or stored in CI devices for extended time periods. We studied BDDrFVIII to determine its concentration- and time-dependent stability and sterility when stored (reconstituted; reconstituted then diluted with normal saline) at ambient temperature in syringe-based CI devices (CADD-MicroTM; Baxter ColleagueTM). Three replicates of BDDrFVIII 125unit/mL and 25unit/mL admixtures were admixed aseptically then placed in CI devices that operated continuously for 48 hours. Samples (0.5ml) were obtained from control solutions (stored in the manufacturer’s glass vial) or expressed from the distal end of tubing at Hour −0.25 (priming volume), 0, 1, 2, 4, 8, 12, 24 and 48. Samples were stored at −70C until assayed for Factor VIII activity using a 1-stage automated assay and Refacto® [chromogenic equivalent] Standard. Results of FVIII assays for each trio of replicates were averaged. BDDrFVIII admixtures were considered stable if they retained ≥80% baseline (control) FVIII values. Recoveries for BDDrFVIII 125unit/mL admixtures remained stable and sterile for 48 hours when stored in the manufacturer’s glass vial, Baxter ColleagueTM or CADD MicroTM devices, sufficient for clinical use (Table). BDDrFVIII, when diluted to 25unit/mL, remained sterile but not stable when stored in Baxter ColleagueTM or CADD MicroTM devices, and is not recommended for CI in clinical settings. Loss of FVIII activity in BDDrFVIII 25unit/mL admixtures is thought to be due to binding of BDDrFVIII to device components.
%FVIII Activity of BDDrFVIII Stored in Infusion Devices
Hr 0 Hr 1 Hr 2 Hr 4 Hr 12 Hr 24 Hr 48 Mfr Glass Vial (Control) 92.5 93 90.7 90.8 93.2 76 80.7 CADD-Micro 125unit/ml 80 84 86.3 78.3 86.3 80 81.7 Baxter Colleague 125unit/ml 86.3 79 74 85 77.7 81 82.3 CADD-Micro 25unit/ml 65.7 61.3 56.3 59 57.5 59.7 56.3 Baxter Colleague 25unit/ml 18.7 19.3 33 24.3 27 27 27.3
TAFI and Diabetics.
Authors: Kubisz Peter 
Published: October 2019

Abstract
Background: A novel risk factor for thrombotic disorders is thrombin activatable fibrinolysis inhibitor (TAFI) which is also known as plasma procarboxypeptidase B. TAFI is a potent inhibitor of tissue plasminogen activator - induced fibrinolysis, impairing the process of clot lysis and causing a tendency to thrombosis development. The increased circulating plasma levels of TAFI were reported in type 2 diabetes mellitus (DM), obesity, insulin resistance and in hypercholesterolemic subjects. TAFI plasma level was significantly higher in diabetic patients with microalbuminuria than those in diabetic patients with normoalbuminuria and normal subjects. These authors suggest that increased plasma level of TAFI may be involved not only in hypofibrinolysis but also in the mechanism of vascular endothelial damage in patients with type 2 DM.
Aim of study: We evaluated the activity of activated TAFI (TAFIa) and its relation to another hemostatic and metabolic parameters in patients with diabetic nephropathy (DN).
Patients and methods: Eighteen patients (pts) with diabetic nephropathy (DN) − 14 pts type 2 DM / 4 pts type 1 DM, age 54,1±13,3 years (12 men, 6 women), fourteen pts with non-diabetic nephropathy (NDN), age 49,7±15,6 years (7 men, 7 women) and twenty healthy subjects were enrolled in the study. TAFIa (Actichrome Activity TAFI kit, American Diagnostica), soluble thrombomodulin TM (sTM), von Willebrand factor (vWF), tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), homocysteine (Hcy), D-dimers plasma levels and metabolic parameters including glycosylated hemoglobin (HbA1c) were measured.
Results: TAFIa plasma levels in DN pts were significantly decreased compared to NDN pts (7,22 ± 3,54 vs. 12,67 ± 6,99 ug/ml, p<0,01, respectively). After analysis the significant TAFIa decrease was only in those DN pts with hypercreatinemia and proteinuria. The sTM levels showed significant increase in DN pts with hypercreatinemia (p<0,0001). There was a significant positive correlation between TAFIa and HbA1c (r=0,50931, p<0,05).
Conclusion: TAFIa plasma levels didn′t differ significantly in patients with diabetic nephropathy compared to those in control healthy group. Decreased TAFIa plasma levels in our DN pts with proteinuria and hypercreatinemia compared to NDN group may be due to the secondary (compensatory) increased fibrinolysis as a consequence of hypercoagulability in pts with DM. TAFIa was in a close relation to the metabolic compensation of DM (HbA1c) that can be of clinical importance for DN pts.
