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https://www.readbyqxmd.com/read/27913544/treatment-of-rare-factor-deficiencies-in-2016
#1
Flora Peyvandi, Marzia Menegatti
Rare bleeding disorders (RBDs) are a heterogeneous group of coagulation disorders characterized by fibrinogen, prothrombin, factors V, VII, X, XI, or XIII (FV, FVII, FX, FXI, or FXIII, respectively), and the combined factor V + VIII and vitamin K-dependent proteins deficiencies, representing roughly 5% of all bleeding disorders. They are usually transmitted as autosomal, recessive disorders, and the prevalence of the severe forms could range from 1 case in 500 000 for FVII up to 1 in 2-3 million for FXIII in the general population...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913543/hemophilia-and-inhibitors-current-treatment-options-and-potential-new-therapeutic-approaches
#2
Shannon L Meeks, Glaivy Batsuli
The immune response to infused factor concentrates remains a major source of morbidity and mortality in the treatment of patients with hemophilia A and B. This review focuses on current treatment options and novel therapies currently in clinical trials. After a brief review of immune tolerance regimens, the focus of the discussion is on preventing bleeding in patients with hemophilia and inhibitors. Recombinant factor VIIa and activated prothrombin complex concentrates are the mainstays in treating bleeds in patients with inhibitors...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27909693/unfractionated-and-low-molecular-weight-heparin-and-the-phosphodiesterase-inhibitors-ibmx-and-cilostazol-block-ex-vivo-equid-herpesvirus-type-1-induced-platelet-activation
#3
Tracy Stokol, Priscila B D Serpa, Muhammad N Zahid, Marjory B Brooks
Equid herpes virus type-1 (EHV-1) is a major pathogen of horses, causing abortion storms and outbreaks of herpes virus myeloencephalopathy. These clinical syndromes are partly attributed to ischemic injury from thrombosis in placental and spinal vessels. The mechanism of thrombosis in affected horses is unknown. We have previously shown that EHV-1 activates platelets through virus-associated tissue factor-initiated thrombin generation. Activated platelets participate in thrombus formation by providing a surface to localize coagulation factor complexes that amplify and propagate thrombin generation...
2016: Frontiers in Veterinary Science
https://www.readbyqxmd.com/read/27904905/idarucizumab-does-not-have-procoagulant-effects-assessment-of-thrombosis-biomarkers-in-healthy-volunteers
#4
Michael Schmohl, Stephan Glund, Akiko Harada, Susumu Imazu, Marina De Smet, Viktoria Moschetti, Steven Ramael, Ippei Ikushima, Fredrik Grünenfelder, Paul Reilly, Joachim Stangier
Idarucizumab, a humanised monoclonal antibody fragment, binds dabigatran with high affinity and immediately, completely and sustainably reverses dabigatran-induced changes on blood coagulation. The present analysis focuses on the evaluation of potential procoagulant properties of idarucizumab when administered in the absence of dabigatran. As part of two Phase I studies conducted in healthy Caucasian and Japanese male volunteers, the effect of idarucizumab (8 g as a 1-hour [h] infusion and 4 g as a 5-minute [min] infusion) and placebo on calibrated automated thrombography (CAT) was assessed using platelet-poor plasma samples...
December 1, 2016: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/27902939/factor-xiii-deficiency-enhances-thrombin-generation-due-to-impaired-fibrin-polymerization-an-effect-corrected-by-factor-xiii-replacement
#5
Hanna H Pitkänen, Annukka Jouppila, Marja Lemponen, Minna Ilmakunnas, Jouni Ahonen, Riitta Lassila
INTRODUCTION: Factor XIII (FXIII) cross-links fibrin, completing blood coagulation. Congenital FXIII deficiency is managed with plasma-derived FXIII (pdFXIII) or recombinant FXIII (rFXIII) concentrates. AIM: As the mechanisms protecting patients with low FXIII levels (<5IU/dL) from spontaneous bleeds remain unknown we assessed the interplay between thrombin generation (TG), fibrin formation and clot kinetics before and after FXIII administration in three patients with FXIII deficiency...
