key: cord-0791172-fxvkxt3x authors: Zhang, Litao title: Response to ‘all these D‐dimers in COVID‐19’ date: 2020-06-11 journal: J Thromb Haemost DOI: 10.1111/jth.14953 sha: be6b959fad04bf39f146696e764814217791c7b6 doc_id: 791172 cord_uid: fxvkxt3x We appreciate the opportunity to respond to the letter from Dr Thachil[1], who provided an interesting physiological explanation for coagulation‐fibrinolysis balance shifts of the Broncho‐alveolar haemostasis during COVID‐19 infection, and speculated that the extravascular fibrinolysis would be a source of elevated D‐dimers. We appreciate the opportunity to respond to the letter from Dr Thachil[1], who provided an interesting physiological explanation for coagulation-fibrinolysis balance shifts of the Broncho-alveolar haemostasis during COVID-19 infection, and speculated that the extravascular fibrinolysis would be a source of elevated D-dimers. Importantly, when we evaluate and use D-dimer in COVID-19, it should always be aware of that D-dimer should not be a "stand-alone test" or a "one-fit-all test" in managing COVID-19. The COVID-19 associated coagulopathy would be not only caused by lung-specific coagulation disorder, but also mainly caused by systemic inflammatory response syndrome. First, Eventhough the SARS-CoV-2 is primarily a respiratory pathogen; however, local inflammatory response would release proinflammatory factors into the whole blood circulation to stimulate serial reactions, resulting in coagulation activation, organ damage et al [2] . Second, the hypoxia, which was one of the common symptoms in severe Covid-19 also can stimulate thrombosis through increasing blood viscosity and a hypoxia-inducible transcription factor-dependent signaling pathway [3] . Third, the underlying diseases are well known as risk factors of VTE, such as cancer, sepsis. These factors might exacerbate the inflammatory-thrombotic response. The extravascular fibrinolysis relevant to COVID-19 seems to be reasonable. However, in our opinion, among contributions to the elevated D-dimer, the proportion of extravascular fibrinolysis should be relatively small. The primary source of D-dimer should still be endovascular fibrinolysis, even just undetectable microthrombus or just thrombus but was not detected by imaging examination. Of cause, this hypothesis needs further pathological studies to verify. Up to now, D-dimer has been served as one of the most important markers in management of COVID-19. The potential uses of D-dimer in COVID-19 has been revealed in recent studies. 1. D-dimer levels on admission might be used to distinguish patients who have potential high in-hospital mortality [4] . For COVID-19 patients who have markedly raised D-dimers (four-fold increase), admission to hospital and closely monitoring should be considered even in the absence of other severity symptoms. This article is protected by copyright. All rights reserved development [5, 6] . D-dimer might serve as a screening tool when the imaging examination was limited in management of COVID-19. 3. D-dimer might be used to guide whether anticoagulation therapy should be initiated in patients with COVID-19 [7] , and also can be used to evaluate the anticoagulant effect. Whether D-dimer can be used to guide the dose of anticoagulation needs further studies to confirm. However, our team had conducted a randomized clinical trial and found D-dimer can be used to guide the anticoagulation intensity in patients receiving warfarin therapy [8] . 4. D-dimer might be used to monitor disease progression of COVID-19. Previous studies have observed that continues raised D-dimer has been observed to be common in non-survivors of COVID-19 [9, 10] . Thus, dynamic monitoring D-dimer might be used to evaluate whether the situation is getting worse or better. We agreed with Dr Thachil that future studies are needed to evaluate whether D-dimer can be used to guide anticoagulation adjustment, initiating mechanical ventilation, de-escalating critical care support, indicating prognosis of malignancies. The previous studies had suggested that D-dimer could be used to determine the duration of oral anticoagulation in patients with VTE [11] , however, whether this application could still work in post-discharge thromboprophylaxis in the COVID-19 setting remain unknown. Thus, we are carrying out an observational study involved about 200 post-discharge COVID-19 patients to evaluate the correlation between laboratory testing (including D-dimer) and prognosis. Finally, there are many limitations and uncertainties for D-dimer in COVID-19 and other situations, however, we still believed that the use of D-dimer would not only be limited in the traditional applications, but also it would open a new page since the COVID-19 era. Current and future developments in the treatment of virus-induced hypercytokinemia The stimulation of thrombosis by hypoxia D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19 Acute pulmonary embolism in COVID-19 disease: Preliminary report on seven patients Routine Venous Thromboembolism Prophylaxis May Be Inadequate in the Hypercoagulable State of Severe Coronavirus Disease Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy D-dimer to guide the intensity of Accepted Article This article is protected by copyright. All rights reserved anticoagulation in Chinese patients after mechanical heart valve replacement Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan Use of D-dimer in oral anticoagulation therapy