Thrombozytenaggregationshemmer

2003 ◽  
Vol 23 (04) ◽  
pp. 181-185 ◽  
Author(s):  
H. Patscheke
Keyword(s):  
Point Of Care ◽  
Von Willebrand

ZusammenfassungUnabhängig von ihrem Wirkungsmechanismus greifen Antikoagulanzien stets unmittelbar in die Bildung und Wirkung von Thrombin und damit die Endstrecke der Gerinnung ein. Von den Aggregationshemmern hemmen nur die GPIIb/IIIa-Antagonisten die gemeinsame Endstrecke der Plättchenaggregation, indem sie die Bildung von Fibrinogen/von-Willebrand-Faktor-vermittelten Plättchen-Plättchen-Brücken hemmen.Azetylsalizylsäure (ASS), NSARs, Clopidogrel oder Ticlopidin begrenzen die Plättchenaktivierung dagegen, indem sie die Bildung bzw. Wirkung der sekundären Plättchenagonisten Thromboxan A2 bzw. ADP ausschalten, aber z. B. die durch Thrombin direkt induzierbare Plättchenaggregation nicht. Deshalb rufen ASS, Clopidogrel oder Ticlopidin allein kein wesentliches Blutungsrisiko hevor, wenn nicht weitere, die Hämostase beeinträchtigende Faktoren (z.B. ausgeprägte Thrombozytopenie, Antikoagulation) vorliegen. Deshalb entfällt für diese Hemmstoffe auch die Notwendigkeit der Therapiekontrolle. Beim therapeutischen Einsatz von ASS als Aggregationshemmer ist vielmehr die Dosierung darauf abzustellen, eine vollständige Blockade (mind. 90%) der Thromboxanbiosynthese in den Plättchen zu erreichen, um überhaupt einen therapeutischen bzw. prophylaktischen Effekt zu erzielen.Von den GPIIb/IIIa-Antagonisten sind nur die parenteral eingesetzten (Abciximab, Eptifibatid, Tirofiban) zugelassen. Orale GPIIb/IIIa-Antagonisten zeigten bisher in klinischen Studien ein erhöhtes Blutungsrisiko bei nicht ausreichendem therapeutischen Nutzen. Die meisten GPIIb/IIIa-Antagonisten verursachen eine leichte Thrombozytopenie, als deren Auslöser die Inhibitor-Rezeptor-Wechselwirkung bzw. immunologische Mechanismen diskutiert werden. Für das spezifische Monitoring dieser potenten Aggregationshemmer ist ein »Point-of-Care«-Testsystem verfügbar. Für die Einschätzung des Blutungsrisikos müssen jedoch stets alle, die Hämostase beeinflussende Faktoren berücksichtigt werden. Das gilt insbesondere, wenn neben GPIIb/IIIa-Antagonisten Heparin u.a. Wirkstoffe eingesetzt werden.

scholarly journals A polymer-based systemic hemostatic agent

2020 ◽  
Vol 6 (31) ◽  
pp. eaba0588 ◽  
Author(s):  
Yongsheng Gao ◽  
Apoorva Sarode ◽  
Nikolaos Kokoroskos ◽  
Anvay Ukidve ◽  
Zongmin Zhao ◽  
...  
Keyword(s):  
Point Of Care ◽  
Vena Cava ◽  
In Vivo Studies ◽  
Hemostatic Agent ◽  
Binding Peptide ◽  
Military Populations ◽  
Acid Conjugate ◽  
Von Willebrand

Uncontrolled noncompressible hemorrhage is a major cause of mortality following traumatic injuries in civilian and military populations. An injectable hemostat for point-of-care treatment of noncompressible hemorrhage represents an urgent medical need. Here, we describe an injectable hemostatic agent via polymer peptide interfusion (HAPPI), a hyaluronic acid conjugate with a collagen-binding peptide and a von Willebrand factor–binding peptide. HAPPI exhibited selective binding to activated platelets and promoted their accumulation at the wound site in vitro. In vivo studies in mouse tail vein laceration model demonstrated a reduction of >97% in both bleeding time and blood loss. A 284% improvement in the survival time was observed in the rat inferior vena cava traumatic model. Lyophilized HAPPI could be stably stored at room temperature for several months and reconstituted during therapeutic intervention. HAPPI provides a potentially clinically translatable intravenous hemostat.

