177 results on '"Lorenzo Alberio"'
Search Results
2. Shall we rethink the timing of epidural anesthesia in anticoagulated obstetrical patients?
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Hélène Legardeur, Alexia Cuenoud, Alice Panchaud, Francesco Grandoni, Ana Batista Mesquita Sauvage, Lorenzo Alberio, David Baud, and Mathilde Gavillet
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360 Soziale Probleme, Sozialdienste ,Obstetrics and Gynecology ,610 Medizin und Gesundheit - Published
- 2023
3. Perioperative Management of a Patient With Combined Bernard Soulier syndrome and Storage Pool Disease During On-Pump Cardiac Surgery
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Emeline Christophel-Plathier, Mariangela Costanza, Matthias Kirsch, Filip Dulguerov, Catherine Chapuis-Bernasconi, Bettina Bisig, François Verdy, Vitor Mendes, Valentina Rancati, Lorenzo Alberio, Carlo Marcucci, and Emmanuelle Scala
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Anesthesiology and Pain Medicine ,Cardiology and Cardiovascular Medicine - Published
- 2023
4. Comparative analysis of automated cell counts in oncological patients: Reliable results of point of care blood impedance measurements and pitfalls in <scp>myelodysplastic neoplasias and acute myeloid leukemias</scp>
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Sabine Blum, Mariangela Costanza, Christine Coutaz, Olaia Naveiras, Olivier Spertini, Gerasimos Tsilimidos, and Lorenzo Alberio
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Biochemistry (medical) ,Clinical Biochemistry ,Hematology ,General Medicine - Published
- 2023
5. Identification of high platelet reactivity despite P2Y12 inhibitor treatment: Two populations in the VASP assay and variable PFA-P2Y shapes of curve
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Cyril Mariethoz, Emmanuelle Scala, Elena Matthey-Guirao, Jean-Benoît Rossel, Francisco J. Gomez, Francesco Grandoni, Carlo Marcucci, and Lorenzo Alberio
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Economics and Econometrics ,Materials Chemistry ,Media Technology ,Forestry - Abstract
Introduction Response to ADP P2Y12 receptor inhibition by clopidogrel can be evaluated by various techniques. Here, we compared a functional rapid point-of-care technique (PFA-P2Y®) with the degree of biochemical inhibition assessed by the VASP/P2Y12® assay. Methods Platelet response to clopidogrel was investigated in 173 patients undergoing elective intracerebral stenting (derivation cohort n=117; validation cohort n=56). High platelet reactivity (HPR) was defined as PFA-P2Y® occlusion time 50%. Results In the derivation cohort, ROC analysis for the ability of PFA-P2Y® to detect biochemical HPR showed high specificity (98.4%) but poor sensitivity (20.0%) and a very low AUC (0.59). The VASP/P2Y12® assay revealed two coexisting platelet populations with different levels of VASP phosphorylation: a fraction of highly phosphorylated, inhibited platelets and another of poorly phosphorylated, reactive platelets. Analysis of the PFA-P2Y® curve shape revealed different types, categorized by time of occlusion (300 sec) and pattern (regular, irregular, atypical). Noteworthy, curves with late occlusion and permeable curves with an irregular or atypical pattern correlated with VASP-PRI >50% and smaller sizes of the inhibited platelet sub-population. Considering the PFA-P2Y® shape of curve for the detection of HPR improved sensitivity (72.7%) and preserved specificity (91.9%), with a rather high AUC (0.823). The validation cohort confirmed the VASP/P2Y12® assay data and the usefulness of considering the PFA-P2Y® curve shape. Conclusion In patients treated with acetyl-salicylic acid and clopidogrel for 7-10 days, the VASP/P2Y12® assay reveals two coexisting sub-populations of differentially inhibited platelets, whose relative sizes predict global PRI and distinct PFA-P2Y® curve patterns. The detailed analysis of both VASP/P2Y12® and PFA-P2Y® is necessary for an optimal detection of HPR.
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- 2023
6. Caplacizumab for treating subacute intra-stent thrombus occurring despite efficacious double anti-platelet treatment and anticoagulation: a case report
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Gregoire Stalder, Antoine Chatte, Noemy De Rossi, Patrick Yerly, Lorenzo Alberio, Eric Eeckhout, Vrachatis, Dimitrios A (ed.), Gragnano, Felice (ed.), Hartley, Adam (ed.), Cankovic, Milenko Zoran (ed.), Spinthakis, Nikolaos (ed.), and Waight, Michael (ed.)
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Cardiology and Cardiovascular Medicine ,Caplacizumab ,Case Report ,N-acetylcysteine ,STEMI ,Subacute stent thrombosis ,von Willebrand factor - Abstract
BackgroundAcute and subacute stent thromboses are a rare complication associated with high mortality and morbidity occurring in ∼1.5% of patients treated with primary percutaneous intervention for ST-elevation myocardial infarction (STEMI). Recent publications describe a potential role of the von Willebrand factor (VWF) in thrombus formation at sites of critical coronary stenosis in STEMI.Case summaryWe describe a 58-year-old woman with STEMI at initial presentation, who suffered subacute stent thrombosis despite good stent expansion, efficacious dual antiplatelet therapy, and therapeutic anticoagulation. Because of very high VWF values, we administered N-acetylcysteine in order to depolymerize VWF, but the drug was not well tolerated. Since the patient was still symptomatic, we used caplacizumab in order to prevent VWF from interacting with platelets. Under this treatment, the clinical and angiographic course was favourable.DiscussionConsidering a modern view of intracoronary thrombus pathophysiology, we describe an innovative treatment approach, which eventually ended in a favourable outcome.
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- 2023
7. Thrombophilia and outcomes of venous thromboembolism in older patients
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Marie Méan, Neal Breakey, Odile Stalder, Lorenzo Alberio, Andreas Limacher, Anne Angelillo-Scherrer, Pierre Fontana, Hans Jürg Beer, Nicolas Rodondi, Drahomir Aujesky, Bernhard Lämmle, and Robert Escher
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360 Social problems & social services ,360 Soziale Probleme, Sozialdienste ,610 Medicine & health ,Hematology ,610 Medizin und Gesundheit - Abstract
BACKGROUND Limited data exist on thrombophilic risk factors and clinical outcomes in the elderly with venous thromboembolism (VTE). OBJECTIVES To describe the prevalence of laboratory thrombophilic risk factors and their association with VTE recurrence or death in a cohort of elderly people with VTE. METHODS In 240 patients aged ≥65 years with acute VTE without active cancer or an indication for extended anticoagulation, we performed laboratory thrombophilia testing 1 year after the index VTE. Recurrence or death was assessed during the 2-year follow-up. RESULTS A total of 78% of patients had ≥1 laboratory thrombophilic risk factor(s). Elevated levels of von Willebrand factor, homocysteine, coagulant activity of factor VIII (FVIII:C), fibrinogen, FIX:C, and low antithrombin activity were the most prevalent risk factors (43%, 30%, 15%, 14%, 13%, and 11%, respectively). Additionally, 16.2% of patients experienced VTE recurrence and 5.8% of patients died. Patients with a von Willebrand factor of >182%, FVIII:C level >200%, homocysteine level >15μmol/L, or lupus anticoagulant had a significantly higher rate of recurrence than those without these risk factors (15.0 vs. 6.1 [P = .006], 23.5 vs. 8.2 [P = .01], 17.0 vs. 6.8 [P = .006], and 89.5 vs. 9.2 [P = .02] events per 100 patient-years, respectively). Furthermore, patients with a high fibrinogen level or hyperhomocysteinemia with a homocysteine level ≥30 μmol/L had significantly higher mortality than patients with normal levels (18.5 vs. 2.8 [P = .049] and 13.6 vs. 2 [P = .002] deaths per 100 patient-years, respectively). After adjustments for relevant confounders, these associations remained unchanged. CONCLUSION Laboratory thrombophilic risk factors are common in elderly people with VTE and allow for the identification of a population at the risk of worse clinical outcomes.
