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Emmanuel Favaloro

Emmanuel Favaloro
NSW Health Pathology, ICPMR, Westmead Hospital · Haematology, Sydney Centres for Thrombosis and Haemostasis

BSc (Hons), PhD, FFSc (RCPA)

About

799
Publications
208,764
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22,472
Citations
Additional affiliations
January 1981 - present
Westmead Hospital
Position
  • Principal Hospital Scientist

Publications

Publications (799)
Article
Coagulation factor testing is commonly performed within haemostasis laboratories, either to assess for bleeding disorders, such as haemophilia, or to investigate unexplained prolongation in routine coagulation assays. The aim of this evaluation was to harmonize procedures and normal reference ranges (NRRs) for investigation of coagulation factors o...
Article
Full-text available
The platelet function analyser (PFA) is a prevalent platelet function screening instrument, and comes in two models–the original PFA-100 and the contemporary PFA-200. The instruments have ‘identical’ output, being a ‘closure time’ (CT). Moreover, normal reference ranges provided by the manufacturer, for the specific test cartridges, are the same fo...
Article
Full-text available
D-dimers reflect a breakdown product of fibrin. The current narrative review outlines how D-dimers can arise in normal individuals, as well as in patients suffering from a wide range of disease states. D-dimers in normal individuals without evident thrombosis can arise from background fibrinolytic activity in various tissues, including kidney, mamm...
Article
von Willebrand factor (VWF) forms high-molecular-weight multimers and plays an essential role in hemostasis, and thus its deficiency leads to bleeding symptoms. Acquired von Willebrand syndrome (AVWS) is rare, but potentially underdiagnosed, and develops in various underlying disorders. AVWS caused by anti-VWF autoantibodies is a rare subcategory o...
Article
von Willebrand disease (VWD) is a common bleeding disorder that arises from deficiency and/or defects of von Willebrand factor (VWF). Appropriate diagnosis of VWD, including differential identification of qualitative (types 2A, 2B, 2M, 2N VWD) versus quantitative (types 1 and 3 VWD) defects remains problematic but has important management implicati...
Article
Full-text available
D-dimer is a fibrin degradation product encompassing multiple cross-linked D domains and/or E domains present in the original fibrinogen molecule, whose generation is only theoretically possible when hemostasis and fibrinolysis pathways are concomitantly activated. D-dimer measurement has now become a pillar in the diagnosis/exclusion and prognosti...
Article
Welcome to the latest issue of Seminars in Thrombosis and Hemostasis (STH) published under the “banner” of “Editorial Compilation,” this being the twelfth such issue. Although Seminars in Thrombosis and Hemostasis is historically a theme-driven publication, ongoing opportunities emerge to disseminate wide-ranging contributions of current interest o...
Article
Introduction: The platelet function analyzer (PFA) is a popular platelet function screening instrument, highly sensitive to von Willebrand disease (VWD) and to aspirin therapy, with moderate sensitivity to defects in platelet function and/or deficiencies in platelet number. There are two models, the original PFA-100 and the contemporary PFA-200. N...
Article
Although the worldwide usage of direct oral anticoagulants has continuously increate over the past decade, heparin remains an important weapon in the current arsenal of anticoagulant drugs. Parenteral heparin administration (i.e., either intravenously or subcutaneously) has represented for decades the only possible route for generating a significan...
Article
COVID-19 is now established to be associated with a thrombotic phenomenon, now called COVID-19 associated coagulopathy (CAC). Anti-Endothelial Cell Antibodies (AECA) are a heterogenous group of autoantibodies targeting various endothelial cell antigens or antigens adhering to endothelial cells, They are commonly observed in a variety of auto-immune...
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Background Dysregulation of complement system is thought to be a major player in development of multi-organ damage and adverse outcomes in patients with coronavirus disease 2019 (COVID-19). This study aimed to examine associations between complement system activity and development of severe acute kidney injury (AKI) among hospitalized COVID-19 pati...
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Introduction: Neutrophil extracellular traps (NETs) release (i.e., NETosis) has been recently implicated in the pathomechanism underlying severe end-organ damage in Coronavirus Disease 2019 (COVID-19) and could present a novel therapeutic target. We aimed to determine whether circulating levels of cell-free DNA (cfDNA), a surrogate for NETosis, may...