scholarly journals Pulmonary Embolism in COVID-19 Patients: Facts and Figures

2021 ◽  
Author(s):  
Nissar Shaikh ◽  
Narges Quyyum ◽  
Arshad Chanda ◽  
Muhammad Zubair ◽  
Muhsen Shaheen ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Point Of Care ◽  
Pulmonary Arteries ◽  
Pulmonary Angiography ◽  
Standard Test ◽  
Plasma Therapy ◽  
Therapeutic Anticoagulation ◽  
Increased Risk ◽  
Lower Mobility ◽  
Von Willebrand

COVID-19 infection affects many systems in the body including the coagulation mechanisms. Imbalance between pro-coagulant and anticoagulant activities causes a roughly nine times higher risk for pulmonary embolism (PE) in COVID-19 patients. The reported incidence of PE in COVID-19 patients ranges from 3 to 26%. There is an increased risk of PE in hospitalized patients with lower mobility and patients requiring intensive care therapy. Obesity, atrial fibrillation, raised pro-inflammatory markers, and convalescent plasma therapy increases the risk of PE in COVID-19 patients. Endothelial injury in COVID-19 patients causes loss of vasodilatory, anti-adhesion and fibrinolytic properties. Viral penetration and load leads to the release of cytokines and von Willebrand factor, which induces thrombosis in small and medium vessels. D-dimers elevation gives strong suspicion of PE in COVID-19 patients, and normal D-dimer levels effectively rule it out. Point of care echocardiogram may show right heart dilatation, thrombus in heart or pulmonary arteries. DVT increases the risk of developing PE. The gold standard test for the diagnosis of PE is CTPA (computerized tomographic pulmonary angiography) which also gives alternative diagnosis in the absence of PE. Therapeutic anticoagulation is the corner stone in the management of PE and commonly used anticoagulants are LMWH (low molecular weight heparin) and UFH (unfractionated heparin). Mortality in COVID-19 patients with PE is up to 43% compared to COVID patients without PE being around 3%.

scholarly journals Covid-19: The Rollercoaster of Fibrin(Ogen), D-Dimer, Von Willebrand Factor, P-Selectin and Their Interactions with Endothelial Cells, Platelets and Erythrocytes

2020 ◽  
Vol 21 (14) ◽  
pp. 5168 ◽  
Author(s):  
Corlia Grobler ◽  
Siphosethu C. Maphumulo ◽  
L. Mireille Grobbelaar ◽  
Jhade C. Bredenkamp ◽  
Gert J. Laubscher ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Von Willebrand Factor ◽  
Poor Prognosis ◽  
Point Of Care ◽  
Signalling Pathways ◽  
Platelet Dysfunction ◽  
Multiple Risk Factors ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
D Dimer

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), also known as coronavirus disease 2019 (COVID-19)-induced infection, is strongly associated with various coagulopathies that may result in either bleeding and thrombocytopenia or hypercoagulation and thrombosis. Thrombotic and bleeding or thrombotic pathologies are significant accompaniments to acute respiratory syndrome and lung complications in COVID-19. Thrombotic events and bleeding often occur in subjects with weak constitutions, multiple risk factors and comorbidities. Of particular interest are the various circulating inflammatory coagulation biomarkers involved directly in clotting, with specific focus on fibrin(ogen), D-dimer, P-selectin and von Willebrand Factor (VWF). Central to the activity of these biomarkers are their receptors and signalling pathways on endothelial cells, platelets and erythrocytes. In this review, we discuss vascular implications of COVID-19 and relate this to circulating biomarker, endothelial, erythrocyte and platelet dysfunction. During the progression of the disease, these markers may either be within healthy levels, upregulated or eventually depleted. Most significant is that patients need to be treated early in the disease progression, when high levels of VWF, P-selectin and fibrinogen are present, with normal or slightly increased levels of D-dimer (however, D-dimer levels will rapidly increase as the disease progresses). Progression to VWF and fibrinogen depletion with high D-dimer levels and even higher P-selectin levels, followed by the cytokine storm, will be indicative of a poor prognosis. We conclude by looking at point-of-care devices and methodologies in COVID-19 management and suggest that a personalized medicine approach should be considered in the treatment of patients.