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- 2023
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8. Managing argatroban in heparin‐induced thrombocytopenia: A retrospective analysis of 729 treatment days in 32 patients with confirmed heparin‐induced thrombocytopenia
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Matteo Marchetti, Stefano Barelli, Tobias Gleich, Francisco J. Gomez, Matthew Goodyer, Francesco Grandoni, and Lorenzo Alberio
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Sulfonamides ,Heparin ,Pipecolic Acids ,Anticoagulants ,Humans ,Anticoagulants/adverse effects ,Arginine/analogs & derivatives ,Heparin/adverse effects ,Pipecolic Acids/therapeutic use ,Retrospective Studies ,Sulfonamides/adverse effects ,Thrombocytopenia/chemically induced ,Thrombocytopenia/drug therapy ,anticoagulation ,argatroban ,argatroban monitoring ,heparin-induced thrombocytopenia ,plasmatic argatroban concentration ,Hematology ,Arginine ,Thrombocytopenia - Published
- 2022
9. A case of livedoid vasculopathy, a thrombotic occlusive vasculopathy
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Anais Huot, Christa‐Maria Maniu, Sofia Bogiatzi, Daniel Hohl, Lorenzo Alberio, and Gregoire Stalder
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- 2022
10. Erratum: Gentherapie der Hämophilie: Empfehlung der Gesellschaft für Thrombose- und Hämostaseforschung (GTH)
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Wolfgang, Miesbach, Johannes, Oldenburg, Robert, Klamroth, Hermann, Eichler, Jürgen, Koscielny, Susanne, Holzhauer, Katharina, Holstein, Johanna A Kremer, Hovinga, Lorenzo, Alberio, Martin, Olivieri, Ralf, Knöfler, Christoph, Male, and Andreas, Tiede
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Hematology - Published
- 2022
11. Long-standing thrombocytosis often precedes thromboembolic complications heralding the diagnosis of essential thrombocythemia
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Gregoire Stalder, William Reis Da Silva, Amandine Segot, Sabine Blum, Francesco Grandoni, and Lorenzo Alberio
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Thrombocytosis ,Platelet Count ,PMF ,Research ,MPN ,food and beverages ,Thrombosis ,PV ,Major bleeding ,Anticoagulation ,Thromboembolism ,Internal Medicine ,Humans ,MPN-U ,ET ,Thrombocythemia, Essential - Abstract
Background Patients with Ph-negative myeloproliferative neoplasms (MPN), such as polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are at increased risk for thrombosis/thromboembolism and major bleeding. Due to the morbidity and mortality of these events, antiplatelet and/or anticoagulant agents are commonly employed as primary and/or secondary prophylaxis. On the other hand, disease-related bleeding complications (i.e., from esophageal varices) are common in patients with MPN. This analysis was performed to define the frequency of such events, identify risk factors, and assess antiplatelet/anticoagulant therapy in a cohort of patients with MPN. Methods The MPN registry of the Study Alliance Leukemia is a non-interventional prospective study including adult patients with an MPN according to WHO criteria (2008). For statistical analysis, descriptive methods and tests for significant differences as well as contingency tables were used to identify the odds of potential risk factors for vascular events. Results MPN subgroups significantly differed in sex distribution, age at diagnosis, blood counts, LDH levels, JAK2V617F positivity, and spleen size (length). While most thromboembolic events occurred around the time of MPN diagnosis, one third of these events occurred after that date. Splanchnic vein thrombosis was most frequent in post-PV-MF and MPN-U patients. The chance of developing a thromboembolic event was significantly elevated if patients suffered from post-PV-MF (OR 3.43; 95 % CI = 1.39–8.48) and splenomegaly (OR 1.76; 95 % CI = 1.15–2.71). Significant odds for major bleeding were previous thromboembolic events (OR = 2.71; 95 % CI = 1.36–5.40), splenomegaly (OR = 2.22; 95 % CI 1.01–4.89), and the administration of heparin (OR = 5.64; 95 % CI = 1.84–17.34). Major bleeding episodes were significantly less frequent in ET patients compared to other MPN subgroups. Conclusions Together, this report on an unselected “real-world” cohort of German MPN patients reveals important data on the prevalence, diagnosis, and treatment of thromboembolic and major bleeding complications of MPN.
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- 2022
12. Two novel platelet biotinylation methods and their impact on stored platelet concentrates in a blood bank environment
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Charlotte Muret, David Crettaz, Agathe Martin, Alessandro Aliotta, Debora Bertaggia Calderara, Lorenzo Alberio, and Michel Prudent
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Blood Platelets ,Blood Preservation ,Immunology ,Immunology and Allergy ,Humans ,Blood Banks ,Biotin ,Biotinylation ,Hematology ,Platelet Transfusion - Abstract
Storage of platelet concentrates (PCs) has an impact on platelet quality and possibly affects their functions after transfusion. The influence of processing and storage conditions of PCs on their in vivo function upon transfusion is unknown. One option for investigating this question is to implement an ex vivo labeling of human platelets, to analyze them after transfusion into heathy volunteers and/or patients. In this study, we developed two labeling methods employing biotin.Two methods of biotinylation were compared to a control (standard PC). The "Bio-Wash" process used washing steps to label all platelets within the PC; for the other method, "Bio-Direct," one fifth of the PC were directly labeled without washing steps. The control and the two biotinylated PCs were analyzed over 7 days of storage. Labeling efficiency, platelet counts, phenotypes, and functions, along with time and costs, were evaluated to select the best process.Both methods achieved a stable labeling through the storage, with similar platelet counts and metabolism in comparison to control PCs. Bio-Wash showed higher activation phenotype and lower aggregation response in comparison to the Bio-Direct method. The Bio-Direct was performed within 1.5 h versus 3 h for the Bio-Wash. However, the Bio-Direct required 12 mg of biotin instead of 8 mg for the other process.We set up two methods of biotinylation that can be easily implemented in a blood bank environment. The Bio-Direct process was preferred to the Bio-Wash because of its similarity, from a functional and phenotypic point of view, with standard PCs.
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- 2022
13. COVID-19: SARS-CoV-2 Vaccine-Induced Immune Thrombotic Thrombocytopenia
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Rüdiger E. Scharf and Lorenzo Alberio
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2019-20 coronavirus outbreak ,COVID-19 Vaccines ,Coronavirus disease 2019 (COVID-19) ,Platelet Count ,SARS-CoV-2 ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,COVID-19 ,Thrombosis ,Hematology ,Thrombocytopenia ,Virology ,Immune system ,Humans ,Medicine ,Platelet ,business - Published
- 2021
14. Prothrombinase-Induced Clotting Time to Measure Drug Concentrations of Rivaroxaban, Apixaban, and Edoxaban in Clinical Practice: A Cross-Sectional Study
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Vepusha, Sathanantham, Lorenzo, Alberio, Cédric, Bovet, Pierre, Fontana, Bernhard, Gerber, Lukas, Graf, Adriana, Mendez, Thomas C, Sauter, Adrian, Schmidt, Jan-Dirk, Studt, Walter A, Wuillemin, and Michael, Nagler
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Prothrombinase-induced clotting time (PiCT) is proposed as a rapid and inexpensive laboratory test to measure direct oral anticoagulant (DOAC) drug levels. In a prospective, multicenter cross-sectional study, including 851 patients, we aimed to study the accuracy of PiCT in determining rivaroxaban, apixaban, and edoxaban drug concentrations and assessed whether clinically relevant drug levels could be predicted correctly. Citrated plasma samples were collected, and the Pefakit
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- 2022
15. Combinations of rapid immunoassays for a speedy diagnosis of heparin-induced thrombocytopenia
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Elena Matthey-Guirao, Lorenzo Alberio, Francesco Grandoni, Francisco Gomez, Matteo Marchetti, and Luana Rittener-Ruff
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Immunoassay ,Latex ,Heparin ,Immunoglobulin G ,Anticoagulants ,Humans ,Bayes Theorem ,Hematology ,Platelet Factor 4 ,Thrombocytopenia ,Retrospective Studies - Abstract
Early recognition and treatment of heparin-induced thrombocytopenia (HIT) are key to prevent severe complications.To assess the diagnostic performance of rapid immunoassays (IA) in detecting anti-PF4/heparin-antibodies.Diagnostic performances of lateral-flow IA (LFIA; STic Expert HIT) and latex IA (LIA; HemosIL HIT-Ab) were analyzed in pilot (n = 74) and derivation cohorts (n = 267). Two novel algorithms based on the combination of HIT clinical probability with sequentially performed LIA and chemiluminescent IA (CLIA; HemosIL AcuStar-HIT-IgG) were compared with published rapid diagnostic algorithms: the "Lausanne algorithm" sequentially combining CLIA and particle-gel IA (PaGIA) and the "Hamilton algorithm" based on simultaneously performed LIA and CLIA.LFIA missed 6/30 HIT. The sensitivity and specificity of LIA were 90.9% and 93.5%. The Lausanne algorithm correctly predicted HIT in 19/267 (7.1%), excluded it in 240/267 (89.9%), leaving 8/267 (3%) cases unsolved. The algorithm sequentially combining CLIA and LIA predicted HIT in 19/267 (7.1%) with 1/19 wrong prediction, excluded it in 236/267 (88.4%), leaving 11/267 (4.1%) cases unsolved. The algorithm employing LIA as a first assay predicted HIT in 22/267 (8.2%), excluded it in 235/267 (88%), leaving 9/267 (3.4%) cases unsolved. Finally, the Hamilton algorithm correctly predicted HIT in 10/267 (3.7%), excluded it in 229/267 (85.7%), leaving 28/267 (10.5%) cases unsolved.LFIA cannot be used to exclude or predict HIT when using frozen plasma. A Bayesian approach sequentially employing two rapid immunoassays for anti-PF4/heparin antibodies is most effective for the accurate diagnosis of HIT. Based on retrospective data, the combination LIA/CLIA is a candidate for a prospective validation.
