Low admission protein C levels is a risk factor for disease worsening and mortality in hospitalized patients with COVID-19

Severe acute respiratory syndrome coronavirus 2, coronavirus disease 2019 (COVID-19)-induced infection can be associated with a coagulopathy, findings consistent with infection-induced inflammatory changes as observed in patients with disseminated intravascular coagulopathy (DIC). The lack of prior immunity to COVID-19 has resulted in large numbers of infected patients across the globe and uncertainty regarding management of the complications that arise in the course of this viral illness. The lungs are the target organ for COVID-19; patients develop acute lung injury that can progress to respiratory failure, although multiorgan failure can also occur. The initial coagulopathy of COVID-19 presents with prominent elevation of D-dimer and fibrin/fibrinogen-degradation products, whereas abnormalities in prothrombin time, partial thromboplastin time, and platelet counts are relatively uncommon in initial presentations. Coagulation test screening, including the measurement of D-dimer and fibrinogen levels, is suggested. COVID-19–associated coagulopathy should be managed as it would be for any critically ill patient, following the established practice of using thromboembolic prophylaxis for critically ill hospitalized patients, and standard supportive care measures for those with sepsis-induced coagulopathy or DIC. Although D-dimer, sepsis physiology, and consumptive coagulopathy are indicators of mortality, current data do not suggest the use of full-intensity anticoagulation doses unless otherwise clinically indicated. Even though there is an associated coagulopathy with COVID-19, bleeding manifestations, even in those with DIC, have not been reported. If bleeding does occur, standard guidelines for the management of DIC and bleeding should be followed. Show more

Background The severe inflammatory state secondary to COVID‐19 leads to a severe derangement of hemostasis that has been recently described as a state of disseminated intravascular coagulation (DIC) and consumption coagulopathy, defined as decreased platelet count, increased fibrin(ogen) degradation products such as D‐dimer, as well as low fibrinogen. Aims Whole blood from 24 patients admitted at the intensive care unit because of COVID‐19 was collected and evaluated with thromboelastography by the TEG point‐of‐care device on a single occasion and six underwent repeated measurements on two consecutive days for a total of 30 observations. Plasma was evaluated for the other parameters of hemostasis. Results TEG parameters are consistent with a state of hypercoagulability as shown by decreased values, and increased values of K angle and MA. Platelet count was normal or increased, prothrombin time and activated partial thromboplastin time were near(normal). Fibrinogen was increased and D‐dimer was dramatically increased. C‐reactive protein was increased. Factor VIII and von Willebrand factor (n = 11) were increased. Antithrombin (n = 11) was marginally decreased and protein C (n = 11) was increased. Conclusion The results of this cohort of patients with COVID‐19 are not consistent with acute DIC, rather they support hypercoagulability together with a severe inflammatory state. These findings may explain the events of venous thromboembolism observed in some of these patients and support antithrombotic prophylaxis/treatment. Clinical trials are urgently needed to establish the type of drug, dosage, and optimal duration of prophylaxis. Show more

Impairment of the protein C anticoagulation pathway is critical to the thrombosis associated with sepsis and to the development of purpura fulminans in meningococcemia. We studied the expression of thrombomodulin and the endothelial protein C receptor in the dermal microvasculature of children with severe meningococcemia and purpuric or petechial lesions. We assessed the integrity of the endothelium and the expression of thrombomodulin and the endothelial protein C receptor in biopsy specimens of purpuric lesions from 21 children with meningococcal sepsis (median age, 41 months), as compared with control skin-biopsy specimens. The expression of endothelial thrombomodulin and of the endothelial protein C receptor was lower in the patients with meningococcal sepsis than in the controls, both in vessels with thrombosis and in vessels without thrombosis. On electron microscopical examination, the endothelial cells were generally intact in both thrombosed and nonthrombosed vessels. Plasma thrombomodulin levels in the children with meningococcal sepsis (median, 6.4 ng per liter) were higher than those in the controls (median, 3.6 ng per liter; P=0.002). Plasma levels, protein C antigen, protein S antigen, and antithrombin antigen were lower than those in the controls. In two patients treated with unactivated protein C concentrate, activated protein C was undetectable at the time of admission, and plasma levels remained low. In severe meningococcal sepsis, protein C activation is impaired, a finding consistent with down-regulation of the endothelial thrombomodulin-endothelial protein C receptor pathway. Show more