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https://www.readbyqxmd.com/read/27913542/new-therapies-for-hemophilia
#1
Steven W Pipe
Individuals with severe hemophilia have benefitted from 5 decades of advances that have led to widespread availability of safe and efficacious factors VIII and IX, a multidisciplinary integrated care model through a network of specialized hemophilia treatment centers, and aggressive introduction of prophylactic replacement therapy to prevent bleeding and preserve joint health. Yet, there are remaining challenges and treatment gaps which have prevented complete abrogation of all joint bleeding, and progressive joint deterioration may continue in some affected individuals over the course of a lifetime...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27912791/possible-failure-of-novel-direct-acting-oral-anticoagulants-in-management-of-pulmonary-embolism-a-case-report
#2
James Rankin, Menachem Nagar, Jonathan Crosby, Nojan Toomari, Richard Pietras, Uri M Ben-Zur
BACKGROUND: The relative effectiveness of vitamin K antagonists compared with novel oral anticoagulants in treating pulmonary embolism remains unclear. Recent trials comparing the efficacy of vitamin K antagonists with factor Xa inhibitors for the treatment of pulmonary emboli have been non-inferiority studies based primarily on risk reduction (such as bleeding events), rather than resolution of specific diseases such as pulmonary embolism. Consequently, there is a lack of evidence indicating which of these agents are more effective...
December 3, 2016: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/27908894/contraction-of-blood-clots-is-impaired-in-acute-ischemic-stroke
#3
Valerie Tutwiler, Alina D Peshkova, Izabella A Andrianova, Dina R Khasanova, John W Weisel, Rustem I Litvinov
OBJECTIVE: Obstructive thrombi or thrombotic emboli are the pathogenic basis of ischemic stroke. In vitro blood clots and in vivo thrombi can undergo platelet-driven contraction (retraction), resulting in volume shrinkage. Clot contraction can potentially reduce vessel occlusion and improve blood flow past emboli or thrombi. The aim of this work was to examine a potential pathogenic role of clot contraction in ischemic stroke. APPROACH AND RESULTS: We used a novel automated method that enabled us to quantify time of initiation and extent and rate of clot contraction in vitro...
December 1, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27906868/individual-clotting-factor-contributions-to-mortality-following-trauma
#4
Ryan C Kunitake, Benjamin M Howard, Lucy Z Kornblith, Sabrinah A Christie, Amanda S Conroy, Mitchell J Cohen, Rachael A Callcut
BACKGROUND: Acute traumatic coagulopathy (ATC) afflicts 20-30% of trauma patients, but the extensive collinearity of the coagulation cascade complicates attempts to clarify global clotting factor dysfunction. This study aims to characterize phenotypes of clotting factor dysfunction and their contributions to mortality after major trauma. METHODS: This prospective cohort study examines all adult trauma patients of the highest activation level presenting to San Francisco General Hospital between 2/2005 and 2/2015...
November 30, 2016: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/27906086/massive-adrenal-vein-aneurysm-mimicking-an-adrenal-tumor-in-a-patient-with-hemophilia-a-a-case-report-and-review-of-the-literature
#5
Richard Sleightholm, Steven Wahlmeier, Jeffrey S Carson, Andjela Drincic, Audrey Lazenby, Jason M Foster
BACKGROUND: Visceral venous aneurysms are exceedingly rare, and until now, there have been no reports of this phenomenon in the adrenal vasculature. This report details the first adrenal venous aneurysm reported in the literature. The aneurysm presented as an 18-cm mass that was initially suspected to be a hematoma or tumor on the basis of the complex medical history of the patient, which included hemophilia A and testicular cancer. After surgical excision, pathologic examination confirmed this mass to be a 15...
December 1, 2016: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/27902939/factor-xiii-deficiency-enhances-thrombin-generation-due-to-impaired-fibrin-polymerization-an-effect-corrected-by-factor-xiii-replacement
#6
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
#7
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
#8
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/27899173/procoagulant-role-of-microparticles-in-routine-storage-of-packed-red-blood-cells-potential-risk-for-prothrombotic-post-transfusion-complications
#9
Htet Htet Aung, John-Paul Tung, Melinda M Dean, Robert L Flower, Natalie M Pecheniuk
During routine storage, packed red blood cells (PRBC) undergo biochemical and morphological changes including loss of red blood cell (RBC) membrane asymmetry and release of microparticles (MPs) bearing phosphatidylserine (PS), a procoagulant phospholipid. This study investigated the association between PRBC storage duration, MP profile and procoagulant activity. Leukodepleted PRBC-supernatant (PRBC-SN; n=13) was prepared at weekly intervals throughout storage. Phospholipid-dependent procoagulant activity, assessed using a factor X-activated clotting time (XACT) assay, decreased throughout storage (p<0...