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- 2022
16. High-Dose Epinephrine Enhances Platelet Aggregation at the Expense of Procoagulant Activity
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Maxime G. Zermatten, Alessandro Aliotta, Lorenzo Alberio, and Debora Bertaggia Calderara
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Adult ,Blood Platelets ,Male ,Agonist ,Adolescent ,Epinephrine ,Platelet Aggregation ,Fibrinogen receptor ,medicine.drug_class ,Receptors, Proteinase-Activated ,Platelet Membrane Glycoproteins ,030204 cardiovascular system & hematology ,Pharmacology ,Flow cytometry ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Thrombin ,Crotalid Venoms ,medicine ,Humans ,Lectins, C-Type ,Platelet ,Calcium Signaling ,Platelet activation ,Receptor ,Blood Coagulation ,Aged ,Dose-Response Relationship, Drug ,medicine.diagnostic_test ,Coagulants ,Chemistry ,Convulxin ,Hematology ,Middle Aged ,Kinetics ,Female ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Platelet activation is characterized by shape change, granule secretion, activation of fibrinogen receptor (glycoprotein IIb/IIIa) sustaining platelet aggregation, and externalization of negatively charged aminophospholipids contributing to platelet procoagulant activity. Epinephrine (EPI) alone is a weak platelet activator. However, it is able to potentiate platelet activation initiated by other agonists. In this work, we investigated the role of EPI in the generation of procoagulant platelets. Human platelets were activated with convulxin (CVX), thrombin (THR) or protease-activated receptor (PAR) agonists, EPI, and combination thereof. Platelet aggregation was assessed by light transmission aggregometry or with PAC-1 binding by flow cytometry. Procoagulant collagen-and-THR (COAT) platelets, induced by combined activation with CVX-and-THR, were visualized by flow cytometry as Annexin-V-positive and PAC-1-negative platelets. Cytosolic calcium fluxes were monitored by flow cytometry using Fluo-3 indicator. EPI increased platelet aggregation induced by all agonist combinations tested. On the other hand, EPI dose-dependently reduced the formation of procoagulant COAT platelets generated by combined CVX-and-THR activation. We observed a decreased Annexin-V-positivity and increased binding of PAC-1 with the triple activation (CVX + THR + EPI) compared with CVX + THR. Calcium mobilization with triple activation was decreased with the higher EPI dose (1,000 µM) compared with CVX + THR calcium kinetics. In conclusion, when platelets are activated with CVX-and-THR, the addition of increasing concentrations of EPI (triple stimulation) modulates platelet response reducing cytosolic calcium mobilization, decreasing procoagulant activity, and enhancing platelet aggregation.
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- 2021
17. Acquired haemophilia A in the postpartum and risk of relapse in subsequent pregnancies: A systematic literature review
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Lorenzo Alberio, Sabine Blum, Natacha Dewarrat, Francesco Grandoni, Mathilde Gavillet, Olaia Naveiras, Anne Angelillo-Scherrer, and Dimitrios A. Tsakiris
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medicine.medical_specialty ,Haemophilia A ,Disease ,030204 cardiovascular system & hematology ,Hemophilia A ,Haemophilia ,Hemostatics ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Recurrence ,Humans ,Medicine ,610 Medicine & health ,Genetics (clinical) ,Factor VIII ,business.industry ,Obstetrics ,Postpartum Period ,Hematology ,General Medicine ,medicine.disease ,Systematic review ,Female ,Rituximab ,Fresh frozen plasma ,business ,Postpartum period ,030215 immunology ,medicine.drug - Abstract
BACKGROUND About 1%-5% of acquired haemophilia A cases affect mothers in the postpartum setting. AIMS This study delineates the characteristics of this disease, specific to the postpartum setting, notably relapse in subsequent pregnancies. METHODS Report of two cases and literature study (1946-2019), yielding 73 articles describing 174 cases (total 176 cases). RESULTS Patients were aged 29.9 years (17-41) and 69% primigravidae. Diagnosis was made at a median of 60 days after delivery (range 0-308). Bleeding types were obstetrical (43.4%), cutaneous (41.3%), and muscular (36.7%). In >90% of the cases, FVIII at diagnosis was
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- 2021
18. Maladie thromboembolique veineuse et grossesse : diagnostic, traitement et suivi
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Matteo Vecchio, Cécile Guenot, Samuel Staubli, Mathilde Gavillet, Lorenzo Alberio, Lucia Mazzolai, and Adriano Alatri
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General Medicine - Published
- 2021
19. How to Solve the Conundrum of Heparin-Induced Thrombocytopenia during Cardiopulmonary Bypass
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Etienne Revelly, Emmanuelle Scala, Lorenzo Rosner, Valentina Rancati, Ziyad Gunga, Matthias Kirsch, Zied Ltaief, Marco Rusca, Xavier Bechtold, Lorenzo Alberio, and Carlo Marcucci
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General Medicine - Abstract
Heparin-induced thrombocytopenia (HIT) is a major issue in cardiac surgery requiring cardiopulmonary bypass (CPB). HIT represents a severe adverse drug reaction after heparin administration. It consists of immune-mediated thrombocytopenia paradoxically leading to thrombotic events. Detection of antibodies against platelets factor 4/heparin (anti-PF4/H) and aggregation of platelets in the presence of heparin in functional in vitro tests confirm the diagnosis. Patients suffering from HIT and requiring cardiac surgery are at high risk of lethal complications and present specific challenges. Four distinct phases are described in the usual HIT timeline, and the anticoagulation strategy chosen for CPB depends on the phase in which the patient is categorized. In this sense, we developed an institutional protocol covering each phase. It consisted of the use of a non-heparin anticoagulant such as bivalirudin, or the association of unfractionated heparin (UFH) with a potent antiplatelet drug such as tirofiban or cangrelor. Temporary reduction of anti-PF4 with intravenous immunoglobulins (IvIg) has recently been described as a complementary strategy. In this article, we briefly described the pathophysiology of HIT and focused on the various strategies that can be applied to safely manage CPB in these patients.
