bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein Z in Patients with Newly Diagnosed Multiple Myeloma
Authors: Oleksiuk Jolanta , Kloczko Janusz , Luksza Ewa , Galar Marzenna 
Published: April 2020

Abstract
Background Patients with multiple myeloma (MM) are relatively high risk of developing thromboembolic events. The pathogenesis of prothrombotic coagulation abnormalities in MM is not clear and probably of multifactorial origin. The deficiency of natural anticoagulant mechanisms, acquired resistance to protein C and reduced protein S function, has been described as one of the possible reason of hypercoagulable state in MM patients. Protein Z/Z-dependent protease inhibitor (PZ/ZPI) is a new anticoagulant system has been recently describe. PZ is a vitamin K-dependent protein which serves as cofactor for the ZPI that inactivates activated factor X, XI and IX by different mechanisms. Some reports suggest that protein Z deficiency might imbalance the haemostatic system with thrombotic consequences. However, to the best of our knowledge, no data are available regarding the potential role of protein Z in prothrombotic coagulation abnormalities in MM.
Aim: The aim of our study was to evaluate the plasma concentration of protein Z in relation to disease stage, type and levels monoclonal protein in patients with newly diagnosed untreated multiple myeloma.
Methods: The study population consisted of 41 patients (25 male, 16 female; median age: 63 years) with newly diagnosed untreated multiple myeloma. The presence of monoclonal serum immunoglobulin was found in 33 patients (25 and 8 with IgG and IgA paraprotein, respectively). The disease stage was evaluated according to Durie and Salmon criteria: 4 patients-stage I, 28 patients-stage II and 19 patients-stage III; in 8 of them abnormal renal function (serum creatinine value ≥2.0 mg/dl) was observed. The control group was formed by 19 healhty individuals with age and sex comparable with the patients. Protein Z plasma levels were measured using a commercial enzyme-linked immunosorbent assay (Asserachrom Protein Z; Diagnostica Stago, Asnieres) following the manufacturer’s instruction.
Results: The median protein Z plasma levels in patients with multiple myeloma and control subjects were similar. Median PZ levels were 1.45 ug/ml (range 0.27–3.17 ug/ml) in patients and 1.37ug/ml (range 0.34–1.96 ug/ml) in controls (p≥0.05). No significant correlation was found between protein Z plasma levels and disease stage, monoclonal serum immunoglobulin concentration, and renal function as well.
Conclusions: Our results suggest that protein Z is not an independent risk factor for thrombosis and does not play a significant role in the mechanism of thrombotic complication in patients with multiple myeloma.
Relationship Between Factor VIII Mutation and Inhibitor Development in Previously Treated Patients with Hemophilia a in Korea
Authors: Lee Kun Soo , Lee Soon Yong , Kook Hoon , Hwang Tai Ju , Choi Yong-Mook , Yoo Ki young , Jang In Jin 
Published: April 2020

Abstract
We reported the results of genetic analysis (factor VIII gene, interleukin-10, TNF-alpha) in 54 previously treated patients (PTPs, at least 100 exposure days or 1 year) including 18 with inhibitor history with severe hemophilia A in Korea. We confirmed 20 novel mutations among 35 different factor VIII mutations (intron 22 inversion, missense, deletion, nonsense and splicing), not reported by HAMSTeRS. As our patients were small group, it was not verified that relationship between factor VIII mutation and inhibitor incidence was statistically significant. 9 PTPs with inhibitor history had intron 22 inversion, 7 had missense, 3 had substitution, 1 had nonsense, 1 had small deletion and 1 had splicing. We did not find large deletion. 40 (74.1%) of 54 PTPs were found to have interleukin-10 (IL10) 134 bp microsatellite. IL10 134 bp microsatellite negative group showed statistically higher incidence of inhibitors (odds ratio (OR) 4.0, 95% confidence interval (CI) 1.12 – 14.35; P=0.047). No association was found between inhibitor formation and TNF-alpha gene. Inhibitors were identified in 88.9% of the patients with the TNF-alpha -308 G/G genotype, compared with 11.1% for the TNF-alpha -308 G/A genotype and 0% for the TNF-alpha -308 A/A genotype. Based on this report, prospective study with large sample size may lead to the development of preventive measures to minimize inhibitor formation.
Clinical Analysis of 22 Patients with Primary Fibrinolysis
Authors: Chen Qin-fen , Li Pei , Xie Yi , Chen Bao-An 
Published: April 2020

