Read by QxMD icon Read

factor XII

Joanne L Mitchell, Ausra S Lionikiene, Georgi Georgiev, Anja Klemmer, Chelsea Brain, Paul Y Kim, Nicola J Mutch
Activated factor XII (FXIIa) has plasminogen activator capacity but its relative contribution to fibrinolysis is considered marginal compared to urokinase and tissue plasminogen activator. Polyphosphate (polyP) is released from activated platelets and mediates FXII activation. Here we investigate the contribution of polyP to the plasminogen activator function of αFXIIa. We show that both polyP70, of the chain length found in platelets (60-100-mer) and platelet-derived polyP, significantly augment the plasminogen activation capacity of αFXIIa...
September 30, 2016: Blood
Benilde Cosmi
Anticoagulants such as heparins and vitamin K antagonists (VKA) are effective for thrombosis prevention and treatment, but are associated with the risk of bleeding and other limitations, spurring the search for improved drugs. Areas covered: to evaluate the newer anticoagulants, focusing on those tested in phase III clinical trials such as direct oral anticoagulants (DOACs), antisense oligonucleotides (ASO) and warfarin analogues. DOACs such as dabigatran, rivaroxaban, apixaban and edoxaban are licensed for stroke prevention in atrial fibrillation and treatment of venous thromboembolism, dabigatran, rivaroxaban and apixaban for postoperative thromboprophylaxis in patients undergoing elective hip or knee arthroplasty and rivaroxaban for secondary prevention of acute coronary syndromes...
October 12, 2016: Expert Opinion on Pharmacotherapy
Allison P Wheeler, David Gailani
Plasma coagulation in the activated partial thromboplastin time assay is initiated by sequential activation of coagulation factors XII, XI, and IX. While this series of proteolytic reactions is not an accurate model for hemostasis in vivo, there is mounting evidence that factor XI and factor XII contribute to thrombosis, and that inhibiting them can produce an antithrombotic effect with a small effect on hemostasis. This article discusses the contributions of components of the intrinsic pathway to thrombosis in animal models and humans, and results of early clinical trials of drugs targeting factors IX, XI, and XII...
October 2016: Hematology/oncology Clinics of North America
Marie V Lukassen, Carsten Scavenius, Ida B Thøgersen, Jan J Enghild
Transforming growth factor β-induced protein (TGFBIp) is an extracellular matrix protein composed of an NH2-terminal cysteine-rich domain (CRD) annotated as an emilin (EMI) domain and four fasciclin-1 (FAS1-1-FAS1-4) domains. Mutations in the gene cause corneal dystrophies, a group of debilitating protein misfolding diseases that lead to severe visual impairment. Previous studies have shown that TGFBIp in the cornea is cross-linked to type XII collagen through a reducible bond. TGFBIp contains 11 cysteine residues and is thus able to form five intramolecule disulfide bonds, leaving a single cysteine residue available for the collagen cross-link...
October 4, 2016: Biochemistry
Linda Labberton, Ellinor Kenne, Andy T Long, Katrin F Nickel, Antonio Di Gennaro, Rachel A Rigg, James S Hernandez, Lynn Butler, Coen Maas, Evi X Stavrou, Thomas Renné
Polyphosphate is an inorganic procoagulant polymer. Here we develop specific inhibitors of polyphosphate and show that this strategy confers thromboprotection in a factor XII-dependent manner. Recombinant Escherichia coli exopolyphosphatase (PPX) specifically degrades polyphosphate, while a PPX variant lacking domains 1 and 2 (PPX_Δ12) binds to the polymer without degrading it. Both PPX and PPX_Δ12 interfere with polyphosphate- but not tissue factor- or nucleic acid-driven thrombin formation. Targeting polyphosphate abolishes procoagulant platelet activity in a factor XII-dependent manner, reduces fibrin accumulation and impedes thrombus formation in blood under flow...
2016: Nature Communications
Qasam M Ghulam, Kim K Bredahl, Jørgen B Gram, Lars Lönn, Jens P Goetze, Henrik H Sillesen, Jonas P Eiberg
OBJECTIVES: Disruption of the endothelial lining may be one of the events linking intraluminal thrombus and abdominal aortic aneurysm growth. In the present study, we examined whether von Willebrand factor activity in plasma, contact proteins of blood coagulation, and inflammatory biomarkers may be associated with intraluminal thrombus volume in search of a biochemical marker of endothelial damage and thrombus size. DESIGN: Prospective study, correlating potential endothelial biomarkers and intraluminal thrombus volume acquired by computed tomography angiography...