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- 2023
20. Sodium–Calcium Exchanger Reverse Mode Sustains Dichotomous Ion Fluxes Required for Procoagulant COAT Platelet Formation
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Lorenzo Alberio, Maxime G. Zermatten, Debora Bertaggia Calderara, and Alessandro Aliotta
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Blood Platelets ,0301 basic medicine ,Sodium ,chemistry.chemical_element ,030204 cardiovascular system & hematology ,Calcium ,Sodium-Calcium Exchanger ,Calcium in biology ,03 medical and health sciences ,0302 clinical medicine ,Humans ,Platelet ,Platelet activation ,Blood Coagulation ,Calcium metabolism ,Ion Transport ,Sodium-calcium exchanger ,Thrombin ,Hematology ,Platelet Activation ,030104 developmental biology ,chemistry ,Potassium ,Biophysics ,Collagen ,Intracellular - Abstract
Procoagulant collagen-and-thrombin (COAT)-activated platelets represent a subpopulation of activated platelets, which retain a coat of prohemostatic proteins and express phosphatidylserine on their surface. Dichotomous intracellular signaling generating procoagulant platelet activity instead of traditional aggregating endpoints is still not fully elucidated. It has been demonstrated that secondary messengers such as calcium and sodium play a critical role in platelet activation. Therefore, we developed a flow cytometric analysis to investigate intracellular ion fluxes simultaneously during generation of aggregating and procoagulant platelets. Human platelets were activated by convulxin-plus-thrombin. Cytosolic calcium, sodium, and potassium ion fluxes were visualized by specific ion probes and analyzed by flow cytometry. We observed high and prolonged intracellular calcium concentration, transient sodium increase, and fast potassium efflux in COAT platelets, whereas aggregating non-COAT platelets rapidly decreased their calcium content, maintaining higher cytosolic sodium, and experiencing lower and slower potassium depletion. Considering these antithetical patterns, we investigated the role of the sodium–calcium exchanger (NCX) during convulxin-plus-thrombin activation. NCX inhibitors, CBDMB and ORM-10103, dose-dependently reduced the global calcium mobilization induced by convulxin-plus-thrombin activation and dose-dependently prevented formation of procoagulant COAT platelets. Our data demonstrate that both NCX modes are used after convulxin-plus-thrombin-induced platelet activation. Non-COAT platelets use forward-mode NCX, thus pumping calcium out and moving sodium in, while COAT platelets rely on reverse NCX function, which pumps additional calcium into the cytosol, by extruding sodium. In conclusion, we described for the first time the critical and dichotomous role of NCX function during convulxin-plus-thrombin-induced platelet activation.
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- 2020
21. How to Capture the Bleeding Phenotype in FXI-Deficient Patients
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Maxime G. Zermatten, Alessandro Aliotta, Lorenzo Alberio, and Debora Bertaggia Calderara
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Thrombotic risk ,Research groups ,Factor XI Deficiency ,business.industry ,Fibrinolysis ,Thrombin ,Hematology ,Blood Coagulation Disorders ,Bioinformatics ,Phenotype ,Review article ,Coagulation ,Hemostasis ,Medicine ,Coagulation factor XI ,business ,Clinical phenotype - Abstract
Factor XI (FXI) is a serine protease involved in the propagation phase of coagulation and in providing clot stability. Several mutations in the F11 gene lead to FXI deficiency, a rare mild bleeding disorder. Current laboratory methods are unable to assess bleeding risk in FXI-deficient patients, because the degree of bleeding tendency does not correlate with plasma FXI activity as measured by routine coagulometric aPTT–based assays. Bleeding manifestations are highly variable among FXI-deficient patients and FXI replacement therapy can be associated with an increased thrombotic risk. A correct evaluation of the patient hemostatic potential is crucial to prevent under- or overtreatment. In recent years, different research groups have investigated the use of global coagulation assays as alternative for studying the role of FXI in hemostasis and identifying the clinical phenotype of FXI deficiency. This brief review article summarizes the main features of coagulation factor XI and its deficiency and resumes the principle axes of research and methods used to investigate FXI functions.
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- 2020
22. Another piece of knowledge in the puzzle of procoagulant COAT platelets
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Alessandro Aliotta and Lorenzo Alberio
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Blood Platelets ,Humans ,Platelet Activation ,Thrombin ,Hematology ,Corrigenda - Published
- 2022
23. Low COAT platelets are frequent in patients with bleeding disorders of unknown cause (BDUC) and can be enhanced by DDAVP
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Amandine Segot, Marcel Adler, Alessandro Aliotta, Elena Matthey‐Guirao, Michael Nagler, Debora Bertaggia Calderara, Francesco Grandoni, Francisco J. Gomez, and Lorenzo Alberio
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Blood Platelets ,Bleeding Time ,Blood Coagulation Disorders ,Deamino Arginine Vasopressin/therapeutic use ,Hemorrhagic Disorders ,Humans ,610 Medicine & health ,Deamino Arginine Vasopressin ,Hematology - Published
- 2022
24. Mechanisms Underlying Dichotomous Procoagulant COAT Platelet Generation-A Conceptual Review Summarizing Current Knowledge
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Lorenzo Alberio, Alessandro Aliotta, Cindy Pereira Portela, Debora Bertaggia Calderara, and Lucas Veuthey
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Blood Platelets ,Organic Chemistry ,Thrombin ,Thrombosis ,General Medicine ,Platelet Activation ,Catalysis ,Computer Science Applications ,Inorganic Chemistry ,Humans ,Calcium ,Physical and Theoretical Chemistry ,Molecular Biology ,Spectroscopy - Abstract
Procoagulant platelets are a subtype of activated platelets that sustains thrombin generation in order to consolidate the clot and stop bleeding. This aspect of platelet activation is gaining more and more recognition and interest. In fact, next to aggregating platelets, procoagulant platelets are key regulators of thrombus formation. Imbalance of both subpopulations can lead to undesired thrombotic or bleeding events. COAT platelets derive from a common pro-aggregatory phenotype in cells capable of accumulating enough cytosolic calcium to trigger specific pathways that mediate the loss of their aggregating properties and the development of new adhesive and procoagulant characteristics. Complex cascades of signaling events are involved and this may explain why an inter-individual variability exists in procoagulant potential. Nowadays, we know the key agonists and mediators underlying the generation of a procoagulant platelet response. However, we still lack insight into the actual mechanisms controlling this dichotomous pattern (i.e., procoagulant versus aggregating phenotype). In this review, we describe the phenotypic characteristics of procoagulant COAT platelets, we detail the current knowledge on the mechanisms of the procoagulant response, and discuss possible drivers of this dichotomous diversification, in particular addressing the impact of the platelet environment during in vivo thrombus formation.
- Published
- 2022
25. GTH 2021: The First Online Experience! Useful for Future Meetings?
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Lorenzo Alberio
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Education, Distance ,World Wide Web ,Computer science ,Humans ,Hematology ,Congresses as Topic ,History, 21st Century - Published
- 2021
26. The Art of Detecting Antibodies against Factor VIII
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Lorenzo Alberio and Andreas Tiede
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congenital, hereditary, and neonatal diseases and abnormalities ,Factor VIII ,biology ,business.industry ,animal diseases ,Autoantibody ,Hematology ,030204 cardiovascular system & hematology ,Antibodies, Neutralizing ,03 medical and health sciences ,0302 clinical medicine ,Coagulation ,hemic and lymphatic diseases ,Immunology ,biology.protein ,Acquired hemophilia ,Humans ,Medicine ,In patient ,Antibody ,business ,030215 immunology - Abstract
Antibodies against factor VIII (FVIII) can be detected based on their ability to neutralize the procoagulant activity of FVIII (neutralizing antibodies, inhibitors), or based on their specific binding capacity to FVIII protein. This article reviews the available assays and their clinical interpretation in patients with congenital and acquired hemophilia.Antikörper gegen Faktor VIII (FVIII) können anhand ihrer neutralisierenden Funktion gegenüber der prokoagulatorischen FVIII Aktivität oder anhand ihrer Bindung an das FVIII-Protein nachgewiesen werden. Dieser Artikel gibt einen Überblick über die verfügbaren Laborteste und ihre klinische Interpretation bei Patienten mit angeborener oder erworbener Hämophilie.
