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Watch "COVID Clotting Confusions" N e w ! A B M P P o c k e t P a t h o l o g y a t w w w. a b m p . c o m / a b m p - p o c k e t - p a t h o l o g y - a p p . 33 When all goes well, we form and melt clots all the time, in appropriate responses to tissue damage or other factors. But when we form more clots than we can melt, we are at risk for complications like thrombi (clots that form onsite and can become big enough to block blood flow) or emboli (fragments of thrombi or debris that travel through vessels to other locations). Many things can upset our hemostatic processes. Heart disease, trauma, pregnancy, autoimmune disease, inflammation, and some types of cancer can all cause pro- clotting imbalances in these mechanisms. But the focus of this article is the hemostatic derangement that occurs in the presence of systemic infection with SARS-CoV-2, the virus that causes COVID-19. I am deeply grateful to Dawn, a generous massage therapist and COVID-19 survivor, who experienced a version of this process, and shared her story (see Dawn's Timeline). WHEN IT ALL GOES WRONG: HEMOSTATIC DERANGEMENT We know that SARS-CoV-2 first targets the lungs in most patients, but we also know it doesn't always stop there. It turns out this virus can attack any cells with a membrane receptor site called ACE-2. This includes alveolar cells, but also myocardial cells, kidney cells, the intestinal lining, and (here is the link between COVID-19 and clotting disorders) the endothelial layer of blood vessels—in arteries, veins, and capillaries. And these attacks lead to inflammation (endotheliitis) and damage to the inner lining of blood vessels. In some people, this damage triggers an extreme inflammatory reaction called a cytokine storm—this is a topic addressed in Til Dawn's Timeline Dawn, a massage therapist from Texas, was kind enough to chat with me about her experience. Here is her timeline of interactions with COVID-19 and its complications: • December 2019: Dawn takes care of her brother who is in the hospital with an undiagnosed infection. He needs a ventilator, dialysis, and other interventions. Weeks later his health-care team agrees that he had all the signs and symptoms of COVID-19 before it was officially recognized in that part of the country. • March 19, 2020: Dawn wakes with a feeling of heaviness in her chest. She has had bronchitis in the past, and she assumes this is another bout. She is bedridden for three days, and then symptoms subside. • March 25, 2020: Dawn has no fever, cough, congestion, or trouble breathing, but she has debilitating fatigue and needs two naps a day just to function. She has a sudden onset of extreme muscle soreness in her upper body, and spends much of the next few weeks with pain-relieving lotion on her trunk and arms. During a bath, she notices bright pink spots all over her legs. These get progressively larger over the next several days. • April 16, 2020: Many of the pink spots have converged into large wheals. They are intensely itchy, like "ants biting." Her legs are bilaterally swollen at the end of every day. In a consultation with a "tele-doc," she is counseled to cut down on her activity (she had been walking four miles every day), to raise her legs whenever she rests, and to take a baby aspirin daily. (Although her doctor doesn't ask about this, she is also experiencing severe and prolonged bleeding in her mouth when she brushes her teeth.) • April 24, 2020: After mild exercise, large bruises form over the wheals on Dawn's legs. She has tingling sensations in her upper lip that persist for a few days. • April 25, 2020: Dawn is tested for COVID-19. Her nasopharyngeal swab is negative, but her serum antibodies are positive. This indicates that she has had the infection in the past, but the viral population in her upper respiratory tract is low. • April 30, 2020: Dawn's rash is 95 percent gone, and she is almost at normal activity levels. • May 12, 2020: Dawn's rash on her legs flares up again, and she now has dark purple spots on her toes: COVID-toe.

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