Emmanuel Favaloro

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

Objectives: There is limited information on the influence of collecting small amounts of blood on the quality of blood gas analysis. Therefore, the purpose of this study was to investigate the effects of different degrees of underfilling of syringes on test results of venous blood gas analysis. Methods: Venous blood was collected by venipuncture...

The use of artificial intelligence (AI) has become widespread in many areas of science and medicine, including laboratory medicine. Although it seems obvious that the analytical and post-analytical phases could be the most important fields of application in laboratory medicine, a kaleidoscope of new opportunities has emerged to extend the benefits...

Antiphospholipid syndrome (APS) is a hypercoagulable state caused by antiphospholipid antibodies (aPL). APS clinically manifests with arterial or venous or microvascular thrombi and/or pregnancy complications. It is well-known that the development of aPL can be a transient phenomenon and thus the current diagnostic criterion for APS requires repeat...

Objectives: Because there is little published evidence on the effects of incomplete filling of K2EDTA evacuated blood tubes on routine hematological testing, this original study aimed to provide updated information on this preanalytical aspect. Methods: The study population consisted of 17 ostensibly healthy volunteers. Blood was drawn by venipu...

This survey includes a series of questions about the nature, organization, and preparedness for emergencies, was created using Google forms, officially mailed to over 12,000 potential EFLM contacts with an official newsletter to collect responses between May 8 and June 8, 2023. Although obviously not representative of all European countries, the co...

Background: The EFLM Task Force Preparation of Labs for Emergencies (TF-PLE) created a survey that has been distributed to its members for gathering information on the key hazards experienced by European medical laboratories during the COVID-19 pandemic. Methods: The survey was distributed to over 12,000 potential contacts (laboratory workers) via...

Background. Because there is little published evidence on the effects of incomplete filling of K2EDTA evacuated blood tubes on routine hematological testing, this original study aimed to provide updated information on this preanalytical aspect. Materials and Methods. The study population consisted of 17 ostensibly healthy volunteers. Blood was draw...

This year's Congress of the International Society of Thrombosis and Haemostasis (ISTH) took place in person in Montréal, Canada, from June 24-28, 2023. The conference, held annually, highlighted cutting-edge advances in basic, translational, population and clinical sciences relevant to the Society. As for all ISTH congresses, we offered a special,...

von Willebrand disease (VWD) is considered the most common bleeding disorder and arises from deficiency and/or defect in the adhesive plasma protein von Willebrand factor (VWF). Diagnosis of VWD requires clinical assessment and is facilitated by laboratory testing. Several guidelines for VWD diagnosis exist, with the latest American Society of Hema...

Platelets are central elements of hemostasis and also play a pivotal role in the pathogenesis of thrombosis in coronavirus disease 2019. This study was planned to investigate the effects of different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recombinant spike protein variants on platelet morphology and activation. Citrated whole...

Long-coronavirus disease 2019 (COVID-19) represents a heterogeneous clinical syndrome characterized by a pathologic continuum of signs, symptoms, and also laboratory/radiologic abnormalities that may persist for a long time after recovering from an acute severe acute respiratory syndrome-coronavirus disease 2 infection. Among the various components...

There are typically three phases identified as contributing to the total testing process. The preanalytical phase starts with the clinician and the patient, when laboratory testing is being considered. This phase also includes decisions about which tests to order (or not), patient identification, blood collection, blood transport, sample processing...

Hemostasis laboratories play a crucial role in the diagnosis and treatment of individuals with bleeding or thrombotic disorders. Routine coagulation assays, including the prothrombin time (PT)/international normalized ratio (INR), and activated partial thromboplastin time (APTT), are used for various purposes. These include as a screen of hemostasi...

Thrombotic thrombocytopenic purpura (TTP) is a prothrombotic condition caused by a deficiency of ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). In turn, ADAMTS13 (also called von Willebrand factor (VWF) cleaving protease (VWFCP)) acts to cleave VWF multimers and thus reduce plasma VWF activity. In the...

