bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of an Adult Patient with Hemophilia A and High Titer Inhibitor with Rituximab and Prednisone.
Authors: Rose Shelonitda S. , Greenberg David B. , Maceron Francis , Pappas Heather , Parvin Saidi 
Published: April 2020

Abstract
Development of inhibitors is a serious complication in hemophilia A patients (factor VIII deficiency) who receive plasma-derived or recombinant products. It occurs in about 20–30% of patients with severe or moderate hemophilia A. The presence of a high titer inhibitor (titer &gt; 5BU), is associated with increased morbidity and mortality, complicates disease management, and increases cost of treatment. Treatments used for the management of acute bleeds include high doses of human FVIII, porcine FVIII, prothrombin complex concentrates, FVIII bypassing activity (FEIBA), and recombinant VIIa (rVIIa)). The induction of immune tolerance (IT)with daily high doses of FVIII has been reported to eradicate the inhibitor in 60–80% of patients; although it is a very costly procedure, the response appears to be dependent on the level of the inhibitor with patients with low inhibitor titer (&lt;10 BU) responding better to IT treatment. To rapidly reduce/eradicate the alloimmune factor VIII antibodies immunomodulatory agents, including immunoglobulin, corticosteroids, cyclophosphamide, azathioprine, and plasmapheresis have been used. Rituximab, an anti-CD20 monoclonal antibody, eliminates circulating B cells and has been shown to reduce/eradicate alloimmune factor VIII antibodies in children with severe hemophilia A. We report the clinical course and response to rituximab treatment in a 24 year old male with moderate hemophilia A and high titer inhibitor. The patient presented with a massive retroperitoneal bleed with Hb 6.4g/dL and an inhibitor titer of 41 BU reaching a maximum of 111 BU over the next four weeks. For the acute bleeding episode, he received FEIBA and rVIIa. For the treatment of inhibitor, he was given rituximab 375 mg/m2 × 4 together with prednisone 1 mg/Kg daily. Prednisone was slowly tapered off over the next several weeks. Three months later, his inhibitor titer had decreased to 35 BU and remained below 15 BU for the next 30 weeks. The course of this patient’s response suggests that rituximab in combination with prednisone may rapidly reduce inhibitor titer in adult patients with hemophilia and high titer inhibitor. It is possible the rituximab therapy may replace IT therapy or be used as an adjunct to IT therapy. Also, the combination of rituximab and prednisone treatment may reduce/prevent the exposure of young patients to cytotoxic chemotherapy. Randomized clinical trials will be required to determine whether the combination of rituximab and prednisone is a better option compared to cytoxan and prednisone to reduce/eradicate inhibitors in young adult hemophilia patients with high titer inhibitor.
Figure Figure
TFPI (Tissue Factor Pathway Inhibitor) Is Present in Breast Cancer Tumor Cells.
Authors: Sierko Ewa , Sawicki Zbigniew , Butkiewicz Adrianna , Zimnoch Lech , Kisiel Walter , Wojtukiewicz Marek 
Published: April 2020

Abstract
Abnormalities in hemostatic system are common in breast cancer patients. The principal initiator of blood coagulation activation in cancer patients is tissue factor (TF). Tissue factor plays an important role in the processes of angiogenesis, invasion and metastatic dissemination. Tissue factor pathway inhibitor (TFPI) is the main inhibitor of TF-dependent pathway of blood coagulation. The catalytic activity of the TF/VIIa complex triggers activation of factor X, consequently thrombin generation and finally fibrin formation. Thrombin and fibrin facilitate cancer progression. Previous immunohistochemical studies revealed no expression of TFPI in cancer cells of different malignant tumor types (Werling et al, Thromb Haemost1993; 69: 366–369) The aim of the study was to evaluate the expression of TFPI protein and mRNA in tumor cells of breast cancer.