November 16, 2016: Thrombosis Research
https://www.readbyqxmd.com/read/27900155/normal-platelet-function-in-platelet-concentrates-requires-non-platelet-cells-a-comparative-in-vitro-evaluation-of-leucocyte-rich-type-1a-and-leucocyte-poor-type-3b-platelet-concentrates
#6
William R Parrish, Breana Roides, Julia Hwang, Michael Mafilios, Brooks Story, Samir Bhattacharyya
BACKGROUND: Therapeutic success of platelet-rich plasma (PRP) may vary based on the composition and preparation method. The objective of this study was to evaluate the cellular components of platelet concentrates produced by a leucocyte-rich (LR-PRP) and a leucocyte-poor PRP systems (LP-PRP). METHODS: Parameters evaluated included platelet recovery, platelet concentration, red blood cell (RBC) and white blood cell (WBC) composition, platelet growth factor release and stimulation of human tendon cell proliferation in vitro...
2016: BMJ Open Sport & Exercise Medicine
https://www.readbyqxmd.com/read/27899993/predictive-value-of-microparticle-associated-tissue-factor-activity-for-permeability-glycoprotein-mediated-multidrug-resistance-in-cancer
#7
Antonio Angelini, Sebastiano Miscia, Maria Antonietta Centurione, Roberta Di Pietro, Lucia Centurione
Multidrug resistance (MDR) protein 1, which is also known as permeability glycoprotein (Pgp), and tissue factor (TF) are recurrently overexpressed on the surface of cancer cells, likely in response to stimuli such as chemotherapy. Microparticles (MPs) released from cancer cells into the bloodstream express tumour markers on their surface that may be useful as predictive biomarkers for evaluating disease progression. The present study measured the level of TF/factor VII (FVII)-dependent coagulation of MPs isolated from the plasma of cancer patients with various tumours, who were undergoing chemotherapy...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27898483/reply-to-thrombin-generation-tests-and-viscoelastic-testing-in-cirrhosis-comparing-apples-and-oranges
#8
Claude Lentschener, Claire Flaujac, Isabelle Gouin-Thibault, Charles Marc Samama
No abstract text is available yet for this article.
January 2017: European Journal of Anaesthesiology
https://www.readbyqxmd.com/read/27898482/thrombin-generation-tests-and-viscoelastic-testing-in-cirrhosis-comparing-apples-and-oranges
#9
Susan Mallett, Paolo Simioni, Klaus Görlinger, Christian Fenger-Eriksen
No abstract text is available yet for this article.
January 2017: European Journal of Anaesthesiology
https://www.readbyqxmd.com/read/27894747/reduction-of-coagulability-state-one-year-after-bariatric-surgery
#10
Jérémie Thereaux, Fanny Mingant, Charles Roche, Hubert Galinat, Francis Couturaud, Karine Lacut
BACKGROUND: Obese patients are in a hypercoagulable state relative to normal-weight patients. Low-grade inflammation may be a key factor for this condition. OBJECTIVES: Our study aimed to compare the coagulability state of morbidly obese patients before and 1 year after bariatric surgery (BS) using the Thrombin Generation (TG) test, a validated method to assess coagulation in vitro. SETTING: University hospital. METHODS: All patients undergoing BS between September 1, 2014 and April 30, 2015 were eligible for this prospective study (n = 42)...
October 1, 2016: Surgery for Obesity and related Diseases: Official Journal of the American Society for Bariatric Surgery
https://www.readbyqxmd.com/read/27891624/quarantine-versus-pathogen-reduced-plasma-coagulation-factor-content-and-rotational-thromboelastometry-coagulation
#11
Oliver M Theusinger, David Goslings, Jan-Dirk Studt, Brigitte Brand-Staufer, Burkhardt Seifert, Donat R Spahn, Beat M Frey
BACKGROUND: Different types of fresh-frozen plasma (FFP) exist, and the concentrations of plasma proteins vary between individuals and blood groups. Furthermore, processing may also influence the content. Quarantine-stored plasma (qFFP) and plasma that was pathogen-reduced using blood-safety (Intercept) technology (piFFP) were analyzed regarding procoagulant and anticoagulant hemostasis proteins, including endogenous thrombin (thrombin-generation) potential (ETP). MATERIALS AND METHODS: Thirty-five samples of each type of FFP were analyzed using only male Blood Group O donors...