Abstract
Objective: To analysis the clinical features and therapy of acquired primary fibrinolysis.
Methods: The underlying diseases, clinical manifestations, laboratory findings, treatment and outcomes of 22 primary fibrinolysis were analyzed retrospectively.
Results: 22 patients were enrolled, 13 were male, and 9 were female. The median age was 54.9(17–77) years. The underlying diseases were ulcer of gastric-carcinoma bleeding, colorectal polypectomy by endoscope, intracranial tumor to get worse quickly, metanephric duct galeted by holmium laser+DJ tube implantation, herniorrhaphy of abdominal incision, gaster carcinosectomy, colon carcinosectomy, cerebral trauma and operation of cranium. Patients have bleeding and hemorrhage from surgical incisions or venipuncture or catheter sites in 1 to 7 days after trauma or surgery, with a disproportionately low level of fibrinogen (Fg), high level of tissue type plasminogen activator activity (t-PA) and a relatively normal of thrombin time (PT), activated partial thromboplastin time (APTT), thrombin time(TT), normal or nearly normal of platelet count. Diagnosis of primary fibrinolysis was established clearly, the patients were treated with plasma, cryoprecipitate, fibrinogen and fibrinolytic inhibitor PAMBA. Prognosis was quite good, 18/22 patients were cured.
Conclusion: Primary fibrinolysis may complicate various disorders, most of them are trauma, surgery, and malignancy. Bleeding and hemorrhage from surgical incisions or venipuncture or catheter sites is a predominant clinical feature. Low fibrinogen level with a normal or nearly normal platelet count is a predominant laboratory feature. We should differentiate primary fibrinolysis from the secondary fibrinolysis in DIC. Control of the primary disease, use fibrinolytic inhibitor, and replace depleted clotting factors with plasma, cryoprecipitate, fibrinogen, most of patients can be cured.
Winrho: Safety and Efficacy during Pregnancy
Authors: Cromwell Caroline , Tarantino Michael , Aledort Louis M. 
Published: April 2020

Abstract
Anti-D (WinRho SDF Baxter) immune globulin is approved in the United States for the treatment of chronic and acute ITP in adult and children. It is also approved for the suppression of Rh isomimmunization in pregnant women. The use of Anti-D for ITP during pregnancy is not licensed in the United States. In pregnant patients in particular, treating physicians are wary of the use of a drug in an off-label setting given the fear of increased risk to the mother and fetus. To assess its use in pregnant patients a surveillance questionnaire was sent to over 700 practicing adult or pediatric hematologists and obstetricians in the United States. A computer based literature search using the search terms “ITP and pregnancy” and “Anti-D and pregnancy” was also conducted.
Patient Age Gestational Age Number of doses Concomitant meds Maternal Platelet Response* Maternal adverse events Fetal adverse events *Response is defined as a platelet count greater than 30,000 1 35 38 1 Unknown Y N N 2 28 15 7 Y Y Y N 3 23 38 1 Y Y N N 4 36 38 1 N Y N N 5 36 34 1 Y Y N N 6 37 14 4 Unknown Y Y N 7 37 37 1 N Y Y Y 8 31 36 1 Y Y Y N 9 46 20 1 Y Y N N 10 38 37 2 Y Y N N
Very few pregnant patients with ITP appear to have been treated with Anti-D. Information on 10 cases were obtained for review related to the efficacy and safety of Anti-D to mother and child.
Maternal Adverse Events included: headache (2 patients), nausea (1 patient), hemolysis (1 patient), and myalgias (1 patient). Fetal adverse events included fetal jaundice in one child. Concomitant medications included prednisone and IVIG.
A majority of these patients were treated during the third trimester of pregnancy. Out of the 10 patients, all patients achieved a platelet count greater than 30,000. Many of these patients were on concomitant medications for ITP, and were initiated on Anti-D in an attempt to raise the platelet count. There were no episodes of DIC, renal failure, fetal death, neonatal hemolysis or spontaneous abortion. One child had jaundice, which resolved with phototherapy and there was no long-term sequelae. This review provides some data for the efficacy and safety of anti-D for pregnant patients with ITP. Further investigation of its use during pregnancy is on-going. These data should encourage larger studies so this indication can be considered for approval
A SCID Mouse Model for Monitoring in Vivo Viability of Human Platelet Concentrates Using Flow Cytometry
Authors: Ding Jia-hua , Huang Cheng-yin , Xu Shiyun 
Published: April 2020