Breast cancer tissues were obtained during surgical treatment of 35 women. The patients undergoing surgery had not received any previous anticancer therapy. Tumor fragments were preserved in 4% paraformaldehyde/phosphate buffered saline and than embedded in paraffin. Immunohistochemical studies (avidin-biotin complex-ABC - technique) were performed using polyclonal antibodies against TFPI. In situ hybridization method employed single-stranded DNA oligonucleotide (probe sequence: 5′Biotin-CATCGCCCAGTGCAGCCTCCGTCAG-Biotin3′) directed against locus NM 006287 of TFPI mRNA.
Strong expression of TFPI protein was observed in cancer cell bodies in examined specimens. Weak expression of the above protein was observed in tumor infiltrating macrophages. Normal cells revealed much weaker staining for TFPI than cancer cells. Similarly, mRNA for TFPI was observed in cancer cells of all breast cancer tissues.
The above data indicate that TFPI is present in neoplastic cells of breast cancer and may play a role in neutralizing TF procoagulant and signaling functions.
DDAVP Versus vWF-Containing Factor Concentrate in a Patient with ET Associated Acquired von Willebrand Syndrome (AVWS).
Authors: Kruse-Jarres Rebecca , Leissinger Cindy A. 
Published: April 2020

Abstract
The patient is a 16 year old boy with a past medical history of atrial septal defect and juvenile migraine headaches. He had no unusual bleeding or bruising during his early childhood including circumcision. His family history was negative for bleeding diasthesis. At the age of 12, he was diagnosed with an intramuscular hematoma on MRI after a baseball injury. Four months later he had heavy bleeding after an accidental knife wound to his hand, requiring repeated suturing. At age 14, he had another intramuscular hematoma after baseball injury, impairing range of motion in his leg. At age 15, following another deep muscular hematoma,, he underwent a laboratory evaluation for the first time. His CBC was normal except for a platelet count of 1,216,000/μl and he was subsequently diagnosed with ET. He had an elevated PTT, with a normal PT. He had a FVIII level of 42%, vWF Ag of 43%, and vWF:RCoF &lt; 20%. Multimer analysis showed relatively decreased to absent large multimers. To evaluate optimal treatment, a Stimate (DDAVP) challenge, as well as a vWF-containing concentrate (HumateP) infusion study were performed:
Stimate (DDAVP) trail Stimate (DDAVP) trail Humate P trail Humate P trail
The patient demonstrated a good response to DDAVP, with greater than 2-fold baseline levels of FVIII and VWF:RCo persisting after 4 hours. Multimer studies showed increases of low and intermediate multimers after administration of DDAVP. Following infusion of Humate P (53 vWF:RCo U/kg), VWF:Ag levels increased appropriately; however, VWF:RCo and FVIII levels increased to a lesser extent and fell to baseline by 4 hours. Platelet counts remained stable with both Stimate and Humate P. These results suggest that the patient’s platelets have an especially high affinity for high molecular weight (HMW) multimers, explaining the lack of HMW multimers on baseline analysis in this patient. The shortened response duration following Humate P infusion suggests rapid clearance due to platelet binding of the larger (and more functional) multimers contained in the concentrate. The longer duration of response to DDAVP, which releases his own low and intermediate multimers (but not HMW multimers) into circulation, indicates that DDAVP may be a superior treatment option in patients with AVWS associated with ET.
Increased Thrombin Generation Capacity in Septic Patients with DIC.
Authors: Kawasugi Kazuo , Shirasaki Ryousuke , Noguti MIzuho , Tashiro Haruko , Gotoh Moritaka , Shirafuji Naoki 
Published: April 2020

Abstract
Variety clinical conditions may cause systemic activation of coagulation, ranging from insignificant laboratory changes to severe disseminated intravascular coagulation (DIC). DIC consists of widespread systemic activation of coagulation, resulting in diffuse fibrin deposition in small and midsize vessels. However, little is known about thrombin generation capacity in patients with DIC. To investigate the thrombin generation capacity, we measured thrombin generation in septic patients with DIC (n=20) and acute promyelocytic leukemia (APL)-induced DIC (n=5). Thrombin generation was determined by the Throbogram-Thrombinoscope assay (Thermo Electron Corporation, Netherlands). The analyzed TG parameters ware the peak of thrombin activity (Peak) and endogenous thrombin potential (ETP).
