A5035706645- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Blood Coagulation and Thrombosis Mechanisms
- Mast cells and histamine
- Urticaria and Related Conditions
- Vitamin K Research Studies
- Autoimmune Bullous Skin Diseases
- Hemophilia Treatment and Research
- Chronic Myeloid Leukemia Treatments
- Hemostasis and retained surgical items
- Food Allergy and Anaphylaxis Research
- Enzyme function and inhibition
- Complement system in diseases
- Atrial Fibrillation Management and Outcomes
- Venous Thromboembolism Diagnosis and Management
- Antiplatelet Therapy and Cardiovascular Diseases
Karolinska University Hospital
2013-2016
Karolinska Institutet
2011-2016
University Medical Center Hamburg-Eppendorf
2015-2016
Universität Hamburg
2015-2016
AstraZeneca (Sweden)
2014
Blocking the enzyme that initiates intrinsic coagulation pathway protects against thrombosis in bypass systems and does not cause excess bleeding vivo.
Hereditary angioedema type III (HAEIII) is a rare inherited swelling disorder that associated with point mutations in the gene encoding plasma protease factor XII (FXII). Here, we demonstrate HAEIII-associated mutant FXII, derived either from HAEIII patients or recombinantly produced, defective mucin-type Thr309-linked glycosylation. Loss of glycosylation led to increased contact-mediated autoactivation zymogen resulting excessive activation bradykinin-forming kallikrein-kinin pathway. In...
Human plasma-derived C1-esterase inhibitor (C1-INH) is an efficacious and safe treatment for hereditary angioedema. However, thrombotic events in subjects treated with C1-INH at recommended or off-label, high doses have been reported. In this study, we addressed the potential prothrombotic risk of using a non-clinical rabbit model. Following intravenous infusion to rabbits up 800 IU/kg, exposure pharmacodynamic efficacy were confirmed by activity measurements C1-esterase, coagulation factors...
Abstract Contact to polyanions induces autoactivation of the serine protease factor XII that triggers kallikrei-kinin system. Recent studies indicate polysaccharide-induced has a role in allergy-related vascular leakage, and angioedema. Here, we characterize vivo effects synthetic polysaccharide dextran sulfate human plasma rodent models. Minute amounts high-molecular-weight sulfate-initiated XII-autoactivation triggered formation inflammatory mediator bradykinin via kallikrein-mediated...
In the activated partial thromboplastin time (APTT) assay, a variety of nonphysiological reagents is used to induce contact activation. The sensitivity APTT response for different thrombin inhibitors has previously been found be dependent on reagent. Recently, infusion prothrombin (FII) in in-vivo coagulopathy models and its effect analyzed assays. Therefore, we investigated whether FII plasma concentration might affect using commercial reagents, applying both turbidimetry viscometry. We...
When investigating coagulation assays to measure the effect of infused prothrombin (FII) in vivo coagulopathy models, we found that addition FII, plasma-derived human FII (pd-hFII) or recombinant (r-hFII), normal plasma resulted a concentration-dependent increase time (PT) initiated with Innovin(®) .The on PT by either pd-hFII r-hFII, using different commercial reagents, was studied both turbidimetry and viscometry.Addition increased when : 20% doubling concentration. The prolongation became...