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- 2020
27. Flow Cytometric Monitoring of Dynamic Cytosolic Calcium, Sodium, and Potassium Fluxes Following Platelet Activation
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Lorenzo Alberio, Debora Bertaggia Calderara, and Alessandro Aliotta
- Subjects
Blood Platelets ,0301 basic medicine ,Agonist ,Histology ,medicine.drug_class ,Sodium ,Potassium ,chemistry.chemical_element ,Calcium ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Platelet ,Platelet activation ,Ion transporter ,Thrombin ,Convulxin ,Cell Biology ,Flow Cytometry ,Platelet Activation ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,Biophysics - Abstract
The interaction of platelet agonists with their respective membrane receptors triggers intracellular signaling, among which cytosolic ion fluxes play an important role in activation processes. While the key contribution of intercellular free calcium is accepted, sodium and potassium roles in platelet activation have been less investigated in recent studies. Here, we implemented a novel flow-cytometric method to monitor over time cytosolic free calcium, sodium, and potassium ion fluxes upon platelet activation and we demonstrate the feasibility of real-time visualization of ion kinetics, in particular with a focus on sodium and potassium. Platelets were loaded with selective ion indicators, Fluo-3 (Ca2+ ), ION NaTRIUM Green-2 (Na+ ), and ION Potassium Green-2 (K+ ). Fluorescence was monitored by flow cytometry. After measurement of a stable baseline, platelets were activated and ion indicator fluorescence was acquired over time, up to 10 min. Platelets were activated with either thromboxane analogue U46619, ADP, thrombin, TRAP6 (PAR-1 agonist), AYPGKF (PAR-4 agonist), convulxin (collagen receptor GPVI agonist), or combinations thereof. We evaluated preanalytical parameters (in particular dye loading time and concentration) to implement an accurate method. Subsequently, we characterized cytosolic calcium, sodium, and potassium kinetics in response to platelet agonists. We observed different patterns of agonist synergism. In conclusion, the present work highlights the use of cytosolic ion monitoring by flow cytometry to investigate characteristic calcium, sodium, and potassium mobilization patterns following platelet activation. This easy technique opens a new way to analyze signaling in different platelet subpopulations and it should prove useful for investigating platelet pathophysiology. © 2020 International Society for Advancement of Cytometry.
- Published
- 2020
28. Thrombin generation in a woman with heterozygous factor V Leiden and combined oral contraceptives: A case report
- Author
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Lorenzo Alberio, Maxime G. Zermatten, Debora Bertaggia Calderara, and Alessandro Aliotta
- Subjects
Proband ,medicine.medical_specialty ,Case Report ,Thrombomodulin ,Gastroenterology ,contraception ,factor V ,thrombin ,thromboembolism ,thrombosis ,venous ,Thrombin ,Internal medicine ,medicine ,Factor V Leiden ,biology ,lcsh:RC633-647.5 ,business.industry ,Factor V ,Combined oral contraceptives ,lcsh:Diseases of the blood and blood-forming organs ,Hematology ,medicine.disease ,Thrombosis ,Discontinuation ,biology.protein ,business ,medicine.drug - Abstract
Combined oral contraceptives and factor V Leiden mutation are multiplicative risk factors for venous thromboembolism. However, it remains unknown whether this multiplicative effect is reflected in thrombin generation assays. We report here the evolution of the thrombin generation profile while taking combined oral contraceptives and after their discontinuation in a woman with heterozygous factor V Leiden mutation. The proband exhibited a distinctly prothrombotic thrombin generation profile including markedly decreased thrombomodulin (TM) sensitivity, compared to the control population. This profile possibly reflected a high thrombotic risk. After discontinuation of combined oral contraceptives, thrombin generation and TM sensitivity improved greatly, leaving only a slightly prothrombotic profile. Therefore, the multiplied thrombotic risk occurring with simultaneous combined oral contraceptives and factor V Leiden mutation is reflected by a thrombin generation assay performed without and with TM. This could be a promising tool to identify women taking combined oral contraceptives at high risk for venous thromboembolism. Further studies are needed to verify this hypothesis.
- Published
- 2020
29. Comparison of ROTEM Sigma to Standard Laboratory Tests and Development of an Algorithm for the Management of Coagulopathic Bleeding in a Tertiary Center
- Author
-
Carlo Marcucci, Lorenzo Alberio, Christine Coutaz, Francisco Gomez, and Emmanuelle Scala
- Subjects
Hyperfibrinogenemia ,030204 cardiovascular system & hematology ,Tertiary Care Centers ,03 medical and health sciences ,Fibrinogen levels ,0302 clinical medicine ,Von willebrand ,030202 anesthesiology ,Coagulopathy ,medicine ,Humans ,Cutoff ,Receiver operating characteristic ,Clinical Laboratory Techniques ,business.industry ,Sigma ,Reference Standards ,medicine.disease ,Normal limit ,Thrombelastography ,Anesthesiology and Pain Medicine ,Blood Coagulation Tests ,Cardiology and Cardiovascular Medicine ,business ,Algorithm ,Algorithms - Abstract
Objective The ROTEM sigma whole blood viscoelastic test uses different technology than the former delta model. Existing ROTEM based algorithms use cutoff values based on the delta model, and cannot be applied to the sigma model. The authors tested sensitivity and specificity of ROTEM sigma parameters to detect specific hemostatic deficiencies and established cutoff values with the aim of developing a treatment algorithm. Design Prospective observational evaluation of diagnostic accuracy. Setting This study was performed in a tertiary center. Participants Blood samples for standard laboratory tests (SLTs) and ROTEM sigma analysis were obtained from 14 healthy volunteers and 35 patients showing various hemostatic disorders (isolated factor deficiencies, von Willebrand's disease, thrombocytopenia, hypofibrinogenemia, hyperfibrinogenemia, and patients undergoing cardiac surgery). Intervention Correlation coefficients were calculated between SLTs and ROTEM parameters in the extrinsic pathway activation, intrinsic pathway activation, and extrinsic pathway activation with platelet inhibition tests. Receiver operator characteristics defined the values of ROTEM parameters, which best predict plasma fibrinogen level measured by Clauss method 37 seconds and 1.5 times the upper normal limit. Measurement and Main Results The combination of FIBTEM A5 ≤12 mm and EXTEM A5 ≤44 mm identified a fibrinogen level 80 seconds had a 25.0% sensitivity and a 100% specificity for a PT 204 seconds showed a sensitivity of 75.0% and a specificity of 97.4% for an aPTT >37 and a sensitivity of 100% and a specificity of 80.0% for an aPTT >55 seconds. Conclusion The authors present the first ROTEM sigma-based algorithm for the treatment of coagulopathic bleeding. The algorithm uses parameters with optimal sensitivity and specificity for critical values of SLTs determined from a heterogenous group of donors.
