key: cord-326821-x6comwwl authors: Castelli, Roberto; Gidaro, Antonio title: Abnormal Hemostatic Parameters and Risk of Thromboembolism Among Patients With COVID-19 Infection date: 2020-04-23 journal: J Hematol DOI: 10.14740/jh636 sha: doc_id: 326821 cord_uid: x6comwwl nan increase of D-dimer were often associated with increased mortality or concomitant severe thromboembolic complications. Surprisingly, the authors noted that in the Chinese population, the prevalence of thromboembolic events was particularly elevated among patients with severe lung failure. Similar prevalence was observed by Cui et al in 81 patients admitted to intensive care units (ICUs), where the prevalence of major thromboembolism was around 25% [8] . Low molecular weight heparin (LMWH) or unfractionated heparin (UFH) at prophylactic doses are associated with a reduced 28-day mortality in more severe COVID-19 patients [9] , displaying a sepsis-induced coagulopathy (SIC) score ≥ 4 (40.0% vs. 64.2%, P = 0.029) or D-dimer levels more than six-fold the upper limit of normal (32.8% vs. 52.4%, P = 0.017). Comparably, but slightly higher records of thromboembolic complications (up to about 30%) were observed in Italian patients admitted in ICU (unpublished data). These numbers will be smaller but not less than 2% in all Italian COVID-19 patients hospitalized. Normal incidence of deep vein thrombosis in hospitalized Italian patients without COVID-19 is reported 0.025% [10] . One of the possible reasons for the increased frequency of thromboembolic complications in Italian patients could be attributed to higher median age of 45. 5 [4] compared to China at 37.4 [5] . The thromboembolic complications observed in Italian patients affected by severe COVID-19 include venous thromboembolism and pulmonary embolism (VTE). All thromboembolic complications are documented by compressive ultrasonography (CUS) or computerized axial tomography (CT) scan. All patients share alterations of hemostatic parameters showing: 1) elevated levels of D-dimer (> 1,000 at admission rapidly rising); 2) elevated fibrinogen which may be consumed in the late stage of disease; 3) thrombocytopenia, but less commonly than in classical DIC; and 4) normal or somewhat prolonged partial prothrombin time (PTT) and international normalized ratio (INR). Additional coagulation tests have shown elevated levels of von Willebrand factor and factor VIII, and normal levels of natural anticoagulants such protein C, protein S and antithrombin III (unpublished data). Table 1 shows the most frequent hemostatic alterations observed among Italian patients admitted to ICU for respiratory failure. COVID-19 produces a sort of DIC which is usually characterized by hypercoagulability. The exact pathogenetic mechanism of COVID-19-related DIC is unclear, although inflammatory drive and cytokine release may be responsible for the Hemostatic Parameters and Risks in COVID-19 J Hematol. 2020;9(1-2):1-4 observed coagulation impairment leading to thromboembolic complications. IL-6 may stimulate up-regulation of fibrinogen synthesis by the liver and the virus may bind directly to endothelial cells causing alveolar damage. DIC appears to be a driver of disease severity and correlates with poor outcome [7] . Furthermore, from 40 autopsies, a quarter presented lung specimens macro-thrombosis with typical pattern of pulmonary embolism and more than twothirds showed thrombi in microvessels, associated with diffuse alveolar damage and interstitial lung infiltrates of granulocytes, macrophages and giant platelets (unpublished data). These reports are in agreement with those of Luo et al [11] . All these findings suggest a mechanism of inflammatory-mediated macro-and micro-thrombosis as a pathogenetic mechanism of damage in the setting of severe COVID-19 infection. The hypothesis of improving the clinical outcome of COVID-19 patients by simple and inexpensive antithrombotic drugs is very appealing, but several issues need to be addressed and clarified before adopting an aggressive approach, in particular defining the appropriate timing for the start of the treatment and the dosage, which may impact concomitant medications. While the scientific community is waiting for more robust evidence on the role of heparin or antiplatelet therapy in coagulopathies associated with COVID-19 infection, the Italian Society on Thrombosis and Hemostasis suggests some recommendations [12] , based on expert consensus, for the management of the hemostasis derangement in COVID-19 patients (Figs. 1-3) . 1) Individual risk evaluation together with laboratory tests should , and cannot be recommended as a standard treatment for all COVID-19 patients. 5) Attention should be paid for VKAs and direct oral anticoagulants (DOACs) due to interference with antiviral agents. 6) Strict cooperation between hematologist and all physicians involved in the management of COVID-19 patients is recommended. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding World Health Organization. Coronavirus disease (COV-ID-19) outbreak Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention COVID-19, cytokines and immunosuppression: what can we learn from severe acute respiratory syndrome? Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy Low rate of intrahospital deep venous thrombosis in acutely ill medical patients: results from the AURELIO study Clinical pathology of critical patient with novel coronavirus Pneumonia (Covid-19) COVID-19 and haemostasis: a position paper from Italian Society on Thrombosis and Haemostasis (SISET). Blood Transfus None to declare. None to declare. None to declare. Both the authors equally contributed to analyzing data, writing text and figures. The authors declare that data supporting the findings of this study are available within the article.