The thrombin antithrombin complexes (TAT) levels were higher in both DIC patients as reported by others. In the septic patients with DIC, we found significant elevations in peak of thrombin activity and ETP as compared with normal controls (determined in 17 healthy males and 14 healthy female). However, the peak of thrombin activity and ETP levels were severely decreased by 60% n the APL patients with DIC. There was slightly correlation between the ETP and TAT levels in septic patients with DIC. Also, there was correlation between the ETP and bleeding tendency in APL patients with DIC.
These results suggest that assess of thrombin generation capacity may be helpful in the making the diagnosis in septic patients with DIC. It appears that assess of ETP may contribute to evaluate bleeding tendency in APL patients with DIC.
Sepsis with DIC APL with DIC Controls (n=31) *(P&lt;0.05) significantly different controls Peak (nM) 325.3 ± 55.5* 88.2 ± 47.2* 281.2 ± 40.9 ETP (nM.min) 1 ± 326.1* 652.1 ± 274.5* 1469.2 ± 227.3 TAT (μg/ml) 28.4 ± 17.5* 22.5 ± 15.3* &lt;3
Safety and Efficacy of Von Willebrand Factor/Factor VIII Concentrate (Humate-P®) for Prophylaxis of Excessive Bleeding during Elective Surgery in Patients with von Willebrand Disease.
Authors: Bernstein Jonathan , Gill Joan Cox , Leissinger Cindy A. , Di Paola Jorge , Ragni Margaret V. , Shopnick Rinah , Valentino Leonard A. , Friedman Carl , Knaub Sigurd ,   Humate P Study Group
Published: April 2020

Abstract
The safety, efficacy, and optimal dosing of a von Willebrand Factor/Factor VIII concentrate (Humate-P®) were evaluated in an open-label, uncontrolled study in patients with von Willebrand disease (VWD) undergoing elective surgery. During an initial pharmacokinetic (PK) phase, a detailed profile of FVIII:C, VWF:RCo, and VWF:AG was obtained for each patient after an infusion of 60 IU VWF:RCo/kg as Humate-P. Individual PK values were used to calculate subsequent loading and maintenance doses. Hemostatic efficacy was characterized using a 4-point scale (excellent, good, moderate/poor, or none) at several time points following surgery. Forty-two adults and children were enrolled in the study (17 VWD type 1; 6 type 2; 13 type 3; 6 type 2M), and 35 of these patients underwent a surgical procedure (classified as 3 oral, 7 minor, and 25 major). The median loading dose administered was 55.6 IU/kg (range 17.4 to 135.3 IU/kg). For patients with more severe VWD (baseline VWF:RCo&lt;12 IU/dL), the median loading dose administered was 70.9 IU/kg (range 38.6 to 135.3 IU/kg). The dosing interval was 8 or 12 hours in most subjects (4 were dosed every 6 hours), and treatment duration ranged from 1 to 6 days depending on surgery type. Effective hemostasis (investigator- rated as “excellent” or “good”) was noted in 91.4% (32/35) of subjects immediately after surgery, 100% (35/35) of subjects 14 days after surgery, and 100% (34/34) of subjects evaluated 24 hours after the last infusion (primary endpoint). Mean blood loss was less than expected, and four patients required transfusions, related to their surgery. Only six adverse events were considered possibly treatment related: headache (3), itching, nausea, and dizziness (1). These results demonstrate that von Willebrand Factor/Factor VIII concentrate is safe and effective in the prevention of excessive bleeding during and after elective surgery in adult and pediatric patients with von Willebrand disease.