- Published
- 2020
30. Potential and Limitations of the New P2Y12 Inhibitor, Cangrelor, in Preventing Heparin-Induced Platelet Aggregation During Cardiac Surgery: An In Vitro Study
- Author
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Carlo Marcucci, Emmanuelle Scala, Lorenzo Alberio, Francisco J Gomez, and Christiane Gerschheimer
- Subjects
medicine.medical_specialty ,Platelet Aggregation ,medicine.drug_class ,medicine.medical_treatment ,Pharmacology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Cangrelor ,P2Y12 ,030202 anesthesiology ,Interquartile range ,medicine ,Humans ,Cardiac Surgical Procedures ,Saline ,Heparin ,business.industry ,Anticoagulant ,Anticoagulants ,Adenosine Monophosphate ,Receptors, Purinergic P2Y12 ,Cardiac surgery ,Anesthesiology and Pain Medicine ,chemistry ,Bypass surgery ,Purinergic P2Y Receptor Antagonists ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Heparin-induced thrombocytopenia (HIT) can put cardiac surgery patients at a high risk of lethal complications. If anti-PF4/heparin antibodies (anti-PF4/Hep Abs) are present, 2 strategies exist to prevent intraoperative aggregation during bypass surgery: first, using an alternative anticoagulant, and second, using heparin combined with an antiaggregant. The new P2Y12 inhibitor, cangrelor, could be an attractive candidate for the latter strategy; several authors have reported its successful use. The present in vitro study evaluated cangrelor's ability to inhibit heparin-induced platelet aggregation in the presence of anti-PF4/Hep Abs.Platelet-poor plasma (PPP) from 30 patients with functional anti-PF4/Hep Abs was mixed with platelet-rich plasma (PRP) from 5 healthy donors.Light transmission aggregometry was used to measure platelet aggregation after adding 0.5 IU·mL of heparin (HIT) to the plasma, and this was compared with samples spiked with normal saline (control) and samples spiked with cangrelor 500 ng·mL and heparin 0.5 IU·mL (treatment). Friedman test with post hoc Dunn-Bonferroni test was used for between-group comparisons.Heparin 0.5 IU·mL triggered aggregation in 22 of 44 PPP-PRP mixtures, with a median aggregation of 86% (interquartile range [IQR], 69-91). The median aggregation of these 22 positive samples' respective control tests was 22% (IQR, 16-30) (P.001). Median aggregation in the cangrelor-treated samples was 29% (IQR, 19-54) and significantly lower than the HIT samples (P.001). Cangrelor inhibited heparin-induced aggregation by a median of 91% (IQR, 52-100). Cangrelor only reduced heparin-induced aggregation by95% in 10 of the 22 positive samples (45%). Cangrelor inhibited heparin-induced aggregation by50% in 5 of the 22 positive samples (22%) and by10% in 3 samples (14%).This in vitro study found that cangrelor was an unreliable inhibitor of heparin-induced aggregation in the presence of anti-PF4/Hep Abs. We conclude that cangrelor should not be used as a standard antiaggregant for cardiac patients affected by HIT during surgery. Unless cangrelor's efficacy in a particular patient has been confirmed in a presurgery aggregation test, other strategies should be chosen.
- Published
- 2020
31. Accuracy of heparin-induced platelet aggregation test for the diagnosis of heparin-induced thrombocytopenia
- Author
-
Lorenzo Alberio, Anne Angelillo-Scherrer, Michael Nagler, and Justine Brodard
- Subjects
medicine.medical_specialty ,Platelet Aggregation ,Enzyme-Linked Immunosorbent Assay ,030204 cardiovascular system & hematology ,Platelet Factor 4 ,Gastroenterology ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Heparin-induced thrombocytopenia ,Internal medicine ,medicine ,Humans ,Platelet ,Prospective Studies ,Platelet activation ,610 Medicine & health ,Heparin ,business.industry ,Hematology ,Gold standard (test) ,medicine.disease ,Thrombocytopenia ,Confidence interval ,030220 oncology & carcinogenesis ,business ,Platelet factor 4 ,Cohort study ,medicine.drug - Abstract
Introduction Whereas the utility of washed platelet assays such as the heparin-induced platelet activation test (HIPA) for the diagnosis of heparin-induced thrombocytopenia (HIT) is regarded as high, the performance of simpler assays such as the heparin-induced platelet aggregation test (PAT) is still elusive. Using well-characterized samples of a large cohort study, we aimed to assess the diagnostic accuracy of PAT for the diagnosis of HIT. Material and methods One-hundred twenty-two immunoassay-positive serum samples of a previous, prospective single-center cohort study including consecutive patients with suspected HIT (n = 1291) were used. HIPA was determined as reference gold standard; samples were previously analyzed using PAT as well as polyspecific platelet factor 4/heparin enzyme-linked immunosorbent assay (ELISA). 4Ts score was calculated using the patient documentation. Diagnosis of HIT was defined as a positive HIPA, which is a positive reaction in 2 out of 4 donor platelets within 30 min. Results HIT was diagnosed in 39 out of 122 patients corresponding to a prevalence of 32%. Median optical density (ELISA) was 2.8 (inter-quartile range 2.3, 3.0) in patients with HIT and 0.7 (0.5, 1.3) in patients without HIT. PAT was positive in 27 out of 39 HIT patients and it was negative in 83 out of 83 HIT-negative patients. Thus, the sensitivity of PAT for the diagnosis of HIT was 69% (95% confidence interval 52%, 83%) and the specificity 100% (96%, 100%). Conclusions Our results demonstrate that PAT is a valuable test to confirm HIT but cannot be applied to rule-out HIT in clinical practice.
- Published
- 2020
32. Multicentre evaluation of 5B9, a monoclonal anti-PF4/heparin IgG mimicking human HIT antibodies, as an internal quality control in HIT functional assays: Communication from the ISTH SSC Subcommittee on Platelet Immunology
- Author
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Lorenzo Alberio, Claire Pouplard, Dorothée Faille, Caroline Vayne, Nadine Azjenberg, Beng H. Chong, Zohra Ahmadi, Marie-Christine Morel-Kopp, Francisco-Javier Gomez, Noémie Charuel, James W. Smith, François Mullier, Brian R. Curtis, Yves Gruel, Paolo Gresele, Karina Althaus, Tamam Bakchoul, Jérôme Rollin, Andreas Greinacher, Izhac Nazy, UCL - SSS/IREC/MONT - Pôle Mont Godinne, and UCL - (MGD) Laboratoire de biologie clinique
- Subjects
Blood Platelets ,Quality Control ,medicine.drug_class ,standardisation ,Monoclonal antibody ,Platelet Factor 4 ,Heparin-induced thrombocytopenia ,Medicine ,Humans ,Platelet ,Platelet activation ,functional assays ,biology ,business.industry ,Heparin ,Communication ,Antibodies, Monoclonal ,Anticoagulants ,Hematology ,medicine.disease ,Platelet Activation ,Thrombocytopenia ,platelet factor 4 ,monoclonal antibody ,Immunoglobulin G ,Immunology ,Monoclonal ,biology.protein ,heparin-induced thrombocytopenia ,Antibody ,business ,Platelet factor 4 ,medicine.drug - Abstract
BACKGROUND: Functional tests for the diagnosis of heparin-induced thrombocytopenia (HIT) exhibit variable performance. OBJECTIVES: We evaluated in a multicenter study whether 5B9, a monoclonal anti-PF4/heparin IgG mimicking human HIT antibodies, could be used as an internal quality control. METHODS: 5B9 was sent to 11 laboratories in seven countries, and six initial concentrations ranging from 10 to 400 μg/mL were tested by heparin-induced platelet activation assay (HIPA), serotonin release assay (SRA), platelet aggregation test (PAT), flow cytometry (FC), or heparin-induced multiple-electrode aggregometry (HIMEA). Each method was evaluated in three different laboratories using experimental procedures identical to those usually applied for the diagnosis of HIT by testing platelets from 10 different healthy donors. RESULTS: The procedures used varied among the laboratories, particularly when platelet-rich plasma and whole blood were used. Nevertheless, positive results were obtained with at least 100 μg/ml of 5B9 for most donors tested by all centers (except one) performing HIPA, SRA, or HIMEA. FC and PAT results were more heterogeneous. FC results from one center that used washed platelets preincubated with PF4 were positive with all donors at 50 µg/ml 5B9, but at least 200 μg/ml of 5B9 were required to activate cells with most donors tested using PAT. CONCLUSION: This study confirms that HIT functional tests are not well standardized and exhibit variable sensitivity for the detection of platelet-activating antibodies. However, 5B9 is a potentially useful tool to standardize functional tests, to select responding platelet donors, and consequently to improve the performance of these assays and comparability between laboratories.