Abstract
Objective To develop an animal test method for evaluating the in vivo quality of human platelet concentrates.
Methods Human platelets were transfused to mice by tail vein with a 1mL insulin syring fitted with a 29-gauge ultra-fine needle. Blood samples were taken at 30 minutes,2,4,6,8,12, and 24hours after infusion with a tail vein nick technique, whole blood was collected into heparinized capillary tubes. Human platelets in mouse whole blood were detected by flow cytometry with monoclonal anti-human CD61-PE–conjugated antibodies. All subsequent recoveries were calculated as a percentage of the initial collection.
Results The survival time of human platelets were significantly prolonged in SCID than in BALB/c,FVB mice. Recoveries at 4 hours after transfusion in SCID, BALB/c,FVB mice were 68.6%±8.1%(n =10),29.9%±6.5%(n =8),28.1%±5.5%(n =8), respectively, and with a T½ estimate of 8 hours for SCID, 2.5 hours for BALB/c and 2 hours for FVB mice. platelet storage lesions either by chemical treatment or by suboptimal conditions storage exhibited decreased recoveries in SCID mice.
Conclusion The quality of platelet Products can be evaluated by assessing the survival of human platelets in SCID mice using flow cytometry.
Immature Platelet Fraction (IPF) as Novel Laboratory Parameter for Managing Early Onset Thrombocytopenia in Very Low Birth Weight Infants
Authors: Weimann Andreas , Lun Andreas , Gaedicke Gerhard , Cremer Malte 
Published: April 2020

Abstract
Thrombocytopenia (platelet count &lt;150/nl) is one of the most common hematologic problems in preterm and term neonates and affects 18 to 35% of all patients admitted to neonatal intensive care units (NICU). Thrombocytopenia is more than twice common in extremely low birth weight infants (ELBW; &lt;1000g) as reported among the general NICU population. Among thrombocytopenic ELBW infants almost 40% suffer from severe thrombocytopenia as defined by a platelet count &lt;50nl. The risk for hemorrhage, which may cause acute life-threatening complications and/or life-long disability in more than 15%, is difficult to assess, because it is closely related to the gestational and postnatal age of the neonate as well as the cause of the thrombocytopenia and the severity of concurrent conditions. From routine full blood counts of premature (birth weight &lt;1500g) and full term babies we additionally determined platelet counts, IPF, MPV, NRBC and reticulocyte counts. On the basis of individual IPF and platelet counts we were able to predict the platelet counts of the following day. In non-thrombocytopenic preterm and term neonates no significant changes in IPF values were found during the first week of life. In the first week, thrombocytopenic neonates displayed higher IPF values than neonates with normal plaletet counts. We hypothesize that IPF is higher in neonates with chronic hypoxia as leading cause for thrombocytopenia and lower in case of perinatal infections. IPF could be a novel parameter in routine diagnostics available at a 24/7 basis in VLBW infants and may be valuable in identifying the underlying pathomechanism of various thrombocytopenias and in clinical decision making on platelet transfusions.
TTP, ET, and ITP Sequential Occurrence in a Single Patient: a Case Report
Authors: Farhat Mirna H , Hanbali Amr 
Published: April 2020