The Murine Genome Contains Two Functional Kininogen Genes Leading to Tissue Specific Expression of High Molecular Weight Kininogen (HK) and Expression of a Novel HK Splice Variant.
Authors: Merkoulov Sergei , Komar Anton A. , McCrae Keith R. 
Published: October 2019

Abstract
High molecular weight kininogen (HK) plays an important role in the assembly and activation of the kallikrein/kinin system. While the human genome contains only a single copy of the kininogen gene, three copies are present in the rat (one K-kininogen and two T-kininogen). Here, we report that the mouse genome contains two homologous kininogen genes (overall homology 91%), denoted mHK1 and mHK2. Both genes are located on chromosome 16 in a head-to-head orientation, and contain open reading frames. The size of intronic sequences between the 11 kininogen gene exons is similar (Figure). HK mRNA transcripts derived from the mHK1 and mHK2 genes differ slightly in size due to gaps of 33 and 18 nucleotides in exon 10 of mHK2. RT-PCR analysis of HK gene expression in adult and embryonic murine tissues revealed that HK mRNA was derived from mHK1 in liver, adrenal and embryo, but from mHK2 in kidney and lung. HK mRNA derived from both genes was present in testis, brain and muscle, though expression levels were low relative to those in other tissues. HK mRNA was not detected in ovary, bone marrow, heart or bladder. mHK1-derived HK mRNA was alternatively spliced, as demonstrated by the presence of an HK mRNA transcript encoding a novel HK1 isoform, ΔmD5, that lacked the portion of exon 10 encoding Thr400 - Asp582 of HK domains 5 and 6. Examination of the putative promoter regions of the two genes using the MatInspector Professional program (Genomatix) demonstrated distinct differences, perhaps explaining in part their tissue-specific expression patterns. Like domain 5 of human HK (hD5), domain 5 of murine HK (mD5), in which the histidine and lysine-rich C-terminal region of this domain previously shown to mediate the antiangiogenic activity of domain 5 is highly conserved, inhibited endothelial cell proliferation. While the function of each of the kininogen genes in the intact animal has yet to be defined, characterization of the two genes may provide new information concerning the role of high molecular weight kininogen in development, normal physiology, and pathological processes.
Figure Figure
The Occurrence of Antibodies to Components of the Natural Coagulation Inhibitor System, Protein Z and Protheombin in Normal Pregnancy.
Authors: Ku De-Hui W. , Arkel Yale S. , Paidas Michael J. , Triche Elizabeth , Huang Shannon , Musto Jeffrey , Lockwood Charles J. 
Published: October 2019

Abstract
There are recent reports that indicate that antibodies to components of the natural coagulation inhibitor system and coagulation factors, such as FII, are associated with increased risk for thrombosis and adverse pregnancy outcomes (APO) in patients with autoimmune disease and the anticardiolipin syndrome. In view of the importance of the natural inhibitor system in regulating the prothrombotic process and particularly in the hypercoagulable milieu of pregnancy, we studied the occurrence of several of these antibodies in patients characterized with normal pregnancies (NP). We used 82 1st trimester (TRI), 64 2nd TRI, 78 3rd TRI, and 50 non-pregnant controls for this study. Our data are demonstrated in the tables below. The salient features; the PZ and PS IgM antibodies are greater than the non-pregnant controls throughout gestation but the PZ and PS IgG antibodies are greater than non-pregnant controls in the later phases of pregnancy. IgG and IgM antibodies to FII and PC are increased compared to non-pregnant controls throughout gestation. When the antibody levels are compared in NP in each trimester; PZ IgM increases in the 3rd trimester, PS IgG increase in each trimester and PS IgM in the first two trimesters. FII IgM increases in each trimester and IgG does not increase with gestation. PC IgM increases with each trimester and PC IgG remains unchanged. The prevalence of progressive increases in the antibody response is mainly IgM. This would tend to indicate more acute than chronic response and stimulation. These findings indicate that in NP an immune response is present in most pregnancies that can affect the hemostatic balance. Yet to be determined are the tipping points for pathological consequences.