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Full-text available
Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe prothrombotic complication of adenoviral vaccines, including ChAdOx1 nCoV-19 (Vaxzevria) vaccine. The putative mechanism involves formation of pathological anti-PF4 antibodies that activate platelets via the FcγRIIa receptor to drive thrombosis and thrombocytopenia. Functional as...
Article
Full-text available
COVID-19 is now established to be associated with a thrombotic phenomenon, now called COVID-19 associated coagulopathy (CAC). Anti-Endothelial Cell Antibodies (AECA) are a heterogenous group of autoantibodies targeting various endothelial cell antigens or antigens adhering to endothelial cells, They are commonly observed in a variety of auto-immune...
Article
Contrary to the inherent meaning of the term, smartphones are no longer devices used for only making phone calls, as their usage is now widespread for hundreds (thousands?) of other reasons. Smartphones are probably the devices that we use most frequently in our day-to-day lives. Smartphones are always with us, and they hence represent the most pra...
Article
Full-text available
von Willebrand factor (VWF) is a complex and large protein that is cleaved by ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13), and together they serve important roles in normal hemostasis. Malignancy can result in both a deficiency or excess of VWF, leading to aberrant hemostasis with either increased blee...
Article
Welcome to the latest issue of Seminars in Thrombosis and Hemostasis (STH) published under the “banner” of “Editorial Compilation,” this being the 11th such issue. Although Seminars in Thrombosis and Hemostasis is historically a theme-driven publication, ongoing opportunities emerge to disseminate wide-ranging contributions of current interest or c...
Article
Full-text available
Introduction: Lupus anticoagulant (LA) testing is commonly performed within hemostasis laboratories, and the ACL TOP 50 family of instruments represent a new "single platform" of hemostasis instrumentation. Our aim was to evaluate these instruments and manufacturer reagents or alternatives for utility in LA testing. Methods: Comparative evaluati...
Article
Objectives To advance knowledge in using the ex vivo method to identify factor sensitivity of the activated partial thromboplastin time (APTT), using data from a hemophilia and reference hemostasis laboratory; to evaluate application of inclusion and exclusion criteria to eliminate data outliers; and to discuss outcomes with reference to comparable...
Article
Platelet factor 4 (PF4), a protein stored in the alpha-granules of platelets and released upon activation, forms cationic tetramers that bind with various polymeric anions, including heparin. Some individuals develop antibodies against PF4 in complex with heparin (PF4/H), which potentially lead to the onset of heparin induced thrombocytopenia (HIT)...
Article
Welcome to another issue of Seminars in Thrombosis and Hemostasis (STH). This issue is published under the “continuing banner” of “Maintaining hemostasis and preventing thrombosis in coronavirus disease 2019 (COVID-19),” this being Part III, or the third such issue. The first two issues were respectively published in 2020 and 2021 and proved very p...
Article
Full-text available
Laboratory assessment of blood coagulation factors may be undertaken for various reasons, including investigating the possibility of hemophilia or unexpected prolongation in routine coagulation assays (eg, prothrombin time, activated partial thromboplastin time). Several guidelines recommend performing multiple dilutions (usually 2‐3) on all patien...
Article
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Background: Lupus anticoagulants (LA) are one laboratory criterion for classification of antiphospholipid syndrome, with presence of vascular thrombosis and/or pregnancy/fetal morbidity being clinical criteria. The presence of LA is detected (or excluded) by laboratory testing, with the activated partial thromboplastin time and dilute Russell's vi...
Article
The consolidated evidence that SARS-CoV-2 is efficiently able to interplay with heparan sulfate proteoglycans on host cell surface for primary attachment before high-affinity interaction of RBD with ACE2, provides reasonable and reinforced support for the importance of heparin usage in COVID-19. In fact, the antiviral activity of heparin may ultima...
Article
Full-text available
Antibodies against platelet factor 4 (PF4), a protein released from alpha-granules of activated platelets, may cause a number of pathophysiological conditions. The most commonly known is heparin-induced thrombocytopenia (HIT), which develops in a small proportion of people treated with the anticoagulant drug heparin. Notably, PF4 binds with high af...
Article
Full-text available
Background: Heparin-induced thrombocytopenia (HIT) is a prothrombotic, immune-mediated adverse drug reaction associated with high rates of thrombosis-related morbidity and mortality caused by FcγRIIa-activating pathogenic antibodies to PF4-heparin. Procoagulant platelets are a platelet subset that promote thrombin generation, are clinically releva...
