Abstract
In late December 2019 an outbreak of a novel coronavirus (SARS-CoV-2) causing severe pneumonia (COVID-19) was reported in Wuhan, Hubei Province, China. A common finding in most COVID-19 ...patients is high D-dimer levels which are associated with a worse prognosis. We aimed to evaluate coagulation abnormalities via traditional tests and whole blood thromboelastometry profiles in a group of 22 (mean age 67 ± 8 years, M:F 20:2) consecutive patients admitted to the Intensive Care Unit of Padova University Hospital for acute respiratory failure due to COVID-19. Cases showed significantly higher fibrinogen and D-dimer plasma levels versus healthy controls (
p
< 0.0001 in both comparisons). Interestingly enough, markedly hypercoagulable thromboelastometry profiles were observed in COVID-19 patients, as reflected by shorter Clot Formation Time (CFT) in INTEM (
p
= 0.0002) and EXTEM (
p
= 0.01) and higher Maximum Clot Firmness (MCF) in INTEM, EXTEM and FIBTEM (
p
< 0.001 in all comparisons). In conclusion, COVID-19 patients with acute respiratory failure present a severe hypercoagulability rather than consumptive coagulopathy. Fibrin formation and polymerization may predispose to thrombosis and correlate with a worse outcome.
Hemorrhage is defined as an acute loss of blood from the cardiovascular system. The hemostatic cascade (comprising the vasculature, coagulation factors, the fibrinolytic and the platelet systems) is ...the physiological mechanism meant to control this event. Coagulation assessment is fundamental in the monitoring and treatment of hemorrhage. Over the years several classical laboratory-based diagnostic tests have been developed for the management of severe hemorrhage, however their main downside is the time necessary to obtain a result, which can be significant (between 40 minutes and an hour) and therefore not be entirely representative of a fastchanging clinical picture. Based on this need of faster results, Point-of-Care tests have been developed and implemented, since they can represent a diagnostic tool that allows a reduction of the time interval before appropriate intervention. They rely on instruments able to determine blood clot formation in whole blood samples upon activation of coagulation with specific reagents, and activation of platelets upon exposure to different drugs. The present review proposes an overview of both the available Point-of-Care tests such as Thrombelastography, for the assessment of blood clot formation, Impedance Aggregometry, for the function of platelets, and those still under improvement or missing entirely.
Patients with coronavirus disease 2019 (COVID-19) frequently experience a coagulopathy associated with a high incidence of thrombotic events leading to poor outcomes. Here, biomarkers of coagulation ...(such as D-dimer, fibrinogen, platelet count), inflammation (such as interleukin-6), and immunity (such as lymphocyte count) as well as clinical scoring systems (such as sequential organ failure assessment SOFA, International Society on Thrombosis and Hemostasis disseminated intravascular coagulation ISTH DIC, and sepsis-induced coagulopathy SIC score) can be helpful in predicting clinical course, need for hospital resources (such as intensive care unit ICU beds, intubation and ventilator therapy, and extracorporeal membrane oxygenation ECMO) and patient’s outcome in patients with COVID-19. However, therapeutic options are actually limited to unspecific supportive therapy. Whether viscoelastic testing can provide additional value in predicting clinical course, need for hospital resources and patient’s outcome or in guiding anticoagulation in COVID-19–associated coagulopathy is still incompletely understood and currently under investigation (eg, in the rotational thromboelastometry analysis and standard coagulation tests in hospitalized patients with COVID-19 ROHOCO study). This article summarizes what we know already about COVID-19–associated coagulopathy and—perhaps even more importantly—characterizes important knowledge gaps.
It has long been recognised that pancreatic cancer induces a hypercoagulable state that may lead to clinically apparent thrombosis. Although the relationship between pancreatic cancer and ...hypercoagulability is well described, the underlying pathological mechanism(s) and the interplay between these pathways remain a matter of intensive study. This review summarises existing data on epidemiology and pathogenesis of thrombotic complications in pancreatic cancer with a particular emphasis on novel pathophysiological pathways. Pancreatic cancer is characterised by high tumoural expression of tissue factor, activation of leukocytes with the release of neutrophil extracellular traps, the dissemination of tumour-derived microvesicles that promote hypercoagulability and increased platelet activation. Furthermore, other coagulation pathways probably contribute to these processes, such as those that involve heparanase, podoplanin and hypofibrinolysis. In the era in which heparin and its derivatives-the currently recommended therapy for cancer-associated thrombosis-might be superseded by direct oral anticoagulants, novel data from mouse models of cancer-associated thrombosis suggest the possibility of future personalised therapeutic approaches. In this dynamic era for cancer-associated thrombosis, the discovery of novel prothrombotic and proinflammatory mechanisms will potentially uncover pharmacological targets to prevent and treat thrombosis without adversely affecting haemostasis.