Thrombotic thrombocytopenic purpura (TTP) is a prothrombotic condition caused by a significant deficiency of the enzyme, ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). In the absence of adequate levels of ADAMTS13 (i.e., in TTP), plasma VWF accumulates, in particular as "ultra-large" VWF multimers, and...

Heparin-induced thrombocytopenia (HIT) represents an autoimmune process whereby antibodies are formed against heparin in complex with platelet factor 4 (PF4) after heparin administration. These antibodies can be detected by a variety of immunological assays, including ELISA (enzyme-linked immunosorbent assay) and by chemiluminescence on the AcuStar...

Hemostasis is a complex but balanced process that permit normal blood flow, without adverse events. Disruption of the balance may lead to bleeding or thrombotic events, and clinical interventions may be required. Hemostasis laboratories typically offer an array of tests, including routine coagulation and specialized hemostasis assays used to guide...

Antiphospholipid (antibody) syndrome (APS) is a prothrombotic condition with increased risk for thrombosis and pregnancy-related morbidity. In addition to clinical criteria related to these risks, APS is characterized by the persistent presence of antiphospholipid antibodies (aPL), as detected in the laboratory using a potentially wide variety of a...

Activated protein C resistance (APCR) reflects a hemostatic state defined by a reduced ability of activated protein C (APC) to affect an anticoagulant response. This state of hemostatic imbalance is characterized by a heightened risk of venous thromboembolism. Protein C is an endogenous anticoagulant that is produced by the hepatocytes and undergoe...

Antiphospholipid antibodies (aPL) represent a group of autoantibodies directed against phospholipids. These antibodies may arise in a number of autoimmune conditions, of which the antiphospholipid (antibody) syndrome (APS) is best recognized. aPL can be detected by various laboratory assays, essentially comprising both solid-phase (immunological) a...

von Willebrand factor (VWF) is a large adhesive plasma protein that expresses several functional activities. One of these activities is to bind coagulation factor VIII (FVIII) and to protect it from degradation. Deficiency of, and/or defects in, VWF can give rise to a bleeding disorder called von Willebrand disease (VWD). The defect in VWF that aff...

von Willebrand disease (VWD) is the most commonly reported inherited bleeding disorder and may alternatively occur as an acquired von Willebrand syndrome (AVWS). VWD/AVWS develops from defects and/or deficiency in the adhesive plasma protein von Willebrand factor (VWF). VWD/AVWS diagnosis/exclusion remains challenging because of the heterogeneity o...

ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) is also called von Willebrand factor (VWF) cleaving protease (VWFCP). ADAMTS13 acts to cleave VWF multimers and thus reduce plasma VWF activity. In the absence of ADAMTS13 (i.e., in thrombotic thrombocytopenia purpura, TTP), plasma VWF can accumulate, in pa...

Harmonization and standardization of laboratory tests and procedures carry a variety of benefits. For example, within a laboratory network, harmonization/standardization provides a common platform for test procedures and documentation across different laboratories. This enables staff to be deployed across several laboratories, if required, without...

Introduction: Thrombotic thrombocytopenic purpura (TTP) is a rare but potentially fatal microangiopathy, with an untreated mortality rate of around 90%. TTP is caused by severe deficiency in ADAMTS13, which results in accumulation of ultra large von Willebrand factor multimers, triggering a consumptive thrombocytopenia, microangiopathic hemolytic...

Hemostasis can be defined as a homeostatic process in which the body attempts to minimize loss of blood by balancing out pro- and anti-procoagulant forces [...]

Background: Anti-platelet factor 4 (PF4) antibodies in vaccine-induced immune thrombotic thrombocytopenia (VITT) appear to be transient, with discrepant persistence depending on the platform used for detection. Objectives: We aimed to report a longitudinal study of antibody persistence using 2 ELISA platforms and 2 platelet-activating functional...