Abstract
INTRODUCTION: Thrombotic thrombocytopenic purpura (TTP), essential thrombocythemia (ET) and idiopathic thrombocytopenic purpura (ITP) are three separate disease entities that affect the platelets. Each has a different pathophysiology clinical presentation and consequences. We present a case where TTP, ET, and ITP were diagnosed in the same patient at different times of her clinical course with the aim of drawing the attention to this undocumented occurrence which remains under investigation.
CASE REPORT: A 42 year old African American female was diagnosed in 1994 with TTP after she presented with slurring of speech and left upper extremity weakness. Her hemoglobin was 9.7 g/dL, creatinine of 1.3 mg/dL, LDH of 448 IU/L and her peripheral smear showed schistocytes. She was diagnosed with TTP and was treated with plasma exchange with improvement in the platelet count. In March 2001, she presented with purple toe syndrome and a platelet count of 877,000. Bone marrow biopsy revealed panmyeloid hyperplasia, clustering of megakaryocytes, and stainable iron. She was then diagnosed to have essential thrombocythemia and was started on Anagrelide, which was later switched to Hydroxyurea. In October 2001, Hydroxurea was stopped and two weeks later, her platelet count dropped to 12,000. Investigations including a bone marrow biopsy were done which showed megakaryocytes in atypical clusters. No schisocytes were seen on peripheral smear. The patient’s platelet count dropped to 7,000 and she was transfused with 12 units of platelets. Post transfusion her count was 90,000 but dropped to 25,000 in less than 12 hours. She was then started on IV immunoglobulins and steroids for a presumptive diagnosis of ITP and her platelet count subsequently improved. Subsequent outpatient evaluation was negative for ANA, C3, C4, and HIV
CONCLUSION: The fact that both immune and thrombotic thrombocytopenic purpura occur with increased frequency among persons with systemic lupus erythematosus, HIV disease, or pregnancy supports the hypothesis that some pathophysiologic factors are shared. As the three conditions have different natural histories and require different treatment modalities, it is important to recognize that these diseases may be seen sequentially and here comes the importance of reviewing peripheral blood smears for evaluation of thrombocytopenia and bone marrow aspirations for diagnosis of thrombocythemia in order to reach an accurate diagnosis and tailor therapy accordingly. This case demonstrates the variability and complexity of platelet disorders. Platelets may go one way or another and can even go in opposite directions in the same person. After reviewing the literature, there are no reported cases of TTP, ET, and ITP diagnosed in the same patient. Our aim is to draw the attention to this rare case which is still under investigation.
Invasive Streptococcus Pneumoniae infection Associated with Hemolytic Uremic Syndrome in Chinese Pediatric Patients
Authors: So Jason Chi Chiu , Leung Yuk-Yan , Yip Sze Fai , Lam Clarence CC , Chan Li Chong 
Published: April 2020

Abstract
Hemolytic uremic syndrome (HUS) associated with pneumococcal pneumonia is rarely reported in the Western literature, in contrast to classical HUS associated with Escherichia coli (E. coli) (O157:H7). We conducted a retrospective review over a 2-year period from 2006 to 2008 in a large tertiary teaching hospital. Five cases were identified. All patients were Chinese children with a median age of 3 years (range: 2 – 4 years). No documented case of E. coli (O157:H7) infection was seen in the same hospital over the past 5 years from 2003 to 2008. Streptococcus pneumoniae (S. pneumoniae) infection was confirmed by positive blood and/or pleural fluid culture. Four of 5 patients developed empyema requiring decortication. HUS was diagnosed as early as 3 days after onset of febrile illness and was apparent within 2 weeks in all patients. The mean nadir for hemoglobin and platelet was 41 g/L (range: 13 – 55 g/L) and 7 ×109/L (range: 4 – 9 ×109/L), respectively. None of them had significant bleeding. All patients received red cell transfusion and 4 of 5 patients received platelet transfusion for prophylaxis or for coverage of invasive procedures. T activation on red cells was documented in all cases. Washed red cells and concentrated pooled platelet-rich plasma were transfused, except for 1 case when transfusion took place before a diagnosis of HUS was made. All patients had impaired renal function as evident by a raised serum creatinine level (range: 101– 756 umol/L). Only 1 patient required dialysis. One patient deteriorated rapidly and died of refractory septicemic shock and multi-organ failure 30 hours after admission. Her hemoglobin and platelet on admission was 106 g/L and 115 ×109/L, respectively. She received unwashed red cells and ordinary platelet concentrate upon clinical deterioration. Blood smear examination and T activation study subsequently confirmed a diagnosis of S. pneumoniae associated HUS. All surviving patients had full renal and hematological recovery with a median follow up of 11 months (range: 3 – 28 months). Invasive S. pneumoniae infection is a relatively common association in Chinese pediatric patients with HUS. This condition can be fatal in the acute state but the medium to long term prognosis is favorable. Transfusion of washed red cells and plasma-reduced platelets is a routine practice in this group of patients, although the efficacy and necessity of this practice has not been formally studied.
Early Hb Response to ESA Treatment May Be An Indicator of Better Survival Prognosis
Authors: Berlin Jesse A , Bowers Peter , Rao Sudhakar , Aravind Suresh , Sun Steven , Liu Kevin 
Published: April 2020