November 26, 2016: Pathology
https://www.readbyqxmd.com/read/27895055/role-of-agents-for-reversing-the-effects-of-target-specific-oral-anticoagulants
#10
REVIEW
Tanya R Riley, Mary L Gauthier-Lewis, Chelsea K Sanchez, Janine S Douglas
PURPOSE: The available clinical data on target-specific oral anticoagulant (TSOAC) reversal agents that are currently in development or have been approved by the Food and Drug Administration (FDA) are reviewed. SUMMARY: The development of TSOACs such as dabigatran, rivaroxaban, edoxaban, and apixaban has presented benefits and new challenges. One of the main challenges associated with the use of TSOACs is the lack of suitable agent-specific reversal agents. Several treatment options for the management of life-threatening bleeding events associated with TSOAC use, such as fresh frozen plasma, prothrombin complex concentrates, and recombinant coagulation factor VIIa, have been used, with inconsistent results...
November 28, 2016: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/27894935/brief-report-stage-specific-differences-in-secretory-profile-of-mesenchymal-stromal-cells-mscs-subjected-to-early-vs-late-stage-oa-synovial-fluid
#11
Alejandro Gómez-Aristizábal, Anirudh Sharma, Mohsen A Bakooshli, Mohit Kapoor, Penney M Gilbert, Sowmya Viswanathan, Rajiv Gandhi
OBJECTIVE: Although, mesenchymal stromal cells (MSCs) are being clinically investigated for their use in osteoarthritis (OA), it is unclear whether their postulated therapeutic properties are equally effective in the early- and late-stages of OA. In this study we investigated MSC cytokine secretion post-exposure to synovial fluid (SF), obtained from early-vs. late-stage knee OA patients to justify a potential patient stratification strategy to maximize MSC-mediated treatment effects. METHOD: Subjects were recruited and categorized into early- [Kellgren-Lawrence (KL) grade I/II, n = 12] and late-stage (KL-III/IV, n = 12) knee OA groups...
November 25, 2016: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/27894217/diagnosis-clinical-manifestations-and-management-of-rare-bleeding-disorders-in-iran
#12
Akbar Dorgalaleh, Sayed Ezatolla Rafiee Alavi, Shadi Tabibian, Shahrzad Soori, Es'hagh Moradi, Taregh Bamedi, Mansour Asadi, Masumeh Jalalvand, Morteza Shamsizadeh
BACKGROUND: Rare bleeding disorders (RBDs) are heterogeneous disorders, mostly inherited in an autosomal recessive pattern. Iran is a Mideast country with a high rate of consanguinity that has a high rate of RBDs. OBJECTIVE: In this study, we present prevalence and clinical presentation as well as management and genetic defects of Iranian patients with RBDs. METHODS: For this study, all relevant publications were searched in Medlin until 2015...
November 28, 2016: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/27891624/quarantine-versus-pathogen-reduced-plasma-coagulation-factor-content-and-rotational-thromboelastometry-coagulation
#13
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/27890816/pathophysiology-of-hemophilic-arthropathy-and-potential-targets-for-therapy
#14
REVIEW
Astrid E Pulles, Simon C Mastbergen, Roger E G Schutgens, Floris P J G Lafeber, Lize F D van Vulpen
Hemophilia is a congenital clotting factor deficiency characterized by spontaneous and trauma-related bleeding. Spontaneous bleeding shows a predilection for joints, and repeated hemarthroses lead to a disabling condition called hemophilic arthropathy. Treatment of this condition consists of preventing joint bleeding on the one hand and orthopedic surgery as a last resort on the other. Up till now, there is no disease modifying therapy available to fill the gap between these extremes. This review provides an overview of the pathogenesis of hemophilic arthropathy in order to identify potential targets for therapy...
November 24, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27890467/use-of-hyperbaric-oxygen-therapy-and-pegylated-carboxyhemoglobin-bovine-in-a-jehovah-s-witness-with-life-threatening-anemia-following-postpartum-hemorrhage
#15
K Thenuwara, J Thomas, M Ibsen, U Ituk, K Choi, E Nickel, M J Goodheart
We present a case of a Jehovah's Witness patient who refused blood products, with the exception of albumin and clotting factors, and underwent cesarean section under spinal anesthesia complicated by postpartum hemorrhage. She was fluid resuscitated and treated with multiple uterotonics and internal iliac artery embolization. Because of agitation she required emergency tracheal intubation. Her hemoglobin concentration dropped from a preoperative value of 12mg/dL to 3mg/dL on postoperative day one. She was acidotic, requiring vasopressors for hemodynamic stability and remained ventilated and sedated...