»Point-of-care Testing« Vollblutmethoden in der Hämostasediagnostik

2000 ◽  
Vol 20 (01) ◽  
pp. 13-16
Author(s):  
W. A. Wuillemin
Keyword(s):  
Point Of Care ◽  
Point Of Care Testing ◽  
Point Of Care Tests ◽  
Von Willebrand ◽  
D Dimer

ZusammenfassungPoint-of-care-Tests (POCT) mit Vollblut gibt es für verschiedene Analysen im Bereich der Hämostase. Am häufigsten wird die Thromboplastinzeit mit Kapillarblut durchgeführt. Diese POCT-Analyse ist zuverlässig und wird u. a. bei der Patientenselbstkontrolle der oralen Antikoagulation eingesetzt. Die aPTT als POCT ist teilweise problematisch, deren Einsatz muß kritisch erwogen werden. Der PFA-100-Analyser ist geeignet als Screeningtest für Thrombozytopathien und ausgeprägte Von-Willebrand-Faktor-Mangelzustände. Die D-Dimer-Teste mit Vollblut erfüllen die Anforderungen bezüglich hoher Sensitivität nicht immer.Die Einsatzmöglichkeiten der Hämostase-POCT-Analysen müssen kritisch und wissenschaftlich definiert werden. Diverse Aspekte wie Qualitätskontrolle, Kosten und Gewinnung der Vollblut-Proben müssen weiter bearbeitet werden.

scholarly journals COVID-19: The Rollercoaster of Fibrin(ogen), D-dimer, von Willebrand Factor, P-selectin and Their Interactions with Endothelial Cells, Platelets and Erythrocytes

2020 ◽  
Author(s):  
Corlia Grobler ◽  
Jhade Bredenkamp ◽  
Mireille Grobbelaar ◽  
Sipho Maphumulo ◽  
Jaco Laubscher ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Von Willebrand Factor ◽  
Poor Prognosis ◽  
Point Of Care ◽  
Platelet Dysfunction ◽  
Multiple Risk Factors ◽  
Low Levels ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
D Dimer

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), coronavirus disease 2019 (COVID-19)-induced infection is strongly associated with various coagulopathies that may result in either bleeding and thrombocytopenia or hypercoagulation and thrombosis. Thrombotic and bleeding or thrombotic pathologies are significant accompaniments to acute respiratory syndrome and lung complications in COVID-19. Thrombotic events and bleeding, often occurs in subjects with weak multiple risk factors and co-morbidities. Of particular interest are the various circulating inflammatory coagulation biomarkers involved directly in clotting, with specific focus on fibrin(ogen), D-dimer, P-selectin and von Willebrand Factor (vWF). Central to activity of these biomarkers are their receptors and signaling pathways on endothelial cells, platelets and erythrocytes. In this review, we discuss vascular implications of COVID-19, and relate this to circulating biomarker, endothelial, erythrocyte and platelet dysfunction. During the progression of the disease, these markers may either be within healthy levels, upregulated or eventually depleted. Most significant is that patients need to be treated early in the disease progression, when high levels of vWF, P-selectin and fibrinogen are present with still low levels of D-dimer. Progression to vWF and fibrinogen depletion with high D-dimer levels and even higher P-selectin levels, followed by the cytokine storm, will be indicative of a poor prognosis. We conclude by looking at point-of-care devises and methodologies in COVID-19 management and suggest that a personalized medicine approach should be considered in the treatment of patients.