November 27, 2016: Transfusion
https://www.readbyqxmd.com/read/27886531/coagulation-and-sepsis
#12
REVIEW
Marcel Levi, Tom van der Poll
Severe sepsis is almost invariably associated with systemic activation of coagulation. There is ample evidence that demonstrates a wide-ranging cross-talk between hemostasis and inflammation, which is probably implicated in the pathogenesis of organ dysfunction in patients with sepsis. Inflammation not only leads to initiation and propagation of coagulation activity, but coagulation also markedly influences inflammation. Molecular mechanisms that play a role in inflammation-induced effects on coagulation have been recognized in much detail...
November 19, 2016: Thrombosis Research
https://www.readbyqxmd.com/read/27885373/a-new-era-of-treatment-for-patients-with-haemophilia-a
#13
Robert Klamroth
Treatment and prevention of bleeding episodes in patients with severe haemophilia A require frequent intravenous injection of factor VIII. Inhibitory antibodies against factor VIII occur in approximately 30 % of these patients during the first exposure days and immune tolerance induction to eradicate the inhibitor is challenging. Prevention of bleeds in patients with haemophilia A and inhibitors is less effective and there is ongoing research for alternative treatment options. A promising approach in 2016 is the development of emicizumab (ACE910), a bi-specific IgG antibody to factor IXa and factor X, that mimics the cofactor function of factor VIII...
November 25, 2016: Hämostaseologie
https://www.readbyqxmd.com/read/27884512/design-synthesis-and-antithrombotic-evaluation-of-novel-non-peptide-thrombin-inhibitors
#14
Dongxing Chen, Jinyu Shi, Jing Liu, Xueying Zhang, Xiaoying Deng, Yanyan Yang, Shuang Cui, Qihua Zhu, Guoqing Gong, Yungen Xu
Ten derivatives of 4-((1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazin-1-yl)methyl)benzimida-mide (I-1∼I-2, II-1∼II-8) were designed, synthesized and evaluated for their inhibitory effect on human thrombin. Compound II-7 (IC50=82.8nM), which showed the strongest thrombin inhibitory activity among the tested compounds, was chosen as the lead compound, and ten carbamate derivatives (II-9a∼II-13a, II-9b∼II-12b, II-14) were prepared and evaluated for their anticoagulant activity. The results indicate that most of the tested compounds exhibit a certain degree of inhibitory effect on thrombin-induced platelet aggregation, among which compounds II-11a (IC50=8...
November 9, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27882572/a-paired-comparison-of-thawed-and-liquid-plasma
#15
Lucy Backholer, Laura Green, Sian Huish, Sean Platton, Michael Wiltshire, Heidi Doughty, Elinor Curnow, Rebecca Cardigan
BACKGROUND: To make plasma readily available to treat major hemorrhage, some centers are internationally using either thawed plasma (TP) or "never-frozen" liquid plasma (LP). Despite the routine use of both, there are limited data comparing the two. The hemostatic properties of LP were evaluated and compared to TP in a paired study. STUDY DESIGN AND METHODS: Two ABO-matched plasma units were pooled and split to produce 1 unit for LP and 1 unit for TP. Samples of TP and LP, stored at 2 to 6°C, were tested for a range of coagulation factors, thrombin generation, and rotational thromboelastometry...
November 23, 2016: Transfusion
https://www.readbyqxmd.com/read/27876270/a-new-manufacturing-process-to-remove-thrombogenic-factors-ii-vii-ix-x-and-xi-from-intravenous-immunoglobulin-gamma-preparations
#16
Dong Hwarn Park, Gil Bu Kang, Dae Eun Kang, Jeung Woon Hong, Min Gyu Lee, Ki Yong Kim, Jeung Whan Han
Coagulation factors (II, VII, IX, X, and particularly XIa) remaining in high concentrations in intravenous immunoglobulin (IVIG) preparations can form thrombi, causing thromboembolic events, and in serious cases, result in death. Therefore, manufacturers of biological products must investigate the ability of their production processes to remove procoagulant activities. Previously, we were able to remove coagulation factors II, VII, IX, and X from our IVIG preparation through ethanol precipitation, but factor XIa, which plays an important role in thrombosis, remained in the intermediate products...