October 24, 2016: International Journal of Obstetric Anesthesia
https://www.readbyqxmd.com/read/27888608/efficacy-and-safety-of-combined-intraventricular-fibrinolysis-with-lumbar-drainage-for-prevention-of-permanent-shunt-dependency-after-intracerebral-hemorrhage-with-severe-ventricular-involvement-a-randomized-trial-and-individual-patient-data-meta-analysis
#16
Dimitre Staykov, Joji B Kuramatsu, Jürgen Bardutzky, Bastian Volbers, Stefan T Gerner, Stephan P Kloska, Arnd Doerfler, Stefan Schwab, Hagen B Huttner
Objective Intraventricular hemorrhage (IVH) is a negative prognostic factor in intracerebral hemorrhage (ICH) and is associated with permanent shunt dependency in a substantial proportion of patients after ICH. IVH treatment by intraventricular fibrinolysis (IVF) was recently linked to reduced mortality rates in the CLEAR III study and IVF represents a safe and effective strategy to hasten clot resolution that may reduce shunt rates. Additionally, promising results from observational studies reported reductions in shunt dependency for a combined treatment approach of IVF plus lumbar drains (LD)...
November 26, 2016: Annals of Neurology
https://www.readbyqxmd.com/read/27886531/coagulation-and-sepsis
#17
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/27881835/leptospirosis-associated-severe-pulmonary-hemorrhagic-syndrome-with-lower-back-pain-as-an-initial-symptom
#18
Mads Madsen Søndergaard, Amela Tursunovic, Peter Thye-Rønn, Jacob Christian Bang, Inger Marie Jensen Hansen
BACKGROUND Leptospirosis is a zoonosis transmitted through urine of infected animals. Symptoms range from mild influenza-like symptoms to severe pulmonary hemorrhagic syndrome (SPHS); the latter are often fatal. The serogroup distribution in Denmark has changed from 1988 to 2012, with Icterohaemorrhagiae and Sejroe now being predominant. CASE REPORT A 45-year-old Danish woman living in an area endemic for Hanta virus, without prior medical history, was admitted because of lower back pain radiating to the left hip, fever, headache, nausea, and malaise...
November 24, 2016: American Journal of Case Reports
https://www.readbyqxmd.com/read/27876598/antithrombotic-activity-of-batroxase-a-metalloprotease-from-bothrops-atrox-venom-in-a-model-of-venous-thrombosis
#19
Anna L Jacob-Ferreira, Danilo L Menaldo, Marco A Sartim, Thalita B Riul, Marcelo Dias-Baruffi, Suely V Sampaio
BACKGROUND: Snake venoms are great sources of bioactive molecules, which may be used as models for new drugs. Toxins that interfere in hemostasis have received considerable attention over the years. OBJECTIVES: This study aimed at the evaluation of the antithrombotic activity of Batroxase, a P-I metalloprotease from Bothrops atrox venom, in an animal model of venous thrombosis. METHODS: The antithrombotic activity of Batroxase was tested in vivo in a model based on two factors of the Virchow's Triad: blood flow alterations (partial stenosis of the inferior vena cava), and vessel wall injury (10% ferric chloride for 5min), in comparison with sodium heparin (positive control) and saline (negative control)...
November 19, 2016: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/27874025/beyond-antibodies-development-of-a-novel-protein-scaffold-based-on-human-chaperonin-10
#20
Abdulkarim M Alsultan, David Y Chin, Christopher B Howard, Christopher J de Bakker, Martina L Jones, Stephen M Mahler
Human Chaperonin 10 (hCpn10) was utilised as a novel scaffold for presenting peptides of therapeutic and diagnostic significance. Molecular dynamic simulations and protein sizing analyses identified a peptide linker (P1) optimal for the formation of the quarternary hCpn10 heptamer structure. hCpn10 scaffold displaying peptides targeting Factor VIIa (CE76-P1) and CD44 (CP7) were expressed in E. coli. Functional studies of CE76-P1 indicated nanomolar affinity for Factor VIIa (3 nM) similar to the E-76 peptide (6 nM), with undetectable binding to Factor X...
November 22, 2016: Scientific Reports
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