Abstract
Chemotherapy induced anemia patients who respond to ESA treatment have hemoglobin increases within 4–8 weeks. Patients with inadequate Hb response after several weeks treatment often have their ESA dose escalated.. We conducted an exploratory analysis to test the hypothesis that safety outcomes in randomized studies of epoetin alfa might differ depending on the Hb response after 4–8 weeks of treatment.
Methods: The analysis compared the survival across subsets of epoetin-alfa treated patients. Specifically, a landmark analysis was used, which defines a hemoglobin responder at a pre-specified point in time (in this case 4 & 8 weeks post treatment), and then examines survival subsequent to that point in time.Patients were categorized as “Hb responder” when their Hb increased by &gt;0.5 g/dL; “Hb stable” when Hb change within ≤ 0.5g/dL; “Hb non-responder” when the Hb decreased &gt;0.5 g/dL, compared to the value prior to epoetin-alfa treatment. Survival was estimated using the Kaplan-Meier method and comparisons were made between the responders and non-responders versus the stable group. Cox’s proportional hazards model was used to adjust for the following baseline covariates: hemoglobin prior to treatment, baseline performance status, and advanced disease at baseline. All analyses were stratified by study to account for any differences in the study populations and study conduct.
Results: These exploratory findings suggest the possibility that patients identified as non-responders to ESAs after 4 or 8 weeks of ESA treatment may be at increased risk of death, and that this effect is most pronounced in the studies that treated patients beyond the correction of anemia. Although these analyses were adjusted for several key baseline covariates, it is unclear whether these effects result from treatment, or whether patients who fail to respond to epoetin alfa are inherently at increased risk of death (e.g., due underlying malignancy), regardless of their treatment status.
Costimulatory Blockade Enhances Engraftment and Prevents Anti-Donor Antibody Generation in Nonmyeloablative Conditioned Prediabetic NOD Mice
Authors: Bozulic Larry D , Xu Hong , Huang Yiming , Ildstad Suzanne T 
Published: April 2020

Abstract
Chimerism induces tolerance to organ and tissue grafts. Although the toxicity of conditioning has been significantly reduced with nonmyeloablative approaches, it would be beneficial to further reduce the intensity of conditioning in organ transplant recipients. Studies in normal mice and autoimmune NOD mice have revealed that the primary role for conditioning is to control host-versus-graft alloreactivity, allowing for immune-based conditioning to establish chimerism. Recent insights into the mechanism of interaction and crossregulation between innate and adaptive immune responses have led to the development of new approaches for immune-based conditioning. We previously demonstrated that preconditioning of diabetes-prone NOD mice with anti-CD8 monoclonal antibody (mAb) combined with anti-CD154 mAb allowed chimerism to be established with 550 cGy total body irradiation (TBI). Here we investigated whether combined costimulatory blockade can improve the nonmyeloablative regimen and enhance bone marrow chimerism in autoimmune recipients. Prediabetic NOD (H-2d) mice were treated with anti-CD8 antibody (day -3). After 500 cGy TBI (day 0), recipient NOD mice were transplanted with 30 × 106 B10.BR (H-2k) bone marrow cells (day 0) and received anti-CD154, anti-OX40L, and anti- inducible co-stimulatory molecule (ICOS) mAbs intraperitoneally (IP) (day 0, 1, 2, 3). Chimerism and multilineage analysis were quantitated by flow cytometry. Chimeric animals produced multilineage donor chimerism. While 18 prediabetic NOD mice demonstrated an average PB chimerism of ~37% at 1 month and 61% engraftment, 15 of 18 mice lost PB chimerism by 6 months. NOD mice were then transplanted with B10.BR donor skin grafts 1 month post BM transplant. Flow cytometry cross-match assays were performed to detect anti-donor antibody (Ab) in the sera collected 1 month post skin grafting. 44% of chimeric NOD mice (n=9) accepted their skin grafts for over 90 days, while 100% of non-chimeric animals (n=4) rejected their grafts within 60 days. NOD mice transplanted with B10.BR skin grafts alone rejected their grafts within 2 weeks and generated significantly higher levels of donor-specific Abs (mean fluorescence intensity: 251.2 ± 61.5, P&lt;0.0001, n=6) compared to chimeric NOD (4.5 ± 0.6, P&lt;0.0005, n=17) or non-chimeric NOD (12.6 ± 2.4, P&lt;0.0005, n=10). Both chimeric NOD and non-chimeric NOD mice transplanted with 3rd party B6 skin grafts rejected their grafts within 30 days. These results suggest that rejection of skin grafts in chimeric and nonchimeric animals is not associated with anti-donor antibody generation in preconditioned animals. Studies are currently underway to determine if impaired generation of effector/memory T cells (CD44high/CD62Llow/−) is responsible for enhanced engraftment and to determine the potential mechanisms that promote tolerance in prediabetic NOD mice after loss of PB chimerism.