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Full-text available
Coagulopathy is a key feature of COVID-19 and D-dimer has been reported as a predictor of severity. However, because D-dimer test results vary considerably among assays, resolving harmonization issues is fundamental to translate findings into clinical practice. In this retrospective multicenter study (BIOCOVID study), we aimed to analyze the value...
Article
The clinical course of coronavirus disease 2019 (COVID-19) is often complicated by the onset of venous thrombosis and thromboembolism (VTE), encompassing also pulmonary thrombosis. Recent statistics attests that the cumulative frequency of VTE can be as high as 30% in COVID-19 hospitalized patients, increasing to nearly 40 to 70% (depending on syst...
Article
Full-text available
The recent American Society of Hematology/ISTH/National Hemophilia Foundation/World Federation of Hemophilia 2021 guidelines on the diagnosis of von Willebrand disease (VWD) is an outstanding effort to unify the diagnosis of VWD. However, as mentioned in the guidelines, there are limitations due to the low certainty in the evidence identified for m...
Article
Introduction The CHaDOx1 nCov-19 AstraZeneca (AZ) vaccination has been associated with an antibody-mediated prothrombotic syndrome, termed "Thrombosis with Thrombocytopenia Syndrome" (TTS)[1-3]. The current diagnostic criteria for TTS are thrombosis (venous or arterial) within 4-42 days of AZ vaccine, thrombocytopenia and presence of an antibody to...
Article
Background: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe prothrombotic complication of adenoviral vaccines including ChAdOx1 nCoV-19 (AstraZeneca) vaccine. The putative mechanism involves formation of pathological anti-PF4 antibodies that activate platelets via the FcγRIIa receptor to drive thrombosis and the associated thr...
Article
Lipoprotein(a) (Lp(a)) is a prothrombotic and anti-fibrinolytic lipoprotein, whose role has not been clearly defined in the pathogenesis of coronavirus disease 2019 (COVID-19). In this prospective observational study, serum Lp(a) as well as outcomes were measured in 50 COVID-19 patients and 30 matched sick controls. Lp(a) was also assessed for corr...
Article
Coronavirus disease 2019 (COVID-19) is a life threatening infectious disease caused by Severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2). In response to the still ongoing pandemic outbreak, a number of COVID-19 vaccines have been quickly developed and deployed. Although minor adverse events, either local (e.g., soreness, itch, redness) o...
Article
Welcome to the latest issue of Seminars in Thrombosis and Hemostasis (STH) published under the “banner” of “Editorial Compilation,” this being the tenth such issue. Although STH is historically a theme-driven publication, ongoing opportunities arise to publish compilations containing wide-ranging contributions of current interest and controversy, a...
Article
Full-text available
von Willebrand factor (VWF) is an adhesive protein involved in primary hemostasis and facilitates platelet adhesion to sites of vascular injury, thereby promoting thrombus formation. VWF exists in plasma as multimers of increasing size, with the largest (high molecular weight; HMW) expressing the greatest functional activity. A deficiency of VWF is...
Article
Despite the huge efforts globally underway for preventing or limiting the spread of severe acute respiratory coronavirus disease 2 (SARS-CoV-2), the coronavirus disease 2019 (COVID-19) pandemic outbreak appears still virtually unstoppable. As for many other infectious diseases, COVID-19 vaccination has now become crucial for limiting viral spread,...
Article
von Willebrand disease (VWD) arises from deficiency and/or defects of von Willebrand factor (VWF). Assessment requires test panels, including VWF activity and antigen. Appropriate diagnosis including differential identification of qualitative versus quantitative defects remains problematic but has important management implications. Data using a lar...
Article
Full-text available
Recent manufacturing problems and increased utilization has created a shortage of 3.2% sodium citrate blood collection tubes used for coagulation testing, causing stakeholders such as hospitals, clinics and laboratories, to find suitable alternatives. Considerations for in-house citrate blood collection tube preparations or purchasing commercial pr...
Article
Full-text available
ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), also known as VWF (von Willebrand factor) protease, may be assessed in a vast array of clinical conditions. Notably, a severe deficiency of ADAMTS13 characterises TTP (thrombotic thrombocytopenic purpura), a rare but potentially fatal disorder associated w...