November 18, 2016: Biologicals: Journal of the International Association of Biological Standardization
https://www.readbyqxmd.com/read/27875570/towards-a-tissue-engineered-contractile-fontan-conduit-the-fate-of-cardiac-myocytes-in-the-subpulmonary-circulation
#17
Daniel Biermann, Alexandra Eder, Florian Arndt, Hatim Seoudy, Hermann Reichenspurner, Thomas Mir, Arlindo Riso, Rainer Kozlik-Feldmann, Kersten Peldschus, Michael G Kaul, Tillman Schuler, Susanne Krasemann, Arne Hansen, Thomas Eschenhagen, Jörg S Sachweh
The long-term outcome of patients with single ventricles improved over time, but remains poor compared to other congenital heart lesions with biventricular circulation. Main cause for this unfavourable outcome is the unphysiological hemodynamic of the Fontan circulation, such as subnormal systemic cardiac output and increased systemic-venous pressure. To overcome this limitation, we are developing the concept of a contractile extracardiac Fontan-tunnel. In this study, we evaluated the survival and structural development of a tissue-engineered conduit under in vivo conditions...
2016: PloS One
https://www.readbyqxmd.com/read/27865966/febuxostat-attenuates-paroxysmal-atrial-fibrillation-induced-regional-endothelial-dysfunction
#18
YanGuang Li, FuKun Chen, Long Deng, Kun Lin, Xiangmin Shi, Shan Zhaoliang, YuTang Wang
BACKGROUND: Paroxysmal atrial fibrillation (PAF) can increase thrombogenesis risk, especially in the left atrium (LA). The exact mechanism is still unclear. OBJECTIVE: We assessed the effects of PAF on endothelial function, and investigated if febuxostat (FX) can attenuate endothelial dysfunction by inhibition of xanthine oxidase (XO). MATERIALS AND METHODS: Eighteen male New Zealand white rabbits were divided randomly into sham-operated (S), PAF (P) or FX+pacing (FP) groups...
November 11, 2016: Thrombosis Research
https://www.readbyqxmd.com/read/27865782/application-of-nano-lc-maldi-tof-tof-ms-for-proteomic-analysis-of-microvesicles
#19
Joanna Kasprzyk, Ewa Stępień, Wojciech Piekoszewski
Activated platelets and platelet derived microvesicles (PMVs) emerged recently to be promising biomarkers. There is no universal procedure to carry out the proteomic analysis on microvesicles. In this study we proposed a nano-liquid chromatography (nano-LC) technique coupled off-line with a spectrometric measurement MALDI-TOF-MS/MS as a throughput and time-saving procedure. In this study we developed a simplified method to evaluate the protein composition of platelet organelles and PMVs. Platelet-rich plasma (PRP) was collected from healthy donors...
November 16, 2016: Clinical Biochemistry
https://www.readbyqxmd.com/read/27862691/evaluation-of-the-use-of-global-haemostasis-assays-to-monitor-treatment-in-factor-xi-deficiency
#20
G N Pike, A M Cumming, J Thachil, C R M Hay, J Burthem, P H B Bolton-Maggs
INTRODUCTION: Previous guidelines recommend that FXI:C levels should be used to monitor FXI replacement in factor XI (FXI) deficiency. However, FXI:C levels do not correlate with bleeding tendency in this disorder and may not be the optimal test by which to monitor and determine further treatment in the postoperative period. AIM: To assess whether the thrombin generation assay (TGA) and rotational thromboelastometry can be used to monitor FXI replacement peri-operatively in FXI deficiency and to determine if changes in FXI:C levels correlate with changes in thrombin generation and clot formation parameters following treatment with solvent-detergent fresh frozen plasma (SD-FFP)...
November 8, 2016: Haemophilia: the Official Journal of the World Federation of Hemophilia
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