Pr Lorenzo Alberio

Spécialisations

• Hématologie clinique (FMH) et de laboratoire (FAMH)
• Médecine interne (FMH)

Domaines d'intérêts académique et/ou clinique

• Hématologie générale, hémostase et thrombose, 
• Techniques de laboratoire hémostase et thrombose, cytométrie de flux

Education et formation

• Professeur associé UNIL : 2014
• Professeur associé UNIBE : 2009
• Venia docendi UNIBE : 2004
• FAMH hématologie (incl. analyses ADN/ARN) : 2002
• FMH hématologie : 1999
• FMH médecine interne : 1996
• Doctorat en médecine : 1993
• Diplôme de médecine : 1990

Institutions de formation et expériences précédentes

• Université de Berne, Faculté de médecine
• Ente Ospedaliero Cantonale, Ticino
• Inselspital, Hôpital universitaire, Berne
• University of Oklahoma, Health Sciences Center, Oklahoma City, USA
• Université de Strasbourg, UMR S949 INSERM, Établissement Français du Sang, Strasbourg, F

Langues parlées

• Français, Anglais, Allemand, Italien,

Procoagulant COAT platelets

At sites of vascular injury, platelets become exposed to collagen and thrombin, the strongest physiologic platelet agonists. We have described and characterized a fraction of platelets that, upon combined activation by collagen and thrombin, become highly efficient in sustaining thrombin generation and coagulation (Blood 2000;95:1694). Procoagulant collagen-and-thrombin (COAT) activated platelets express negatively charged aminophospholipids, loose their aggregation properties, and retain a coat of procoagulant and prohemostatic α-granules proteins on their surface, e.g. factor V, fibrinogen, VWF, thrombospondin, fibronectin, and α2-antiplasmin, in a serotonin- and transglutaminase-dependent manner (Nature 2002;415:175). Recent work of our group has shown that:

1. A diminished ability to generate COAT platelets leads to a clinically relevant bleeding diathesis (Cytometry Part B Clin Cytom 2014;86:397). This novel observation highlights the physiological relevance of platelet procoagulant activity besides aggregation.
2. The in vivo administration of DDAVP (desmopressin) selectively enhances COAT platelet generation (Blood 2014;123:1905). This is a novel mechanism explaining the beneficial hemostatic action of DDAVP in platelet disorders.
3. Intracellular signaling strikingly diverges starting about two minutes after platelet activation by collagen and thrombin (Thromb Haemost. 2017; 117:1101).

Our current interests are:

• To further dissect signaling mechanisms underlying and modulating COAT platelet generation such as dichotomous ion fluxes and protein phosphorylation.
• To study the role and clinical impact of COAT platelets in hematological diseases, such as paroxysmal nocturnal hemoglobinuria (PNH), myeloproliferative neoplasms (MPN), and heparin-induced thrombocytopenia (HIT).
• To study the role of COAT platelets in transfusion medicine. This work is performed in in collaboration with the “Laboratoire de Recherche sur les Produits Sanguins” of the  “Transfusion Interrégionale Croix Rouge Suisse SA” in Epalinges.

Thrombin generation

Thrombin generation  assays  are “global assays” that have the capacity to give an overall evaluation of the coagulation potential. We are currently evaluating their diagnostic utility in following clinical conditions:

• Rare bleeding disorders, such as FXI deficiency (in which the risk of bleeding is not easily predictable since it does not correlate with measured FXI levels) and haemophilia (in which monitoring of enhanced half-life factor FVIII and FIX concentrates remain a challenge).
• The new direct oral anticoagulants (DOAC). We have recently observed in obese patients that the ex vivo anticoagulant action of Rivaroxaban (RVX) measured by thrombin generation (TG) does not predict the in vivo anticoagulant effect (Int J Lab Hematol 2018;40:e11). Our current interest is to assess the anticoagulant effect of similar plasma concentrations of RVX in different subjects and in the same subject before and after surgery. This project is a collaboration with the  Department of Visceral Surgery and Medicine of the Inselpital Bern.
• Patients with liver disease, in order to detect hypercoagulability. This project is a collaboration with the Division of Gastroenterology and Hepatology of the CHUV.

Heparin-induced thrombocytopenia (HIT)

HIT represents a fascinating hemostatic paradox (thrombocytopenic anticoagulated patients develop a life-threatening prothrombotic state) and a challenging clinical problem. Over the years our group has investigated mechanistic, diagnostic, and therapeutic aspects of HIT (Thromb Haemost 2004;91:276; JTH 2009;7:1649; Blood 2009;113:2402). In particular, we have developed a Bayesian diagnostic approach in order to reach a rapid exclusion or confirmation of suspected HIT (Haematologica 2012;97:89).