Safety and Efficacy of Activated Recombinant FVII in Uncontrolled Bleeding Episodes.
Authors: Gunduz Eren , Akay Olga Meltem , Teke Hava Uskudar , Gulbas Zafer 
Published: April 2020

Abstract
Activated recombinant FVII (rFVIIa, NovoSeven) has been successfully used to control bleeding episodes in a variety of medical and surgical conditions including bleeding episodes secondary to over-anticoagulation, trauma, intracerebral hemorrhage, post operative bleeding and other refractory bleeding disorders. We report our experience in the use of rFVIIa to control bleeding episodes after failure of conventional measures.
A total of 5 patients (Behcet’s disease 1, over-anticoagulation with warfain and asprin 2, tuberculosis 1, and acute lymphoblastic leukaemia 1) were included in this analysis. The median age of the patients is 41. The bleeding episodes included massive hemoptysis 1, subdural hematoma 2, hemothorax and injury to intercostal artery following pleural biopsy 1 and cytomegalovirus-induced gastroenteritis in 1 patient. All patients failed to respond to conventional therapies prior to rFVIIa. The bleedings stopped with an average dose of 75 mcg/kg and with the average number of 2 doses of rFVIIa. No safety issues were encountered.
Conclusion: The use of rFVIIa is effective in the control of refractory bleeding episodes in patients with a variety of underlying medical or surgical conditions. In this small experience, a dose similar to that approved for patients with hemophilia and inhibitors appears to be effective to control bleeding within a short period of time after administration of rFVIIa. No safety issues were encountered in this group of patients. Further studies to evaluate the utility and appropriate dose and frequency of rFVIIa in refractory bleeding disorders are warranted.
JAK2 V617F in 3 Patients with Venous Thromboembolism (VTE) Followed during a Long Period of Time.
Authors: Conard Jacqueline , Marzac Christophe , Juin Fabrice , Horellou Marie-Helene , Calendini Ors’Antone , Casadevall Nicole 
Published: April 2020

Abstract
Hereditary thrombophilia and myeloproliferative disorders (MPD) are risk factors of VTE. The JAK2 V617F mutation may be found in polycythemia vera (PV), essential thrombocythemia (ET) and myelofibrosis. We report three women referred to our out-patient clinic for a thrombophilia screening. JAK2 mutation was studied using wild type FRET probes and subsequent analysis of the melting curve (James et al, Leukemia2006; 20: 350–353). Patient 1, 75 year-old (yo), had pulmonary embolism (PE) and proximal deep vein thrombosis (DVT) at 68. We detected heterozygous FV Leiden (FVL) and FII 20210A mutations. In 2005, she had internal jugular vein thrombosis after surgery (platelet count &gt; 600 G/L). ET was suspected in 2006. Patient 2, 44 yo, on oral contraception, had PE and proximal DVT at 33 after sclerotherapy, recurrent massive PE requiring emergency embolectomy and proximal DVT during pregnancy. Heterozygous FVL was detected in 1995 (platelet count was 432 G/L) and ET in 2000. Patient 3, 65 yo, with PV detected in 1995, had a proximal DVT one year later. Heterozygous FVL was detected. She is the only patient treated with hydroxyurea. Results of blood cell counts and JAK2 V617F/JAK2 WT ratios are shown in the table. Conclusion 1. JAK2 mutation was found in 3 patients with VTE, platelet count &gt;400 G/L and hereditary thrombophilia; 2. the risk of VTE related to JAK2 needs further investigation; 3. JAK2 V617F increased over time in 2 of 3 cases; 4. its early detection might improve the diagnosis and treatment of MPD and VTE.