Table 1
1st trimester (OD) 2nd trimester (OD) 3rd trimester (OD) CTR (OD) CTR=non-pregnant control Anti-PZ IgG 0.26+/−0.42 0.21 +/−0.31 0.30+/−0.29 0.19+/−0.14 Anti-PZ IgM 0.36+/−0.22 0.21+/−0.11 0.39+/−0.20 0.07+/−0.17 Anti-PS IgG 0.29+/−0.35 0.45+/−0.25 0.44+/−0.31 0.27+/−0.20 Anti-PS IgM 0.48+/−0.38 0.66+/−0.42 0.61+/−0.36 0.26+/−0.15 Anti-FII IgG 0.92+/−0.53 0.86+/−0.57 0.98+/−0.65 0.44+/−0.41 Anti-FII IgM 0.92+/−0.51 0.612+/−0.42 0.77+/−0.44 0.26+/−0.31 Anti-PC IgG 0.96+/−0.61 0.99+/−0.78 0.91+/−0.57 0.51+/−0.32 Anti-PC IgM 1.01+/−0.43 0.90+/−0.29 0.87+/−0.41 0.54+/−0.27
Table 2
1st vs 2nd 1st vs 3rd 2nd vs 3rd CTR vs 1st CTR vs 2nd CTR vs 3rd NS=non significant Anti-PZ IgG NS NS NS NS NS p<0.05 Anti-PZ IgM NS NS p<0.05 p<0.05 p<0.05 p<0.05 Anti-PS IgG P<0.05 P<0.05 NS NS p<0.05 p<0.05 Anti-PS IgM p<0.05 p<0.05 NS p<0.05 p<0.05 p<0.05 Anti-FII IgG NS NS NS p<0.05 p<0.05 p<0.05 Anti-FII IgM p<0.05 p<0.05 p<0.05 p<0.05 p<0.05 p<0.05 Anti-PC IgG NS NS NS p<0.05 p<0.05 p<0.05 Anti-PC IgM p<0.05 p<0.05 NS p<0.05 p<0.05 p<0.05
Acquired Hemophilia: Characteristics and Treatment Outcome of a Standardized Therapeutic Approach in a Singapore Series.
Authors: Ng Heng J. , Tan Daryl C.L. , Lee Lai H. 
Published: October 2019

Abstract
Introduction: Acquired hemophilia is a rare bleeding disorder with significant mortality risk but is yet highly treatable. Patients diagnosed with this condition in our institution have been treated with a standardized approach aimed at detecting and controlling bleeding early and inhibitor elimination.
Objective: Review the effectiveness and treatment outcome of our therapeutic approach to acquired hemophilia patients.
Methods: Consecutive patients diagnosed with acquired hemophilia over a period of 5 years from July 1998 till July 2004 were retrospectively reviewed for their underlying characteristics, responses to treatment, complications and subsequent outcome.
Results: 13 patients were recorded with age ranging from 17 to 89 years (median 66 years) and a male to female ratio of 10:3. Follow-up periods range from 5 to 56 months. All patients presented with variable degree of bleeding. Four patients were given recombinant factor VIIa (from 1 to 5 doses) for the control of life threatening bleeding. Three patients received prothrombin complexes as bypassing agents. One other patient received both agents..All patients received both cyclophosphamide (50–100mg/day) and prednisolone (1 mg/kg/day) for elimination of inhibitors at diagnosis. Six patients received intravenous immunoglobulin of 1 gm/kg/day for 2 days with this decision based on the severity of bleeding. Two early deaths were recorded from retroperitoneal bleeding and cerebral infarct following recombinant factor VIIa therapy, respectively. Another death occurred following sepsis with multiple co-morbidities, while being given immunosuppressive therapy. He was the only patient experiencing significant leucopenia while on cyclophosphamide therapy. Two patients were lost to follow-up subsequently. Of 8 patients evaluable for response to inhibitor eliminating therapy with cyclophosphamide and prednisolone, all but one achieved a complete remission within 7 to 71 days with a median of 41 days. Of these 7 patients, there was one early relapse, which occurred from non-compliance to treatment while it was being tailed down. Remission was successfully reinduced on reintroduction of both cyclophophamide and prednisolone. All other patients have remained in remission after discontinuation of therapy. The patient with failure of complete response had persistent low inhibitor levels without bleeding complications and died after 56 months of follow up from unrelated causes. Overall mortality of evaluable patients was 27% (3 out of 11).
Conclusion: Mortality remains significant in this condition with control of early bleeding risks and treatment complications paramount to survival. For the great majority of patients, our strategy affords effective inhibitor elimination and sustained remission of this condition
Monosomy 7 and Deletion 7q in Childhood AML. A Collaborative Study of 20 Study Groups.
