The admission to a hospital of the secretary general of Vox, Javier Ortega Smith, has sown confusion about the appearance of thrombi, a symptomatic manifestation of COVID-19 that is not mysterious at all, although it can be worrying. Blood clotting is an organic defense mechanism that emerged about 430 million years ago. This mechanism has represented an evolutionary advantage in vertebrates.
Humans, like the rest of vertebrates, are exposed to hemorrhages and we cope with them thanks to thrombogenesis. The first humans were constantly in danger of bleeding after suffering terrible wounds in hunting or war. We are the descendants of those ancestors and that is why we are thrombogenic by nature.
But in the hemorrhage versus thrombogenesis antagonism, a typical case of pleiotropic paradox occurs: at advanced ages we die many more times from thrombosis than from hemorrhage. The formation of thrombi, which has saved our lives so many times by containing bleeding, takes its toll on diseases that cause endothelial abnormalities, including COVID-19.
Weeks ago alarmist news appeared that emphasized the “mysterious” proliferation of thrombi that was killing those infected by coronavirus in which it caused cerebral and heart infarcts, as well as ischemic skin lesions. As it could not be less in these times, the networks generated a hoax denied by Newtral.
In cases of COVID-19 there is no mystery whatsoever in the formation of blood clots within small vessels. From the beginning of the pandemic, Chinese scientists detected this fact. On January 31 pathologists from Wuhan hospitals had already begun to perform autopsies, the results of which were collected on March 9 in the journal The Lancet .
The article, which analyzes information from 191 Chinese patients, 54 of whom died during the month of January, documented the alteration of coagulation that led to the formation of thrombi in the most seriously ill, a symptom that the Chinese authorities had already included in the disease management manual published on February 18.
Subsequent published studies with Dutch, Italian and American patients confirmed what physicians around the world already suspected: one of the poor prognostic markers in COVID-19 was tests that detected thrombus formation.
For this reason, the patients were systematically treated with low molecular weight heparins, anticoagulants widely used in all types of situations with risk of thrombus formation.
Why does thrombosis occur?
COVID-19 is a disease that targets the glandular epithelia of the respiratory and digestive tracts, but the virus also has endothelial tropism. It is a viral infection associated with a systemic inflammatory response, acute interstitial pneumonia and the activation of coagulation both in the lungs and in the rest of the organs.
Blood is a liquid tissue in unstable equilibrium, which when it is outside our body coagulates. It also coagulates inside, when the circulation in varicose veins stagnates (thrombosis), or when the veins become inflamed (thrombophlebitis). When blood is in circulation, coagulation is minimal and is neutralized by the fibrinolytic system.
Clots or thrombi are named after thrombin, an enzyme that converts fibrinogen to fibrin . Fibrinogen is a soluble protein in blood plasma that acts as a precursor to fibrin, a fibrillar protein that precipitates forming a network in which elements of the blood are trapped, forming clots and thrombi. When a wound occurs, the adrenergic response and vascular damage (endothelial injury) release thrombin and other molecules that trigger a cascade of clotting factors: the fibrin thrombus grows and this acts as a kind of glue plugging the wounds.
In turn, fibrin is degraded by another defense system, the fibrinolytic system, with the formation of a marker molecule for this activity: the D-dimer. The presence of D-dimer in laboratory tests at certain concentrations is indicative of the existence of abnormal fibrin levels and, therefore, of thrombosis, that is, of the formation of blood clots in arteries or veins.
Chinese researchers had already published on March 9 the relationship between D-dimer and the severity of COVID-19. The graph above shows how, as the days go by, the risk of thrombus formation increases in patients who are about to die, the indicator of which is the increase in D-dimer levels.
Both the respiratory and digestive epithelial cells, as well as the endothelial cells that line the entire internal surface of the blood vessels, have locks (receptors) that are opened by SARS-CoV-2. The key to the virus is a spiculated protein from its capsule. The virus enters the body through the nose, mouth, or eyes and then attaches to epithelial and endothelial cells that have numerous ACE2 receptors on their outer membrane.
Both the epithelial cells of the pulmonary alveoli (pneumocytes) and the vascular endothelium have ACE2 receptors in abundance. This receptor is the lock that fits perfectly with the spiculated protein of the virus, so that these cells open their doors wide to the entry of the coronavirus, which causes endothelitis, that is, an inflammation of the vascular endothelium ( in the image above).
How do you combat thrombus formation?
The fact that coagulopathy occurs in patients with COVID-19 has promoted the consideration of antithrombotic strategies, especially in patients admitted to the ICU and show organ damage or ischemic episodes. Although the best antithrombotic strategy has not yet been established, it appears that low molecular weight heparins at prophylactic or intermediate doses are indicated when D-dimer values are higher than normal. Therapeutic anticoagulation is reserved for cases in which a clear local or systemic thrombotic pathology is seen.
Regarding the use of aspirin that some social networks advocate, we refer to this forceful and enlightening article. Aspirin as an antiaggregant reduces the thrombotic risk of atheromas, but it does not even serve to cushion the thrombi caused in economy class syndrome or traveler’s thrombosis.
Authors:
Manuel Peinado Lorca. University professor. Department of Life Sciences and Researcher at the Franklin Institute for North American Studies, University of Alcalá.
José Miguel Sanz Anquela. Associate Professor in Health Sciences. Department of Medicine and Medical Specialties, University of Alcalá.
This article was originally published on The Conversation. Read the original.
