Coronaviruses are a large family of enveloped ribonucleic acid (RNA) viruses found in animals such as pigs, camels, bats, and cats. Entering these viruses into the human body can cause mild to moderate upper respiratory illnesses [13]. Several of these coronaviruses are known worldwide, including acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and SARS-CoV-2, which often lead to severe and deadly diseases in humans [13].
Patients with COVID-19 often have respiratory symptoms, which make it hard to distinguish from pulmonary embolism (PE) in severe cases. Studies have shown that coronaviruses increase the risk of arterial and venous thromboembolism by causing inflammatory reactions, immobility, hypoxia, and disseminated intravascular coagulation (DIC) in patients [14]. The co-occurrence and clinical symptomatic overlaps between pulmonary embolism and COVID-19 has made the diagnosis and treatment of PE more difficult. The presence of COVID-19 pneumonia can be easily detected with RT-PCR and CT scan [15, 16]. However, it is much more difficult to confirm PE. This is because factors such as lactate dehydrogenase, ferritin, C-reactive protein, and interleukin levels that influence pro-inflammatory and hypercoagulability processes increase in patients with coronavirus [17, 18]. In addition, recent studies have shown that levels of D-dimer and fibrinogen and fibrin degradation products increase in patients with COVID-19 [19]. It has also been shown that even in the absence of pulmonary embolism in patients with COVID-19, the level of D-dimer increases [18]. An increase in D-dimer (> 1 mg/dL) may indicate mortality in these patients but is not a reliable indicator in the diagnosis of venous thromboembolic [5, 20]. As a result, CT angiography can be helpful in diagnosing VTE in patients with coronavirus [21].
The coagulation mechanism in COVID-19 is unknown. Some theories introduce cytokines as possible factors in the coagulation process in this disease, while others believe that hepatic dysfunction may be involved [22]. Regardless of the coagulation mechanism in patients with coronavirus, it is known that the incidence of thrombosis increases in these patients and so that this coagulation often extends to intravascular coagulation and this expansion results in venous and arterial thrombosis. In addition, it has been shown that 71.4% of patients who died of COVID-19 met the criteria for diffuse intravascular coagulation [23]. Many patients with COVID-19 face sepsis and septic shock [24]. In the septic process, DIC is a major cause of organ dysfunction, so undergoing anticoagulant therapy in this situation can be very challenging [25].
There are currently no specific criteria for the use of anticoagulants in COVID-19 patients. Therefore, more clinical trials are needed to determine whether all patients with coronavirus need to be treated with anticoagulants. In general at this point, using PE prophylaxis based on clinical manifestations and D-dimer level, even in mild cases of COVID-19 seems to be important and necessary [10].
Due to the lack of sufficient information, using or not using anticoagulants to improve the overall symptoms of the disease and its complications in patients with COVID-19 is still highly controversial [26]. Two recent published studies by Klok et al. and Middeldorp et al. advised against prophylactically initiating treatment-dose anticoagulation in all patients with COVID-19 and in opposite recommended using a lower threshold for proper diagnostic tests in assessing thrombotic complications including deep vein thrombosis and PE [27, 28].
Thus, two aims are recommended to be considered in the treatment of patients with COVID-19: the first goal is to protect the organs and timely diagnosis of events caused by the disease and the second goal is to strengthen the immune system to prevent the formation of cytokine storms and blood clotting. Further research into clinical trials is needed to clarify whether prophylactic treatment with anticoagulants leads to clinically beneficial outcomes in patients with COVID-19 infection.