August 2016: Vascular and Endovascular Surgery
Chunhui Yang, Guohui Bian, Hong Yang, Xinmin Zhang, Limin Chen, Jingxing Wang
High hydrostatic pressure has been used to inactivate pathogens in foods for decades. There is a great potential to adapt this technology to inactivate pathogens in plasma and derivatives. To better evaluate the potential of this method, pathogen inoculated plasma samples were pressurized under different pressure application modes and temperatures. The inactivation efficacy of pathogens and activities of plasma proteins were monitored after treatment. The CFUs of E.coli was examined as the indicator of the inactivation efficiency...
2016: PloS One
Ashley Barratclough, Ruth Francis Floyd, Bobbi Conner, Roger Reep, Ray Ball, Nicole Stacy
Hemostatic disorders presumptively play an important role in the pathophysiology of several important disease conditions in the Florida manatee ( Trichechus manatus latirostris). Prior to pursuing such clinical implications, it is essential to establish normal hemostatic profiles in clinically healthy animals. During annual health assessments of free-living manatees organized by the US Geological Survey, blood samples were collected from 12 healthy animals from the Atlantic coast and 28 from the Gulf of Mexico coast of Florida, with body lengths of 210-324 cm...
October 2016: Journal of Wildlife Diseases
Giuseppe Tagariello, Paolo Radossi, Roberta Salviato, Milena Zardo, Lucia De Valentin, Marco Basso, Giancarlo Castaman
BACKGROUND: Coagulation screening prior to surgery is performed routinely worldwide to identify patients at risk of bleeding during the procedure. Evidence from medical and surgical literature suggests that the activated partial thromboplastin time (aPTT) alone is suitable for predicting individual bleeding risk during surgery and it is current practice in our hospital to measure this parameter. MATERIALS AND METHODS: We retrospectively reviewed aPTT ratio results in 8,069 consecutive adult subjects undergoing elective surgery from January 1 to December 31, 2014 to confirm the validity of this approach...
July 22, 2016: Blood Transfusion, Trasfusione del Sangue
M Cicardi, C Suffritti, F Perego, S Caccia
Angioedema is defined as local, noninflammatory, self-limiting edema that is circumscribed owing to increased leakage of plasma from the capillaries located in the deep layers of the skin and the mucosae. Two mediators, histamine and bradykinin, account for most cases of angioedema. Angioedema can occur with wheals as a manifestation of urticaria, and this form is frequently allergic. In the present review, we discuss nonallergic angioedema without wheals, which can be divided into 3 acquired and 4 hereditary forms...
2016: Journal of Investigational Allergology & Clinical Immunology
Alexander J Donovan, Joseph Kalkowski, Magdalena Szymusiak, Canhui Wang, Stephanie A Smith, Robert F Klie, James H Morrissey, Ying Liu
Granular platelet-sized polyphosphate nanoparticles (polyP NPs) were encapsulated in sterically stabilized liposomes, forming a potential, targeted procoagulant nanotherapy resembling human platelet dense granules in both structure and functionality. Dynamic light scattering (DLS) measurements reveal that artificial dense granules (ADGs) are colloidally stable and that the granular polyP NPs are encapsulated at high efficiencies. High-resolution scanning transmission electron microscopy (HR-STEM) indicates that the ADGs are monodisperse particles with a 150 nm diameter dense core consisting of P, Ca, and O surrounded by a corrugated 25 nm thick shell containing P, C, and O...
August 8, 2016: Biomacromolecules
Alvin H Schmaier
PURPOSE OF REVIEW: This report examines the mechanism(s) by which each protein of the contact activation system - factor XII (FXII), high-molecular-weight kininogen, and prekallikrein - influences thrombosis risk. RECENT FINDINGS: FXII generates thrombin through contact activation via interaction with artificial surfaces as on medical instruments such as indwelling catheters, mechanical valves, stents, and ventricular assist devices. Inhibition of FXIIa-mediated contact activation prevents thrombosis under contact activation circumstances without affecting hemostasis...
September 2016: Current Opinion in Hematology
Brian C Cooley
Whereas the extrinsic pathway of coagulation seals off bleeding at the cut tissue edges, it is proposed that the intrinsic pathway exploits the dirt from the skin surface to generate an outer coagulum of the oozing blood. Activated Factor XII (FXIIa) in this outer cap generates Factor XIa, which triggers clotting, and kallikrein that feeds back to form more FXIIa to promote the process. This dirty-wound hypothesis of coagulation function by the intrinsic pathway is supported by the use of dirt-based compounds in activated partial thromboplastin time assays as well as the evolutionary record where marine life that do not have skin-adherent dirt lack Factor XII, including marine mammals that have returned to sea life...