- Published
- 2021
33. Altered platelet functions during treatment with apremilast for psoriatic arthritis: A case report
- Author
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Gerasimos Tsilimidos, Sabine Blum, Alessandro Aliotta, Alexandre Dumusc, and Lorenzo Alberio
- Subjects
General Medicine ,General Biochemistry, Genetics and Molecular Biology - Published
- 2022
34. Epinephrine enhances platelet aggregation at the expense of procoagulant activity
- Author
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Maxime G. Zermatten, Alessandro Aliotta, Lorenzo Alberio, and D Bertaggia Calderara
- Subjects
Epinephrine ,Platelet aggregation ,Chemistry ,medicine ,Pharmacology ,medicine.drug - Published
- 2021
35. A universal anti-Xa assay for the determination of rivaroxaban, apixaban, and edoxaban drug levels: development, diagnostic accuracy, and external validation
- Author
-
JD Studt, WA Wuillemin, A Schmidt, G Willekens, B Gerber, Lorenzo Alberio, L. Graf, Pierre Fontana, Adriana Mendez, Cédric Bovet, and Michael Nagler
- Subjects
Oncology ,medicine.medical_specialty ,Rivaroxaban ,business.industry ,External validation ,Diagnostic accuracy ,Drug levels ,chemistry.chemical_compound ,chemistry ,Edoxaban ,Internal medicine ,medicine ,Apixaban ,business ,medicine.drug - Published
- 2021
36. Accuracy of the STA®-Liquid anti-Xa assay in clinical practice: results from a large cross-sectional study in Switzerland
- Author
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Adriana Mendez, Cédric Bovet, A Schmidt, Pierre Fontana, Lorenzo Alberio, L. Graf, B Gerber, Jan-Dirk Studt, S Naas, WA Wuillemin, and Michael Nagler
- Subjects
Clinical Practice ,medicine.medical_specialty ,business.industry ,Cross-sectional study ,Internal medicine ,Medicine ,business - Published
- 2021
37. Efficacy of direct oral anticoagulants in plasma from patients with liver cirrhosis at high thrombotic risk
- Author
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Montserrat Fraga, Lorenzo Alberio, Maxime G. Zermatten, Darius Moradpour, D Bertaggia Calderara, and Alessandro Aliotta
- Subjects
Thrombotic risk ,medicine.medical_specialty ,Cirrhosis ,business.industry ,Internal medicine ,Medicine ,business ,medicine.disease ,Gastroenterology - Published
- 2021
38. Usefulness of global assays to monitor treatment of a patient with Hemophilia A switching from factor to non-factor replacement therapy
- Author
-
Alessandro Aliotta, Lorenzo Alberio, D Bertaggia Calderara, and Maxime G. Zermatten
- Subjects
Oncology ,medicine.medical_specialty ,Factor replacement ,business.industry ,Internal medicine ,Medicine ,business - Published
- 2021
39. Evaluation of different processing methods to label platelets for in vivo studies
- Author
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Lorenzo Alberio, Michel Prudent, David Crettaz, C Muret, Alessandro Aliotta, D Bertaggia Calderara, Maxime G. Zermatten, and A Martin
- Subjects
In vivo ,Chemistry ,Platelet ,Biomedical engineering ,Processing methods - Published
- 2021
40. High levels of interleukine-6 in ascites prevent ascites reinfusion during hemodialysis
- Author
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Lorenzo Alberio, Montserrat Fraga, Jean-François Brunet, Fadi Fakhouri, Matthieu Halfon, Sébastien Kissling, Denis Comte, and Florent Artru
- Subjects
medicine.medical_specialty ,Hepatology ,business.industry ,Interleukin-6 ,medicine.medical_treatment ,Gastroenterology ,MEDLINE ,Ascites ,Text mining ,Renal Dialysis ,Internal medicine ,medicine ,Ascitic Fluid ,Humans ,Hemodialysis ,medicine.symptom ,business - Published
- 2021
41. EBV-positive large B-cell lymphoma with an unusual intravascular presentation and associated haemophagocytic syndrome in an HIV-positive patient: report of a case expanding the spectrum of EBV-positive immunodeficiency-associated lymphoproliferative disorders
- Author
-
Lorenzo Alberio, Luis Veloza, Chun-Yi Tsai, Laurence de Leval, Olivier Pantet, Christine Sempoux, Matthias Cavassini, and Bettina Bisig
- Subjects
Pathology ,medicine.medical_specialty ,Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,medicine.medical_treatment ,Lymphoproliferative disorders ,Spleen ,HIV Infections ,Lymphohistiocytosis, Hemophagocytic ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,immune system diseases ,Aged ,Epstein-Barr Virus Infections/complications ,Epstein-Barr Virus Infections/pathology ,HIV Infections/complications ,Humans ,Lymphohistiocytosis, Hemophagocytic/complications ,Lymphohistiocytosis, Hemophagocytic/etiology ,Lymphoma, Large B-Cell, Diffuse/complications ,Lymphoma, Large B-Cell, Diffuse/pathology ,Lymphoproliferative Disorders/pathology ,EBV ,HIV ,Haemophagocytic syndrome ,Hepatic capillary haemangioma ,Intravascular large B-cell lymphoma ,hemic and lymphatic diseases ,medicine ,B-cell lymphoma ,Molecular Biology ,Immunodeficiency ,business.industry ,Immunosuppression ,Cell Biology ,General Medicine ,medicine.disease ,Lymphoproliferative Disorders ,Lymphoma ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Bone marrow ,Lymphoma, Large B-Cell, Diffuse ,business ,030215 immunology - Abstract
Intravascular large B-cell lymphoma is a rare and aggressive EBV-negative large B-cell lymphoma with a dismal outcome. Here, we describe the case of a 76-year-old HIV-positive patient with an acute presentation of systemic symptoms and rapidly fatal outcome. Autopsy revealed a disseminated large B-cell lymphoma with an intravascular distribution involving the liver, lymph nodes, spleen, and bone marrow and associated to fibrin thrombi in hepatic capillary haemangiomas. The neoplastic B cells (CD79a + / − , CD20 + / − , CD30 + , MUM1 + , PD-L1 +) showed a Hodgkin and Reed-Sternberg-like morphology and were EBV-positive with a latency type II (LMP1 + , EBNA2-). Haemophagocytosis was documented in the bone marrow and lymph nodes. This case illustrates the diagnostic challenges of large B-cell lymphoma with intravascular presentation. We found only five other cases of EBV-positive large B-cell lymphoma with an intravascular presentation in the literature, three of which had an underlying immunodeficiency adding to the broad spectrum of EBV-associated lymphoma in the setting of immunosuppression.
- Published
- 2021
42. Nachweis von PF4/Heparin-Antikörpern
- Author
-
Lorenzo Alberio, Vanessa Kraege, and Noémie Parejas
- Abstract
Theoretischer Rahmen und klinische Anwendung der PF4/Heparin-Antikorper zur Diagnose von heparininduzierter Thrombozytopenie.
- Published
- 2021
43. Recherche d’anticorps anti-PF4/héparine
- Author
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Lorenzo Alberio, Noémie Parejas, and Vanessa Kraege
- Abstract
Cadre theorique et utilisation en clinique des anticorps anti-PF4/heparine dans le diagnostic d’une thrombopenie induite par l’heparine.
- Published
- 2021
44. Diagnostic utility of the ISTH bleeding assessment tool in patients with suspected platelet function disorders
- Author
-
Michael Nagler, Lorenzo Alberio, Jonas Kaufmann, and Marcel Adler
- Subjects
Adult ,Male ,medicine.medical_specialty ,blood platelet disorders/diagnosis ,hemorrhagic disorders/diagnosis ,Platelet Aggregation ,Platelet Function Tests ,610 Medicine & health ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Interquartile range ,Internal medicine ,medicine ,Humans ,Platelet ,In patient ,Prospective Studies ,Prospective cohort study ,Blood Platelet Disorders/blood ,Blood Platelet Disorders/diagnosis ,Female ,Flow Cytometry ,Middle Aged ,Predictive Value of Tests ,Reproducibility of Results ,platelet function tests ,predictive value of tests ,prognosis ,surveys and questionnaires ,Receiver operating characteristic ,business.industry ,Area under the curve ,Original Articles ,Hematology ,medicine.disease ,Thrombosis ,PLATELETS ,Predictive value of tests ,Original Article ,Blood Platelet Disorders ,business - Abstract
Essentials The utility of bleeding assessment tools regarding platelet function disorders is still elusive. We studied consecutive patients in a prospective cohort study in a tertiary hospital. Substantially higher scorings were observed in patients with platelet function disorders. Bleeding assessment tools might provide a useful screening tool. BACKGROUND Bleeding assessment tools (BATs) have been widely implemented in the evaluation of patients with suspected bleeding disorders. However, diagnostic BAT utility regarding platelet function disorders is still elusive. AIM We aimed to assess the diagnostic value of the International Society on Thrombosis and Haemostasis BAT (ISTH-BAT) for platelet function disorders in clinical practice. METHODS The clinical characteristics and laboratory data of all consecutive patients with a suspected bleeding disorder referred between January 2012 and March 2017 to an outpatient unit of a university hospital were prospectively collected. The diagnostic evaluation was performed according to current recommendations following a prespecified protocol and platelet function was tested using light transmission aggregometry as well as flow cytometry. RESULTS Five hundred and fifty-five patients were assessed; 66.9% were female, median age was 43.7 years (interquartile range [IQR] 29.3, 61.7). Confirmed platelet function disorder was diagnosed in 54 patients (9.7%), possible platelet function disorder in 64 patients (11.5%), and other disorders in 170 patients (30.6%). Median scoring of the ISTH-BAT was 2 in patients without a bleeding disorder (IQR 1, 3), 4 in patients with a possible platelet function disorder (2, 7), and 7 in patients with confirmed platelet function disorder (5, 9). Area under the receiver operating characteristic curve (the area under the curve [AUC]) was 0.75 (95% CI 0.70, 0.80). CONCLUSIONS Presence of a platelet function disorder was associated with substantially higher BAT scorings compared to patients without. Our data suggest that the ISTH-BAT provides a useful screening tool for patients with suspected platelet function disorders.