Patient Year Platelet (G/L) Hemoglobin (g/dl) Hematocrit (%) Leukocytes (G/L) JAK2 ratio 1 2000 431 15.3 45.9 8.6 10%     2006 448 13.9 43.3 10.4 50% 2 1997 541 14.1 42.6 6.1 25% 2005 796 14.0 42.8 7.4 15% 3 1997 501 14.1 42.6 4.6 15% 2003 609 13.6 42.1 5.8 20% 2006 485 12.8 37.9 4.8 50%
Tumor Site and Metastases as Predictors of Venous Thromboembolism Recurrence among Active Cancer Patients with Incident Deep Vein Thrombosis or Pulmonary Embolism: A Population-Based Cohort Study.
Authors: Chee Cheng E. , Heit John A. , Ashrani Aneel A. , Petterson Tanya M. , Farmer Sara A. , Bailey Kent R. , Melton L. Joseph 
Published: April 2020

Abstract
Background: Active cancer is an independent predictor of recurrent venous thromboembolism (VTE; hazard ratio=2.2–4.2). However, whether the risk of VTE recurrence among active cancer patients can be further stratified by tumor site or presence of metastases is uncertain.
Objectives: To estimate and compare the cumulative incidence of VTE recurrence by tumor site and presence of metastases among active cancer patients with incident VTE.
Study Design and Population: Retrospective cohort study of Olmsted County, MN residents with active cancer who lived &gt;1 day after a first-lifetime deep vein thrombosis or pulmonary embolism over the 35-year period, 1966–2000 (n=418). 25 patients with oral (6), bone (1), skin (4), soft tissue (3), eye (1) and other/unknown (10) were excluded, leaving 393 remaining patients.
Measurements: Baseline demographic and clinical characteristics, tumor site, presence and location of tumor metastases, and date of first recurrent VTE. Tumor site and metastases were tested as potential predictors of time-to-recurrent VTE using the Cox proportional hazards model.
Results: 114 of 393 patients with active cancer developed recurrent VTE over 764 person-years of follow-up. The cumulative incidence of recurrent VTE at seven, 30, 90, and 180 days, 1, 5, and 10 years was 1.9%, 10.3%, 18.3%, 22.3%, 28.7%, 44.5%, and 53.5%, respectively. After adjusting for age and gender, tumor site was an independent predictor of first VTE recurrence (p&lt;0.01). The hazard of VTE recurrence was over 2-fold higher for lung cancer patients compared to the lowest recurrence group (kidney, bladder and other genitourinary cancer; HR=2.04, 95% CI: 0.88, 4.70, p=0.096), and the hazard for brain and pancreatic cancer was nearly 2-fold higher (HR=1.9 for each, p=0.22, 0.24, respectively). The hazard of recurrence among hematological; breast and ovarian; gastric, colon, and liver; and prostate cancer patients did not differ significantly from the lowest recurrence group. Univariately, the presence of metastases at cancer diagnosis was not associated with recurrent VTE (HR=1.16; 95% CI: 0.79, 1.69, p=0.45).
Conclusions: Tumor site is an independent predictor of VTE recurrence after adjusting for age and gender. In particular, lung, brain and pancreatic cancer patients have the highest risk for recurrence and these patients should be considered for secondary prophylaxis. Disease severity, as reflected by metastatic disease at cancer diagnosis, is not a predictor of recurrence.
Detection of Antiphospholipid Antibodies Using a Novel Multiplex Test Method: Correlation with ELISA Methods.
Authors: Janatpour Kim A. , Gosselin Robert C. , Owings John T. , Wun Ted 
Published: April 2020

Abstract
-Background: Laboratory criteria for the antiphospholipid antibody syndrome (APS) include detection of the lupus anticoagulant (LA) by coagulation based tests, or detection of either anti-cardiolipin (aCL), or anti-B2-glycoprotein I (aB2GPI) antibodies by enzyme-linked immunoabsorbant assay (ELISA). Multiplex testing enables simultaneous measurement of multiple serum antibodies with small beads coated with target antigens and small sample volumes (5 μL). We compared the concordance of a prototype multiplex method to standard ELISA methods for measuring IgG and IgM antibodies directed against CL or B2GPI.