Authors: Hasle Henrik , Alonzo Todd , Avrignon Anne , Behar Cathrine , Chang Myron , Creutzig Ursula , Fischer Alexandra , Forestier Erik , Fynn Alicira , Harbott Jochen , Harrison Christine J. , van den Heuvel-Eibrink Marry , Kaspers Gertjan , Locatelli Franco , Nöllke Peter , Polychronopoulou Sophia , Ravindranath Yaddanapudi , Razzouk Bassem , Reinhardt Dirk , Savva Natalia N. , Stark Batia , Suciu Stefan , Trebo Monika , Tsukimoto Ichiro , Webb David , Wojcik Dorota , Woods William G. , Zimmermann Martin , Niemeyer Charlotte M. , Raimondi Susana 
Published: October 2019

Abstract
Monosomy 7 (−7) and deletion 7q [del(7q)] are rare in childhood AML and are considered to be associated with a poor outcome. We retrospectively analyzed data on 267 children with de novo AML or RAEB-T (PB or BM blasts > 20%) with −7 or del(7q) with or without additional cytogenetic aberrations (other). Patients were diagnosed between 1985 and 2003. Karyotypes showed −7 (n=90), −7 other (n=82), del(7q) (n=22), and del(7q) other (n=73). All 24 patients with RAEB-T had −7 +/− other. The median age at diagnosis was 7.6 years (range; 0–18.1) with no difference in age distribution between cytogenetic subgroups. The most common additional cytogenetic aberrations were inv(3)/t(3;3) in 19 patients (−7, n=17; del(7q), n=2) and favorable aberrations [t(8;21), inv(16), and t(15;17)] observed in 25 patients (−7, n=3; del(7q), n=22). The 5-year overall probability of survival for the whole group was 39%, SE=3%, and survival was higher in patients with del(7q) +/− other compared with −7 +/− other (52% vs. 30%). The survival of patients with del(7q) and favorable cytogenetic aberrations (n=22) was higher than that of other patients with del(7q) (75% vs. 46%, p=0.026). There was no significant difference in survival for patients with −7 and −7 other. Complete remission (CR) was obtained in 188 patients (−7 +/− other 62%; del(7q) +/− other 88%), of these, 67 received hematopoietic stem cell transplantation (HSCT) in CR1. There was no significant difference (Mantel-Byar test) in survival for patients who received HSCT in CR1 (49%, SE= 7%) and those who received chemotherapy only (51%, SE=5%, 54% for patients surviving at least the median time to HSCT). In conclusion childhood AML subgroups −7 and del(7q) differ in their associated cytogenetic aberrations and response to therapy.
Comparison of Phenotypic Assessment and Mutation Detection in the Diagnosis of Carrier State in Hemophilia: Identification of 10 Novel Mutations.
Authors: Chuansumrit Ampaiwan , Sasanakul Werasak , Williams Ian , Goodeve Anne , Kadegasem Praguywan , Peake Ian 
Published: October 2019

Abstract
The carrier state in 54 females (A38, B16) at risk from 35 moderate and severe hemophilia families (A25, B10) in Thailand, was determined. They were classified as obligate (A17, B8) and possible (A21, B8) carriers by history taking. The phenotypic assessment was performed in two subsequent blood samples taken one week apart when they were not pregnant or on birth control pills. Then, molecular genetics among hemophiliac patients were performed. Inversion of intron 22 among 25 hemophilia A patients was initially performed. Then, the mutations were intensively detected by using conformation sensitive gel electrophoresis (CSGE). Coding region, intron/exon boun-daries, and 5′ and 3′ regions of the factor VIII and IX genes were amplified in 33 separate reactions in hemophilia A patients without inversion of intron 22 (n=10) and 9 separate reactions in hemophilia B patients (n=10). Samples displaying abnormal CSGE profiles were numbered according to Wood et al and Yoshitake et al. The results revealed that mutation were found at 88% (22/25, 15 inversion of intron 22 and 7 mutations) in hemophilia A and 90% (9/10) in hemophilia B patients. Ten were novel mutations as shown in Table 1. Also, the carrier state assessed by the phenotypic study and mutation detections are shown in Table 2. As a result, the phenotypic assessment alone showed a limitation in the diagnosis of carrier state especially hemophilia B carrier while the mutation detections provide an absolute diagnosis over phenotypic assessment.
Table 1. The identified ten novel mutations among Thai hemophilia A and B patients.
Table 2. Carrier state assessed by phenotypic study and mutation detections among females at risk.