Article
Full-text available
Despite von Willebrand disease (VWD) being the most common inherited bleeding disorder, its accurate diagnosis is frequently shrouded by diagnostic pitfalls. VWD is frequently under-diagnosed, over-diagnosed and misdiagnosed, leading to significant avoidable patient morbidity and health care system burden. At the heart of this dilemma lies the hete...
Article
Full-text available
von Willebrand factor (VWF) is a large, adhesive, multimeric protein involved in haemostasis. The larger the size (or number of VWF multimers), the greater the functionality of the protein. A deficiency or defect in VWF can lead to von Willebrand disease (VWD) and cause bleeding, whereas an increase in VWF may cause thrombosis. ADAMTS13 (a disinteg...
Article
Keywords ► disease-causing variants ► phenotype-genotype ► von Willebrand disease ► von Willebrand factor ► collagen binding Abstract Type 2A and 2M von Willebrand disease (VWD) broadly show similar phenotypic parameters, but involve different pathophysiological mechanisms. This report presents the clinical and laboratory profiles of type 2A and ty...
Article
The term “lupus anticoagulant (LA)” identifies a form of antiphospholipid antibodies (aPLs) causing prolongation of clotting tests in a phospholipid concentration-dependent manner. LA is one of the laboratory criteria identified in patients with antiphospholipid (antibody) syndrome (APS). The presence of LA in patients with APS represents a signifi...
Article
Antiphospholipid antibodies (aPL) comprise a panel of autoantibodies that reflect a potential prothrombotic risk in several autoimmune conditions, most notably antiphospholipid (antibody) syndrome (APS). aPL can be divided into those that form part of the laboratory criteria for APS, namely, lupus anticoagulant (LA), as well as anticardiolipin anti...
Article
Objectives: Thrombophilia testing is commonly performed within hemostasis laboratories, and the ACL TOP 50 family of instruments represent a new 'single platform' of hemostasis instrumentation. The study objective was to evaluate these instruments and manufacturer reagents for utility of congenital thrombophilia assays. Methods: Comparative eval...
Article
Full-text available
Since renal injury, and various forms of venous thrombosis, are commonplace in patients with severe coronavirus disease 2019 (COVID-19), we aimed to review scientific studies which explored the concentration of suPAR in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with or without critical illness. Five studie...
Article
COVID-19 is largely a vascular disease, and that severe COVID-19 manifests with thrombosis in around one-third of affected patients, and even more in those needing mechanical ventilation and/or intensive care. Notably, all the three essential elements that compose the Virchow's triad can be found in COVID-19.
Article
COVID‐19 (coronavirus disease 2019) represents a pandemic, and several vaccines have been produced to prevent infection and/or severe sequelae associated with SARS‐CoV‐2 (severe acute respiratory syndrome coronavirus 2) infection. There have been several reports of infrequent post vaccine associated thrombotic events, in particular for adenovirus‐b...
Article
COVID‐19 (coronavirus disease 2019) represents a prothrombotic disorder, and there have been several reports of platelet factor 4/heparin antibodies being present in COVID‐19‐infected patients. This has thus been identified in some publications as representing a high incidence of heparin‐induced thrombocytopenia (HIT), whereas in others, findings h...
Article
von Willebrand factor (VWF) is a large adhesive multimeric protein involved in hemostasis. The larger the size (or number of VWF multimers), the greater the functionality of the protein. A deficiency or defect of VWF can lead to von Willebrand disease (VWD) and cause bleeding. Conversely, an increase in VWF may create an environment that promotes t...
Article
Objectives: To verify a single platform of hemostasis instrumentation, the ACL TOP 50 Family, comprising 350, 550, and 750 instruments, across a large network of 60 laboratories. Methods: Comparative evaluations of instrument classes (350 vs 550 and 750) were performed using a large battery of test samples for routine coagulation tests, comprisi...
Article
Since coronavirus disease 2019 (COVID-19), a life-threatening infectious disease sustained by the severe respiratory syndrome coronavirus 2 (SARS-CoV-2), is frequently complicated by thrombotic episodes, both venous and arterial, we provide here an updated analysis of current scientific literature data exploring the association between mean platele...
Article
Full-text available
In 2018, the International Council for Standardization in Hematology (ICSH) published a consensus document providing guidance for laboratories on measuring direct oral anticoagulants (DOACs). Since that publication, several significant changes related to DOACs have occurred, including the approval of a new DOAC by the Food and Drug Administration,...