Methods: Samples from patients with suspected APS were tested for IgG and IgM aCL and aB2GPI antibodies using standard ELISA methods (ELISA, Bio-Rad Laboratories, Hercules, CA) and by a prototype multiplex bead set analyzed on the BioPlex 2200 (Bio-Rad Laboratories, Hercules, CA). The multiplex method used beads coated with either CL alone, B2GPI alone, or CL-B2GPI complex. Results were normalized using ratios (obtained result/upper limit of normal). A positive result was defined as a ratio of &gt; 1. For CL, the multiplex test is considered positive if positive results are present using beads with either the CL alone or the CL-B2GPI complex.
Results:
Table 1. Concordance of ELISA vs Multiplex tests for antiphospholipid antibody detection Multiplex Test Results Concordance (%) ELISA Test Results Positive Negative Positive Negative All Results aCL-IgG Positive (n=52) 30 22 58 - Negative (n=232) 32 200 - 86 82 aCL-IgM Positive (n=42) 32 10 76 - Negative (n=241) 34 207 - 85 84 aβ2GPI-IgG Positive (n=34) 20 14 59 - Negative (n=249) 17 232 - 93 89 aβ2GPI-IgM Positive (n=61) 31 30 51 - Negative (n=219) 22 197 - 90 81
Conclusions: The overall concordance of multiplex results with ELISA results was good (81–89%). Negative multiplex results showed excellent correlation with ELISA (85–93%). Positive multiplex results had variable correlation with ELISA (51–76%). Evaluation of clinically significant positive results and clinical outcome measures is needed to determine clinical sensitivity and specificity of the multiplex test. Further refinement of the multiplex platform may provide an efficient and cost-effective assay for antibodies associated with the antiphospholipid syndrome.
Inactivation of Human White Blood Cells in Red Blood Cell Products Using Mirasol® Pathogen Reduction Technology (PRT).
Authors: Fast Loren D. , Marschner Susanne , DiLeone Gilbert , Doane Suzann K. , Goodrich Raymond P. 
Published: April 2020

Abstract
The transfusion of blood products can result in transmission of pathogens and immunological consequences such as transfusion associated graft-versus-host disease and alloimmunization. Previous studies have shown that exposure of platelet concentrates to riboflavin and light (Mirasol PRT treatment) causes irreparable modification of nucleic acids that results in inactivation of a wide range of pathogens as well as inhibition of the immunological responses mediated by the WBC present in platelet concentrates. Initial studies investigated the effects of Mirasol PRT treatment of RBC concentrates on WBC function. Human peripheral blood mononuclear cells (PBMNC) were purified by Ficoll-Hypaque discontinuous centrifugation from control or test non-leukoreduced RBC units exposed to riboflavin and varying doses of light. These PBMNC were tested for their ability to be activated in response to PMA, to proliferate in response to PHA or allogeneic stimulator cells, and to stimulate proliferative responses of allogeneic responder cells. While lower light doses were sufficient to inhibit activation and proliferation, higher energies (30J/ml RBC) were required for inhibition of antigen presentation. These Mirasol treatment conditions did not induce crossmatch incompatibility, methemoglobin (MetHb) levels stayed within an acceptable range (2.6% + 1.5) and hemolysis was below 1% during storage. Interestingly, MetHb levels decreased to background levels during storage at 4°C, suggesting that the activity of the enzyme NADH methemoglobin reductase was not compromised by the exposure to riboflavin and light. These treatment conditions also reduced levels of Gram positive and negative bacteria to the limits of detection and reduced infectivity of both enveloped and non-eveloped viruses by &gt; 4 logs on average in packed, washed RBC units. In summary, Mirasol PRT is able to functionally inactivate WBCs and pathogens in washed RBC products without adversely affecting the quality of the RBCs. This novel pathogen reduction therapy for RBC products complements the Mirasol PRT treatment for platelets and offers inactivation of pathogens in cellular blood components using a single technology.