Our current interests are:

• The validation of a rapid and accurate diagnostic algorithm for HIT diagnosis.
• The dissection of platelet intracellular signaling events induced by anti-PF4/heparin-antibodies, specifically their ability to generate procoagulant COAT platelets.
• The ability of anti-platelet drugs to prevent anti-PF4/heparin antibody induced platelet aggregation. This project is a collaboration with the Department of Anesthesiology of the CHUV.

• Debora Bertaggia Calderara
  Biologist, PhD, Chargée de recherche

Debora Bertaggia Calderara obtained her Master in biological sciences from the University of Padova (1994), Italy and a PhD Degree in molecular biology from the University of Pisa (1999), Italy. During her PhD, she worked at the University of Camerino, Italy and at the Swiss Federal Institute of Zurich, where she gained extensive experience as a molecular biologist. Her thesis focused on the cloning and study of the expression of metallothionein proteins, which protect organisms from metal toxicity and oxidative stress. Wishing to improve her knowledge in genetics, she worked (1999-2001) as a postdoc Fellow in the laboratory of Pr Craig Montell (Department of biological chemistry) at the Johns Hopkins University, School of Medicine in Baltimore, USA, studying receptor and ion channels that control behavior in the fruitfly Drosophila melanogaster. In May 2003, she joined the diagnostic laboratory of molecular biology (Hematology Section) at the CHUV. From 2004 to 2011 she worked in the research group of Pr O. Spertini, studying the biology of leukemia cells and the role of adhesion receptors. After parental leave (2011 to 2013), in  April 2014 she joined the research group of Pr Alberio and became deeply  interested in hemostasis research. Her work focus on the role of COAT platelets in transfusion medicine and in studying the clinical utility of global hemostasis tests measuring thrombin generation, in patients taking new oral anticoagulant (DOACs) and in patients with rare bleeding disorders

• Alessandro Aliotta
  Ingénieur EPFL, PhD Student

Alessandro Aliotta graduated from the Ecole polytechnique fédérale de Lausanne (EPFL) in 2016 as an Engineer in Life Sciences and Technologies (MSc) with a specialization in Molecular Medicine. He worked as research assistant in the blood products research laboratory at Inter-regional blood transfusion SRC, on research projects related to blood platelet concentrate storage lesions and pathogen inactivation procedure impact (2013-2014). His master's project was undertaken at the University hospitals of Geneva in the translational biomarker group, working on blood-circulating microvesicles for the research of early toxicity biomarkers in patients that encountered paracetamol liver toxicity (2015-2016). In November 2016, Alessandro joined the research group of Pr Alberio to perform his PhD studies. He is interested in the processes involved in platelet procoagulant activity and their clinical impact. His project focusses on developing flow cytometric methods to investigate intracellular signaling pathways and mechanisms underlying formation of procoagulant COAT platelets.

• Matteo Marchetti

Matteo Marchetti finished medical school 2018. He studied in Lausanne (Université de Lausanne, Faculté de Biologie et Médecine) and Heidelberg (UniversitätsKlinikum, Medizinische Fakultät Heidelberg). He is interested in developing an efficient and evidence-based approach for the diagnosis and management of heparin-induced thrombocytopenia (HIT). His Master's project was undertaken at the University Hospital of Lausanne (CHUV) in the haemostasis research group of Pr Alberio. Since 2015, he has been working on developing a new rapid and diagnostic approach of HIT that is based on approximately 1,000 patients with HIT suspicion (2014-2019). He is currently working on his thesis project, which deals with the treatment of HIT with alternative anticoagulants..

• Maxime Zermatten

Maxime Zermatten obtained his bachelor's in human medicine from the University of Fribourg (CH) in 2012 before going on to obtain his master's and his federal diploma in human medicine from the University of Bern, in 2015. His master's thesis and his MD (ongoing) were undertaken at the University of Bern's Department of pediatrics, in pediatric oncology and hematology, working on risk prediction of fever in neutropenia in children with cancer. He completed his first clinical experience as an internal medicine resident at the Hôpital Fribourgeois (HFR) of Tafers (2015-2016 and 2017-2018) and in pediatrics in the Department of pediatrics, at the University Hospital of Bern (2016-2017). Maxime decided to explore new horizons and broaden his competence in hematology and laboratory research by joining the research group of Pr Alberio in October 2018. 

• Manuel Krüsi

Prior to his medical studies, Manuel Krüsi obtained an advanced federal diploma of higher education as a registered biomedical scientist. In his third year of medical school (University of Lausanne), he started working part-time in several medical laboratories and is currently employed in the Service of hematology of the University Hospital of Zürich.  Currently (2019) on the point of starting his fifth year of medical school, in the context of his master's thesis, Manuel Krüsi is assisting Alessandro Aliotta in his research.