Exon Nucleotide Amino acid FVIII:C/FIX:C (%) Promotor to exon 22 large deletion - FVIII:C < 1 6 680 G>A W208X FVIII: C = 2 8 1264 G>C D403H FVIII:C < 1 12 1820_1821 del CA 588 frame shift FVIII:C < 1 13 2066 T>G L670R FVIII:C = 1 14 4794 A>T E1579D FVIII:C = 1 21 6266 G>A W2070X FVIII:C < 1 A 57_58 del GA −37 frame shift FIX:C < 1 H 31127 T>G C336G FIX:C < 1 H 31171 T>G C350W FIX:C = 3.6 Type of carrier N FVIII:C or FIX:C < 50% FVIII:C/vWF:Ag < 0.6 Inversion intron 22 CSGE Total mutation Obligate hemophilia A 17 35.3% 70.6% 64.7% 17.6% 82.3% Obligate hemophilia B 8 12.5% - - 87.5% 87.5% Possible hemophilia A 21 19.0% 42.8% 33.3% 14.3% 47.6% Possible hemophilia B 8 25.0% - - - 62.5%
Thrombin, Fibrin Monomer and Factor XIII in Patients with Unexplained Intraoperative Bleeding.
Authors: Korte Wolfgang C. , Gabi Konrad , Gähler Anita , Schnider Thomas , Riesen Walter 
Published: October 2019

Abstract
To explore relevant changes in unexplained intraoperative bleeding, we evaluated elements of the final steps of the coagulation cascade in 226 consecutive patients undergoing elective surgery. Patients were stratified for the occurrence of unexplained intraoperative bleeding according to predefined criteria.
Twenty patients (8.8%) developed unexplained bleeding. Median intraoperative blood loss was 1350 ml (bleeders) and 400 ml (non-bleeders), p<0.001. Fibrinogen and factor XIII were more rapidly consumed in bleeders (p<0.001). Soluble fibrin formation (fibrin monomer) was elevated in bleeders throughout surgery (p < 0.014, table 1). However, F. XIII availability per unit thrombin generated was significantly decreased in bleeders pre-, intra- and postoperatively (p < 0.051). Computerized thrombelastography showed a parallel, significant reduction in clot firmness.
We suggest that a mild, pre-existing coagulopathy is not rare in surgical patients and probably can result in clinically relevant intraoperative bleeding. This haemostatic disorder shows impaired clot firmness, probably secondary to decreased cross-linking (due to a loss of F. XIII, both in absolute measures and per unit thrombin generated).
We are currently conducting a double blind, randomized trial on the use of F. XIII early during surgery. We suggest that the preoperative measurement of fibrin monomer concentration might allow preoperative risk stratification for intraoperative blood loss.
Fibrin Monomer is increased in “bleeders”
Non-Bleeder (FM median μg/l) Bleeder (FM median μg/l) p (Rank Sum test) T1 (preop) 7 18 <0.01 T2 (intraop) 6 14 <0.01 T3 (intraop) 9 20 0.014 T4 (postop) 26 52 <0.01 T5 (postop) 29 86 <0.01
Cost of Major Bleeding Following Major Orthopedic Surgery.
Authors: Oster Gerry , Vera-Llonch Montserrat , Hagiwara May 
Published: October 2019

Abstract
Rationale . The risk of major bleeding in major orthopedic surgery (MOS) patients who receive antithrombotics as prophylaxis against venous thromboembolism (VTE) may be higher for some agents than others. The cost of this complication is unknown.
Objective . To assess the impact of major bleeding following MOS on length of stay (LOS) and inpatient charges.
Methods . Using a database with information on ~750,000 admissions annually to 100+ US acute-care hospitals (MQProfile, Cardinal Information Corp.), we identified all patients who underwent MOS between 1/1/98 and 12/13/00. We stratified patients according to whether or not they experienced major postoperative bleeding prior to hospital discharge, defined as: (a) fatal bleeding; (b) nonfatal bleeding at critical site; (c) re-operation due to bleeding; and (d) overt bleeding with bleeding index (BI) ≥ 2, where BI = number of blood units transfused plus pre-bleeding minus post-bleeding hemoglobin (g/dL) values. LOS and total inpatient charges were compared between patients with and without major bleeding.
Results . 23,518 patients were identified who underwent MOS. Incidence of major bleeding was 2.6%. In multivariate analyses controlling for differences in baseline characteristics between patients with and without major bleeds, adjusted mean LOS was 1.8 days longer (95% CI: 1.5, 2.0) among the former (6.1 days vs 4.3 days for those without bleeds); adjusted mean total inpatient charges were $7,593 higher (95% CI: $6,622, $8,646) ($25,669 vs $18,076).
Conclusion . Major bleeding following MOS significantly increases LOS and hospital charges. The cost of major bleeding following MOS should factor into choice of VTE prophylaxis.