The coronavirus (COVID-19) is still causing major problems both domestically and internationally, but things may be improving a little. It is interesting that clinicians seem to be learning “new” things about viral infections and how they affect the body. My associate received an email from a colleague of his in Michigan last week showing photos of a patient with necrosis of the tip of a toe, redness of all of his toes, and a particular rash on the foot. He suggested this might be a sign of the coronavirus infection. Recently, there was headline news of an actor in New York whose leg was amputated because of gangrene due to arterial thrombosis thought to be due to the viral infection.1 I guess many clinicians missed learning somewhere along the line, or just forgot, about the relationship between viral infections and coagulation problems. Disruptions of the coagulation system can be seen in both bacterial and viral infections. Some of the problems include disseminated intravascular coagulation, hemolytic uremic syndrome, idiopathic thrombocytopenic purpura, and thrombotic thrombocytopenic purpura. Interestingly, some viral infections can cause bleeding (Ebola virus), some can cause thrombosis (cytomegalovirus), and yet some can cause both bleeding and thrombosis (varicella zoster virus).2 Just as interesting is that both respiratory syncytial virus and adenovirus, which can cause a significant inflammatory reaction in the lung tissue, rarely, if ever, cause clinically significant hemorrhage or thrombosis.2 The thrombotic effects on coagulation can be reflected by thrombocytopenia, deep venous thrombosis, pulmonary embolism, pulmonary infarction, portal vein thrombosis, mesenteric venous thrombosis, microvascular thrombosis, microvascular embolism, and arterial thrombosis.3 The hemorrhagic complications can include thrombocytopenia, disseminated intravascular coagulation, pulmonary hemorrhage, hemoptysis, hematemesis, melena, epistaxis, hematuria, conjunctival bleeding, ecchymosis of the skin, petechial hemorrhage (rash) of the skin, purpura, and uncontrolled bleeding from venipuncture sites. It appears the coagulation problems can be severe or life-threatening whether they are thrombotic or hemorrhagic in nature.
These coagulation problems seem to result from different effects of the virus. The virus can directly affect cells in the body to disrupt the coagulation mechanism. Viral infection of vascular endothelial cells can cause these cells to activate the coagulation system. An interesting effect is when certain viruses invade, infect, and kill megakaryocytes (the cells that become platelets)2; because of this, there can be a reduction in the number of platelets. A second way viruses can affect coagulation is through the production of antibodies that have been found to affect platelets, protein C, antithrombin, and other proteins important in the coagulation system. This results in a reduction of, or malfunction of, proteins necessary for normal coagulation. The third way viruses can affect the coagulation is through the production of inflammatory mediators and cytokines.4 These proteins can profoundly affect the coagulation and fibrinolytic systems, resulting in serious and sometimes fatal thrombosis or hemorrhage. The interaction of viruses and the coagulation system is very complicated and many of the associations are not readily known. For more detailed information, readers may want to look into a review by Goeijenbier et al.2
The treatments for these problems can be confusing and uncertain since the specific effects of the virus on the coagulation system can be varied and actually change during the course of the disease. The effect of the virus in the early stages of the disease can be different than the later stages as the disease becomes more chronic. It is apparent that more information about the pathogenesis of these viral infection coagulation problems is needed. Maybe next time we will not have to be reminded the hard way of the consequences of infectious diseases, especially viral diseases.