The main clinical presentations of SAR-CoV19 include acute chest syndrome with bilateral pneumonia requiring advanced medical support and intensive care [2]. The infection can be divided into three phases. Mild infection, the pulmonary phase, and the third phase which is an inflammatory phase leading to the most common complication of COVID-19 [3]. SARS-CoV-2 has a high binding affinity for human ACE-2 which broke Angiotensin I. When this peptide hormone is not broken down by ACE-2, it promotes an inflammatory state in the body and causes injury to endothelium [4]. The inflammation is creating a hypercoagulable state. Another hypothetical mechanism may be a Complement activation in viral pneumonia. Other clinical factors, such as hypoxemia, hyperthermia, and hypovolemia, may also increase the state of hypercoagulation in patients treated for COVID-19.
Several thrombotic complications have been described due to this hyperinflammatory response provoked by the SARS-CoV-2; it leads to various types of ischemic and thrombotic events as described in our case report. Acute limb ischemia manifested by acute limb pain, focal hypothermia, skin mottling, absent pulse, or necrosis of the toes, is one of the thrombotic complications of SARS-CoV-2 infection. Patients generally have an elevated D-Dimer and may also have an elevated C-reactive protein. The computed tomographic angiogram of the extremity is often performed. Vascular surgery, interventional radiology consultation, and empiric systemic anticoagulation are the pillars of treatment. Bellosta found, in his study of 20 patients who have been treated for acute limb ischemia during the COVID-19 pandemic, that operative treatment was able to successfully salvage the limb in 12 (70.6%) [5]. A systemic review including primary studies of COVID-19 limb ischemia reported that the mortality rate was around 45% [6]. Another common thrombotic event is the pulmonary embolism (PE). PEs can occur in the third phase of the disease, after the cytokine storm in COVID-19 patients, despite thromboprophylaxis. At first, patients felt a clear improvement but after that, they might have high or increasing oxygen requirements secondary to the development of thromboembolic disease. The incidence of VTE in COVID-19 patients with pneumonia was 25%, and eventually 40% of them died. [7]. The rate of PE in Post-mortem examination of patients with COVID-19 was between 19% and 42% [8, 9]. A French prospective cohort study, has shown that thrombotic complications were diagnosed in 42% of patients with COVID-19 ARDS, and pulmonary embolisms in 16.7% of them. Despite anticoagulation, a high number of patients with COVID-19 ARDS developed life-threatening thrombotic complications, suggesting that anticoagulation targets must be higher than in usual critically ill patients [10]. Coagulopathy in SARS-CoV-2 infection is associated with high mortality. The D-dimer and fibrinogen degradation products (FDP) are the most important markers for the coagulopathy. Biomarkers disorders like low levels of platelets, increased levels of D-dimer, and increasing levels of prothrombin in COVID-19, are associated with poor prognosis. These disorders are explained by thromboembolic complications in patients with severe disease [2]. D-dimer level was significantly higher in PE group. It supposes that the significant increase of D-dimer in severe novel coronavirus pneumonia patients is a reliable index for identifying high-risk groups of VTE. Even more a higher D-dimers, FDP levels, longer PT and APTT (activated partial thromboplastin time) were found in non-survivors pneumonia patients compared to survivors on admission [7, 11, 12]. The contrast-enhanced CT should be used in patients with marked elevation of D-dimer in the course of COVID-19 pneumonia [11].
The prophylactic anticoagulation did not avoid the occurrence of PE in hospitalized patients, and there is a necessity to adapt thromboprophylaxis in patients with SARS-CoV-2 infection. The International Society on Thrombosis and Haemostasis and the American Society of Hematology suggest that all hospitalized COVID-19 patients should receive thromboprophylaxis, or full therapeutic-intensity anticoagulation if such an indication is present. Seriously ill COVID-19 patients should not receive therapeutic-intensity anticoagulation empirically, i.e., in the absence of confirmed venous thromboembolism [13]. A more aggressive individualized anticoagulation strategy might be required in selected cases. The crucial question is which patients must be anticoagulated and how?? A Randomized, Open-label Phase 3 Clinical Trial is ongoing to study prevention of COVID-19 associated thrombosis, coagulopathy and mortality with Low- and High-dose anticoagulation with Enoxaparin [3].