CT-ADP Point-of-Care Assay Predicts 30-Day Paravalvular Aortic Regurgitation and Bleeding Events following Transcatheter Aortic Valve Replacement

2018 ◽  
Vol 118 (05) ◽  
pp. 893-905 ◽  
Author(s):  
Marion Kibler ◽  
Benjamin Marchandot ◽  
Nathan Messas ◽  
Thibault Caspar ◽  
Flavien Vincent ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Valve Replacement ◽  
Transcatheter Aortic Valve Replacement ◽  
Independent Predictor ◽  
Point Of Care ◽  
Major Life ◽  
Transcatheter Aortic Valve ◽  
Life Threatening ◽  
Von Willebrand

Background Paravalvular aortic regurgitation (PVAR) remains a frequent postprocedural concern following transcatheter aortic valve replacement (TAVR). Persistence of flow turbulence results in the cleavage of high-molecular-weight von Willebrand multimers, primary haemostasis dysfunction and may favour bleedings. Recent data have emphasized the value of a point-of-care measure of von Willebrand factor–dependent platelet function (closure time [CT] adenosine diphosphate [ADP]) in the monitoring of immediate PVAR. This study examined whether CT-ADP could detect PVAR at 30 days and bleeding complications following TAVR. Methods CT-ADP was assessed at baseline and the day after the procedure. At 30 days, significant PVAR was defined as a circumferential extent of regurgitation more than 10% by transthoracic echocardiography. Events at follow-up were assessed according to the Valve Academic Research Consortium-2 consensus classification. Results Significant PVAR was diagnosed in 44 out of 219 patients (20.1%). Important reduction of CT-ADP could be found in patients without PVAR, contrasting with the lack of CT-ADP improvement in significant PVAR patients. By multivariate analysis, CT-ADP > 180 seconds (hazard ratio [HR]: 5.1, 95% confidence interval [CI]: 2.5–10.6; p < 0.001) and a self-expandable valve were the sole independent predictors of 30-day PVAR. At follow-up, postprocedural CT-ADP >180 seconds was identified as an independent predictor of major/life-threatening bleeding (HR: 1.7, 95% CI [1.0–3.1]; p = 0.049). Major/life-threatening bleedings were at their highest levels in patients with postprocedural CT-ADP > 180 seconds (35.2 vs. 18.8%; p = 0.013). Conclusion Postprocedural CT-ADP > 180 seconds is an independent predictor of significant PVAR 30 days after TAVR and may independently contribute to major/life-threatening bleedings.

Evaluation of a modified thromboelastography assay for the screening of von Willebrand disease

2011 ◽  
Vol 105 (06) ◽  
pp. 1091-1099 ◽  
Author(s):  
Hans-Georg Topf ◽  
Dominik Weiss ◽  
Grischa Lischetzki ◽  
Erwin Strasser ◽  
Wolfgang Rascher ◽  
...  
Keyword(s):  
Point Of Care ◽  
Area Under The Curve ◽  
Maximum Amplitude ◽  
Von Willebrand Disease ◽  
Infusion Therapy ◽  
Clot Strength ◽  
Point Of Care Test ◽  
Diagnosis And Classification ◽  
Patient Groups ◽  
Von Willebrand

SummaryThromboelastography (TEG) has been shown to be a valuable point-of-care device for the rapid diagnosis of various bleeding disorders. However, TEG has thus far not been used for the screening for von Willebrand disease (VWD). We evaluated the performance of a modified TEG assay for the laboratory screening of VWD. Three hundred twenty-eight patients (148 male, 180 female, median age 8.4 years, range 0.1 – 72.7 years) were included in the study. The diagnosis and classification of patients was based on personal and familial case history, von Willebrand factor antigen, ristocetin cofactor levels, collagen binding assay, factor VIII coagulant activity and multimer analysis. The ratio of clot strength after preincubation with ristocetin, and without ristocetin, represents the component of clot strength that is formed by cross-linked fibrin fibres and is dependent on the agglutinated platelet fraction. The decrease of the maximum amplitude is a function of the ristocetin concentration and provides a diagnostic parameter able to differentiate between healthy individuals and patients having VWD. Based on a preliminary cut-off value of 25% for the area under the curve (AUC) ratio, the sensitivity varied from 53% to 100% for the different VWD patient groups. The test is suitable for use as a screening test using whole blood and has the additional benefit of being suitable as a point of care test. It appears also useful for monitoring responses to desmopressin (DDAVP) and infusion therapy.

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