Article
Introduction: Immune-mediated heparin-induced thrombocytopenia (HIT) is an infrequent complication following heparin exposure but with a potentially fatal outcome due to thrombotic complications. Prompt suspension of heparin is necessary if HIT is suspected, followed by initiation of non-heparin anticoagulant therapy. Areas covered: In this review,...
Article
Full-text available
“The Only Constant in Life Is Change.” – Heraclitus Change has been a continuum in the field of hemostasis since the field began. The elder of us has personal recollections of starting in the field performing manual coagulation tests. He thought the workload was high, performing up to 40 prothrombin times (PTs) and activated partial thromboplastin...
Article
Type 2B von Willebrand disease (2B VWD) is a rare, autosomal dominant bleeding disorder characterized by a hyperadhesive form of von Willebrand factor (VWF). 2B VWD expresses phenotypically as an enhanced ristocetin-induced platelet aggregation and usually also a discordance in VWF activity versus protein level, with loss of high molecular weight V...
Article
In conclusion, patients with severe COVID-19 have significantly elevated plasma levels of PAI-1. Elevated levels of tPA and PAI-1 are independent predictors of progression to severe COVID-19. The evidence provided suggests that fibrinolytics should continue to be investigated as therapeutic avenue in patients with COVID-19.
Article
Full-text available
Introduction. Severe COVID‐19 is often compounded by a prothrombotic state that is associated with poor outcomes. In this investigation, we aimed to evaluate ADAMTS13 activity, von Willebrand factor level (VWF:Ag), and the corresponding ADAMTS13 activity/VWF:Ag ratio, in patients with COVID‐19 and for associations with disease progression and acute...
Article
This guidance focuses on methodological aspects of lupus anticoagulant (LA) testing, as well as interpretation of results for clinicians. The main changes in how to test for LA compared with the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee 2009 guidelines, in the preanalytical phase are more detailed...
Article
Introduction: von Willebrand disease (VWD) is the most common inherited bleeding disorder and caused by an absence, deficiency or defect in von Willebrand factor (VWF). VWD is currently classified into six different types: 1, 2A, 2B, 2N, 2M, 3. Notably, 2M VWD is more often misdiagnosed as 2A or type 1 VWD than properly identified as 2M VWD. Aim:...
Article
Patients with the severe form of coronavirus disease 2019 (COVID-19) have been frequently found to suffer from both arterial and venous thrombotic events due to the perpetuation of a hypercoagulable state. This phenomenon, termed COVID-19-associated coagulopathy (CC), is now considered a major component of the pathophysiology of this novel infectio...
Article
Although further evidence, based on solid cost-effectiveness analyses, would be needed to make definitive conclusions on this matter, it is undeniable that routine D-dimer measurement may currently help identifying a subset of COVID-19 patients at enhanced risk of unfavorable progression, who may then benefit from more extensive assessment and tail...
Article
Heparin induced thrombocytopenia (HIT) is a rare but potentially fatal complication of heparin therapy. In some patients, HIT causes platelet activation and thrombosis (sometimes abbreviated HITT), which leads to adverse clinical sequalae ('pathological HIT'). The likelihood of HIT is initially assessed clinically, typically using a scoring system,...
Article
Background Thrombotic thrombocytopenic purpura (TTP) is a rare but potentially fatal disorder caused by ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) deficiency. Prompt identification/exclusion of TTP can thus be facilitated by rapid ADAMTS13 testing. The most commonly utilized (enzyme‐linked immunosor...
Article
Full-text available
The prothrombin time (PT) represents the most commonly used coagulation test in clinical laboratories. The PT is mathematically converted to the international normalized ratio (INR) for use in monitoring anticoagulant therapy with vitamin K antagonists such as warfarin in order to provide test results that are adjusted for thromboplastin and instru...
Article
Beyond several well-established venous thromboembolism VTE risk factors, venous thrombosis may also be triggered by unusual and unsuspected conditions. The current scientific evidence—although limited both in time and quantity—would support the existence of a causal relationship between periodontal disease (especially severe) and VTE. In our analys...
Article
In conclusion, we observed that patients with COVID-19 present to the ED with normal levels of plasminogen, but those progressing to severe disease demonstrate mildly lower values suggestive of consumption for fibrinolysis activation. Future studies aimed at investigating the pathophysiology of CAC should include serial measurements of multiple com...