September 2016: Thrombosis Research
D Biltoft, J J Sidelmann, L F Olsen, Y Palarasah, J Gram
OBJECTIVES: The physiological role of the contact system remains inconclusive. No obvious clinical complications have been observed for factor XII (FXII), prekallikrein (PK), or high molecular weight kininogen deficiencies even though the contact system in vitro is associated with coagulation, fibrinolysis, and inflammation. A global generation assay measuring the initial phase of the contact system could be a valuable tool for studies of its physiological role. DESIGN AND METHODS: We investigated whether such a method could be developed using the principle of the Calibrated Automated Thrombin generation method as a template...
June 29, 2016: Clinical Biochemistry
S de Maat, C Maas
Factor XII is a mysterious plasma protein without a clear physiologic function. It was identified as a clotting factor, but has no clear role in hemostasis. However, FXII also contributes to the production of bradykinin, a short-lived inflammatory peptide. A growing body of mechanistic research from animal models indicates that FXII contributes to thrombotic disease by triggering excessive coagulation. FXII is evolutionarily conserved, suggesting that this molecule does have a physiologic function. This leads to intriguing questions: What does FXII really do? Is it even a real clotting factor at all? Before the groundbreaking discovery of a role for FXII in thrombotic disease, many studies investigated the biochemical properties of FXII and its activators...
August 2016: Journal of Thrombosis and Haemostasis: JTH
Allen P Kaplan, Kusumam Joseph
Plasma of patients with types I and II hereditary angioedema is unstable if incubated in a plastic (i.e., inert) vessel at 37 °C manifested by progressively increasing formation of bradykinin. There is also a persistent low level of C4 in 95 % of patients even when they are symptomatic. These phenomena are due to the properties of the C1r subcomponent of C1, factor XII, and the bimolecular complex of prekallikrein with high molecular weight kininogen (HK). Purified C1r auto-activates in physiologic buffers, activates C1s, which in turn depletes C4...
October 2016: Clinical Reviews in Allergy & Immunology
A Deroux, I Boccon-Gibod, O Fain, P Pralong, Y Ollivier, A Pagnier, K Djenouhat, A Du-Thanh, A Gompel, C Faisant, D Launay, L Bouillet
Hereditary angioedema (HAE) is a rare disease associated with either a quantitative or qualitative deficiency in C1-inhibitor (C1-INH) or normal C1-INH. HAE with normal C1-INH is associated in 20% of cases with mutations in the gene for factor XII (FXII) or FXII-HAE. A recent review described 41 families, including 14 German and 15 Spanish families. We have constructed a register of French patients and their characteristics. A national survey was launched through the French National Center of Reference for Angioedema (CREAK) to study the clinical, biological and therapeutic characteristics of patients with HAE linked to a mutation of FXII gene...
September 2016: Clinical and Experimental Immunology
Lu Yang, Yun Li, Arup Bhattacharya, Yuesheng Zhang
Coagulation factors are essential for hemostasis. Here, we show that these factors also team up to degrade plasma proteins that are unrelated to hemostasis. Prolidase, SRC and amyloid β1-42 (Aβ1-42) are used as probes. Each probe, upon entering the blood circulation, binds and activates factor XII (FXII), triggering the intrinsic and common coagulation cascades, which in turn activate factor VII, a component of the extrinsic coagulation cascade. Activated factor VII (FVIIa) rapidly degrades the circulating probes...
February 7, 2016: Oncotarget
Cristina Puy, Rachel A Rigg, Owen J T McCarty
Coagulation factor (F)XI has been described as a component of the early phase of the contact pathway of blood coagulation, acting downstream of factor XII. However, patients deficient in upstream members of the contact pathway, including FXII and prekallikrein, do not exhibit bleeding complications, while FXI-deficient patients sometimes experience mild bleeding, suggesting FXI plays a role in hemostasis independent of the contact pathway. Further complicating the picture, bleeding risk in FXI-deficient patients is difficult to predict because bleeding symptoms have not been found to correlate with FXI antigen levels or activity...
May 2016: Thrombosis Research
Daria Zamolodchikov, Sidney Strickland
Alzheimer's disease (AD) is often characterized by vascular pathology, a procoagulant state, and chronic inflammation. The mechanisms behind these abnormalities in AD are not clear. Here, we review evidence for the role of the AD-associated peptide Aβ in promoting inflammation and thrombosis in AD via its interaction with the circulating proteins factor XII and fibrinogen.
May 2016: Thrombosis Research
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"