Extracellular vesicles (EVs) are a family of particles/vesicles present in blood and body fluids, composed of phospholipid bilayers that carry a variety of molecules that can mediate cell ...communication, modulating crucial cell processes such as homeostasis, induction/dampening of inflammation, and promotion of repair. Their existence, initially suspected in 1946 and confirmed in 1967, spurred a sharp increase in the number of scientific publications. Paradoxically, the increasing interest for EV content and function progressively reduced the relevance for a precise nomenclature in classifying EVs, therefore leading to a confusing scientific production. The aim of this review was to analyze the evolution of the progress in the knowledge and definition of EVs over the years, with an overview of the methodologies used for the identification of the vesicles, their cell of origin, and the detection of their cargo. The MISEV 2018 guidelines for the proper recognition nomenclature and ways to study EVs are summarized. The review finishes with a “more questions than answers” chapter, in which some of the problems we still face to fully understand the EV function and potential as a diagnostic and therapeutic tool are analyzed.
It is common knowledge that cancer patients are more prone to develop venous thromboembolic complications (VTE). It is therefore not surprising that patients with hepatocellular carcinoma (HCC) ...present with a significant risk of VTE, with the portal vein being the most frequent site (PVT). However, patients with HCC are peculiar as both cancer and liver cirrhosis are conditions that can perturb the hemostatic balance towards a prothrombotic state. Because HCC-related hypercoagulability is not clarified at all, the aim of the present review is to summarize the currently available knowledge on epidemiology and pathogenesis of non-malignant thrombotic complications in patients with liver cirrhosis and HCC. They are at increased risk to develop both PVT and non-splanchnic VTE, indicating that both local and systemic factors can foster the development of site-specific thrombosis. Recent studies have suggested multiple and often interrelated mechanisms through which HCC can tip the hemostatic balance of liver cirrhosis towards hypercoagulability. Described mechanisms include increased fibrinogen concentration/polymerization, thrombocytosis, and release of tissue factor-expressing extracellular vesicles. Currently, there are no specific guidelines on the use of thromboprophylaxis in this unique population. There is the urgent need of prospective studies assessing which patients have the highest prothrombotic profile and would therefore benefit from early thromboprophylaxis.
From the Department of Medical and Surgical Sciences (PP, EB, PS, RP, DT, AP), Department of Clinical and Experimental Medicine, Group of Clinical Epidemiology (FN), and Department of Cardiothoracic ...and Vascular Sciences (VP), University of Padua, Padua; Department of Internal Medicine, Angiology Unit, Arcispedale Santa Maria Nuova, (AG, MI), Reggio Emilia, Italy
Correspondence: Paolo Prandoni, Department of Medical and Surgical Sciences, 2 nd Chair of Internal Medicine, University of Padua, Via Ospedale Civile 105, 35128, Padua, Italy. E-mail: paoloprandoni{at}tin.it
Background and Objectives: While it has long been recognized that patients with acute unprovoked deep vein thrombosis (DVT) or pulmonary embolism (PE) have a higher risk of recurrent venous thromboembolism (VTE) than that of patients with secondary thrombosis, whether other clinical parameters can help predict the development of recurrent events is controversial. The aim of this investigation was to assess the rate of recurrent VTE after withdrawal of vitamin K antagonists, and to identify clinical parameters associated with a higher likelihood of recurrence.
Design and Methods: We followed, up to a maximum of 10 years, 1626 consecutive patients who had discontinued anticoagulation after a first episode of clinically symptomatic proximal DVT and/or PE. All patients with clinically suspected recurrent VTE underwent objective tests to confirm or rule out the clinical suspicion.
Results: After a median follow-up of 50 months, 373 patients (22.9%) had had recurrent episodes of VTE. The cumulative incidence of recurrent VTE was 11.0% (95% CI, 9.5–12.5) after 1 year, 19.6% (17.5–21.7) after 3 years, 29.1% (26.3–31.9) after 5 years, and 39.9% (35.4–44.4) after 10 years. The adjusted hazard ratio for recurrent VTE was 2.30 (95% CI, 1.82–2.90) in patients whose first VTE was unprovoked, 2.02 (1.52–2.69) in those with thrombophilia, 1.44 (1.03–2.03) in those presenting with primary DVT, 1.39 (1.08–1.80) for patients who received a shorter (up to 6 months) duration of anticoagulation, and 1.14 (1.06–1.12) for every 10-year increase of age. When the analysis was confined to patients with unprovoked VTE the results did not change.
Interpretation and Conclusions: Besides unprovoked presentation, other factors independently associated with a statistically significant increased risk of recurrent VTE are thrombophilia, clinical presentation with primary DVT, shorter duration of anticoagulation, and increasing age.
Key words: venous thrombosis, venous thromboembolism, deep vein thrombosis, pulmonary embolism, anticoagulation, thrombophilia, heparin, warfarin.
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