- Published
- 2019
45. Pregnancy with Chuvash Polycythaemia and Other Congenital Erythrocytosis
- Author
-
Julie Kaiser, Mathilde Gavillet, Lorenzo Alberio, Natacha Dewarrat, and David Baud
- Subjects
Adult ,medicine.medical_specialty ,Polycythaemia ,Iron ,Intrauterine growth restriction ,Polycythemia ,Chorioamnionitis ,Polymorphism, Single Nucleotide ,Miscarriage ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Humans ,Medicine ,Fetus ,Aspirin ,business.industry ,Obstetrics ,Homozygote ,Hematology ,General Medicine ,Heparin, Low-Molecular-Weight ,Phlebotomy ,medicine.disease ,Von Hippel-Lindau Tumor Suppressor Protein ,030220 oncology & carcinogenesis ,Ferritins ,Premature Birth ,Female ,business ,030215 immunology ,medicine.drug - Abstract
This original report describes the management of a pregnant woman with congenital erythrocytosis (Chuvash polycythaemia) and reviews the scarce data available in the literature. Therapy consisted of low-dose aspirin and phlebotomies to maintain haematocrit
- Published
- 2019
46. Kardiale Dekompensation, Arthralgien und generalisierter Pruritus
- Author
-
Francesco Grandoni, Lorenzo Alberio, Sabine Blum, Samuel Rotman, Mathilde Gavillet, and Gerasimos Tsilimidos
- Abstract
Ein 58-jahriger Patient sucht arztlichen Rat aufgrund einer Gewichtszunahme und progressiven Dyspnoe mit Beinodemen. Er beklagt zudem einen seit Monaten fortschreitenden Juckreiz sowie generalisierte Arthralgien.
- Published
- 2021
47. Décompensation cardiaque, arthralgies et prurit généralisé
- Author
-
Samuel Rotman, Gerasimos Tsilimidos, Mathilde Gavillet, Francesco Grandoni, Lorenzo Alberio, and Sabine Blum
- Abstract
Un patient de 58 ans consulte pour une prise ponderale et une dyspnee progressive avec des œdemes des membres inferieurs. Il rapporte un prurit evoluant depuis des mois ainsi que des arthralgies generalisees.
- Published
- 2021
48. Management of bleeding events and invasive procedures in patients with haemophilia A without inhibitors treated with emicizumab
- Author
-
Pierre, Fontana, Lorenzo, Alberio, Manuela, Albisetti, Anne, Angelillo-Scherrer, Lars M, Asmis, Alessandro, Casini, Bernhard, Gerber, Lukas, Graf, Inga, Hegemann, Wolfgang, Korte, Maria, Martinez, Jan-Dirk, Studt, Dimitrios A, Tsakiris, Walter A, Wuillemin, and Johanna A, Kremer Hovinga
- Subjects
Adult ,Antibodies, Bispecific ,Humans ,Hemorrhage ,Antibodies, Monoclonal, Humanized ,Child ,Hemophilia A - Abstract
Emicizumab (Hemlibrareg;, Hoffmann-La Roche, Switzerland) is now available for haemophilia A patients with or without factor VIII inhibitors. Management of bleeding events and replacement therapy for invasive procedures have to be adapted.To provide a practical guidance for the management of breakthrough bleeding events and elective or urgent surgery in adult and paediatric patients with haemophilia A without inhibitors treated with emicizumab.Based on the available literature and the experiences collected from adult and paediatric patients treated in Switzerland, the Working Party on Haemostasis of the Swiss Society of Haematology and the Swiss Haemophilia Network worked together to reach a consensus on the management of bleeding events and invasive procedures.Minor bleeding events and invasive procedures associated with low bleeding risk can be treated without factor replacement therapy in most cases, whereas major bleeding events and high-risk surgery require additional factor VIII replacement at usual doses, at least for the first days. Emicizumab treatment should be continued throughout the procedure and during the postoperative period. Elective major surgery should be planned according to emicizumab dosing for patients with a once-a-month posology. Of note, so far only few data are available on the management of major bleeds and surgery in patients with haemophilia A treated with emicizumab and this practical guidance will have to be regularly updated with growing experience.nbsp.
- Published
- 2020
49. Interprétation du dosage des anticorps anti-phospholipides
- Author
-
Camillo Ribi, Lorenzo Alberio, Raphael Burger, and Adnan Nozic
- Abstract
Une femme de 59 ans connue pour une hypertension arterielle traitee et un tabagisme actif est admise pour un episode de douleurs thoraciques six mois apres un triple pontage aorto-coronarien pour une maladie coronarienne severe.
- Published
- 2020
50. Emicizumab-Induced Seronegative Full-House Lupus Nephritis in a Child
- Author
-
Manuela Albisetti, Francois Cachat, Mattia Rizzi, Guy Young, Hassib Chehade, Maja Beck-Popovic, Lorenzo Alberio, Samuel Rotman, Léonore Diezi, University of Zurich, and Rizzi, Mattia
- Subjects
Male ,medicine.medical_specialty ,Lupus nephritis ,610 Medicine & health ,Antibodies, Monoclonal, Humanized ,Hemophilia A ,Pediatrics ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,030225 pediatrics ,Internal medicine ,Antibodies, Bispecific ,medicine ,Humans ,2735 Pediatrics, Perinatology and Child Health ,Child ,Adverse effect ,Emicizumab ,Factor VIII ,Proteinuria ,Leukopenia ,medicine.diagnostic_test ,business.industry ,medicine.disease ,Lupus Nephritis ,Perinatology ,and Child Health ,Coagulation ,10036 Medical Clinic ,Pediatrics, Perinatology and Child Health ,Renal biopsy ,medicine.symptom ,Complication ,business - Abstract
Hemophilia A (HA) is a serious inherited bleeding disorder resulting from a deficiency of coagulation factor VIII (FVIII). Replacement therapy with intravenous infusion of FVIII can be associated with treatment failure in approximately one-third of patients secondary to the development of neutralizing alloantibodies (inhibitor). Emicizumab is a recombinant, humanized, bispecific monoclonal antibody that binds factor IXa and factor X and mimics FVIII. It has been licensed in many countries for the treatment of patients with HA with and without inhibitors with a favorable efficacy and safety profile. A 7-year-old child with severe HA and FVIII inhibitors, refractory to immune tolerance therapy, developed hematuria with nephrotic-range proteinuria after the first dose of emicizumab and subsequently also after a second dose 6 weeks later, which was associated with mild and transient leukopenia. Renal biopsy revealed a pattern of a full-house lupus nephritis. The patient fully and spontaneously recovered between 2 weeks after symptoms onset. In this report, we provide insights on a new and so far unreported renal complication associated to emicizumab treatment. Although emicizumab offers significant benefits for patient with HA, clinicians should be aware of this rare and potential serious renal adverse effect.
- Published
- 2020
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