The von Willebrand factor (VWF) collagen binding (VWF:CB) assay was first reported for use in von Willebrand diagnostics in 1986, by Brown and Bosak. Since then, the VWF:CB has continued to be used to help diagnose von Willebrand disease (VWD) (correctly) and also to help assign the correct subtype, as well as to assist in the monitoring of VWD the...

Welcome to the latest issue of Seminars in Thrombosis and Hemostasis (STH) published under the “banner” of “Editorial Compilation,” with this being the thirteenth such issue. Although Seminars in Thrombosis and Hemostasis is historically a theme-driven publication, ongoing opportunities emerge to disseminate wide-ranging contributions of current in...

There is no certainty in change, other than change is certain. As Seminars in Thrombosis and Hemostasis celebrates 50 years of publication, I felt it appropriate to reflect on my own 40-year plus scientific career. My career in the thrombosis and hemostasis field did not start until 1987, but the subsequent 35 years reflected a period of significan...

Heparin-induced thrombocytopenia (HIT) and vaccine-induced immune thrombotic thrombocytopenia (VITT) are rare, iatrogenic immune-mediated conditions with high rates of thrombosis-related morbidity and mortality. HIT is a long-recognized reaction to the administration of the common parenterally administered anticoagulant heparin (or its derivatives)...

Introduction: : Unfractionated heparin remains the most widely used agent in the prevention and acute treatment of thrombosis. Pharmacological complexities of this intriguing agent mandate frequent monitoring of its anticoagulant properties to maintain safe and effective hematological outcome. Although activated partial thromboplastin time has bee...

Welcome to another issue of Seminars in Thrombosis and Hemostasis (STH), published under the “banner” of “Maintaining hemostasis and preventing thrombosis in coronavirus disease 2019 (COVID-19),” this being Part IV, or the fourth such volume. The first three issues were, respectively, published in 2020, 2021, and 2022, and proved very popular with...

Hemostasis reflects a homeostatic mechanism that aims to balance out pro-coagulant and anti-coagulant forces to maintain blood flow within the circulation. Simplistically, a relative excess of procoagulant forces can lead to thrombosis, and a relative excess of anticoagulant forces can lead to bleeding. There are a wide variety of congenital disord...

Parenteral anticoagulants are a class of anticoagulants that need to be administered non-orally, usually by injection or infusion. There are a variety of such agents, but heparin reflects the most frequently used. Being alerted to an error in a prior publication in which the word 'parenteral' was inadvertently replaced by the word 'parental', it be...

For more than a decade, US laboratories have failed to implement solutions to help their clinicians in managing complex situations or patients on DOACs. The problem may find different origins among which the position of the Food and Drug Administration, which categorized these drugs as monitoring‐ and measurement‐free, while other regulatory bodies...

We aim to provide here an update with infodemiological data reflecting the global volume of Web searches for anticoagulant medications during the past 10 years, which is now known to reliably mirror their real-world usage. The results of our infodemiological analysis suggest that apixaban seems to be the most searched anticoagulant drugs all around...

von Willebrand disease (VWD) is reportedly the most common inherited bleeding disorder, and can also arise as an acquired (von Willebrand) syndrome (AVWS). The hemostasis laboratory plays a key role in the diagnosis or exclusion of VWD/AVWS, which may otherwise be suspected due to the patient's clinical (bleeding) history. VWD/AVWS arise from defic...

Background: VITT is a rare complication of adenovirus-based vaccines aimed to prevent and minimise COVID-19 and related pathophysiology. Objectives: To describe patterns of testing for anti-platelet factor 4 (PF4) antibodies using various ELISA assays in a large Australian cohort and comparative functional platelet activation assays in a subset....

The evidence emerged so far would hence persuade us that, perhaps, the most reasonable approach is not a matter of whether therapeutic-intensity anticoagulation may be “good” or “bad,” “safe,” or “dangerous,” in patients with severe COVID-19 illness, but rather whether the correct answer to the original question could be… “depends.” Straightforward...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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)...

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...

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...

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...

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...

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...

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 relevant...

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...

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...

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...

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...

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...

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...

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...