ABSTRACT
Background : Coagulopathy is among the most alarming drivers of COVID-19-induced pathology. COVID-19 can result in blockade of the microvasculature in the lungs with microthrombi. While most of the studies concern COVID-19 impact on plasma coagulation, platelet dysfunction has been reported as well. However, the mechanism of platelet malfunctioning in COVID-19 has not been described yet. Aims : To determine the mechanism of COVID-19 induced platelet disfunction. Methods : 46 patients with confirmed COVID-19 (11 non-ICU, 26 ICU, and 9 ECMO) and 26 healthy volunteers were studied (independent ethics committee of NMRC PHOI No 3/2020). Citrated whole blood samples were diluted in Tyrode's buffer and activated by collagen and TRAP-6. Platelets of healthy donors were additionally washed and pre-treated by 0.5 nM of thrombin. Samples were analyzed using BC Navios flow cytometer. Additionally, light transmission aggregometry (AP-2110 SOLAR) of citrated platelet-rich plasma (PRP) with TRAP-6 and fucoidan as activators was conducted. Results : Platelet forward scattering parameter (FSC-A) for COVID-19 patients was significantly increased compared to healthy donors. This parameter reversibly correlated with mild thrombocytopenia observed in some patients. The amount of Annexin-V positive platelets was increased in all patients as well. Relative CD42b and CD62p binding upon activation were decreased, being statistically different in non-ICU and ICU patients. Both of the parameters also correlated to CRP concentration in patient blood plasma. Platelet aggregation was reduced as well. Altogether, platelets demonstrated refractoriness resembling desensitization of receptors. To prove this hypothesis, we performed thrombin pre-treatment of healthy donor platelets, which resulted in a phenotype resembling the COVID-19. Conclusions : Platelets of COVID-19 patients demonstrate refractoriness to activation through PAR1 receptor, probably because of a previous activation with thrombin in circulation. Together with their increased size and fraction of necrotic platelets, this suggests that in COVID-19 platelets encounter thrombin in circulation.
ABSTRACT
One of the most dangerous features of the new coronavirus infection caused by the SARS-CoV-2 virus is the tendency of the hemostasis system of patients to excessive thrombus formation. Among the possible causes of this pathology, both the activation of vascular endothelial cells, leading to the exposure of tissue factor by these cells, and direct activation of the plasma hemostasis were named. Besides, there is a significant change in platelet responses to activation, which is not accompanied by significant thrombocytopenia. The mechanism of platelet dysfunction is rather controversial. On the one hand, there are suggestions that platelets can act as a direct “container” for the virus, thus spreading it throughout the body. On the other hand, the presence of viral RNA in platelets has been demonstrated in only one study, while other authors have obtained the opposite result. Another mechanism of the virus's direct effect on platelets is the penetration of the virus into megakaryocytes and the subsequent violation of thrombocytopoiesis. However, three of the four published works show that platelets from patients with SARS-CoV-2 are in an activated state (the so-called platelet pre-activation). This phenomenon can be caused by the direct influence of the virus and the effect of thromboinflammation in the lungs on platelet functions. Here we review the known data and possible causes of the platelet functionality changes observed in patients with SARS-CoV-2.
ABSTRACT
Blood coagulation abnormalities play an important role in the pathophysiology of COVID-19. However, the specific details of hy-per-coagulation and anticoagulant treatment require further investigations. The objective was to study the indicators of two global tests for the status of the hemostasis system assessment in patients with CO-VID-19 at the time of admission to the clinic (before the start of anticoagulant therapy) and in patients receiving heparin during treatment in the clinic. Material and methods. Global thrombodynamics (TD) and thromboelastography (TEG) tests, as well as coagulogram screening tests (APTT, PT, INR, and fibrinogen) were performed in 136 patients with COVID-19 observed in a hospital setting. All patients received low molecular weight heparins at therapeutic dosages relatively to body weight in accordance with the hospital proto-col for patients with COVID-19. Results. In patients prior to treatment, marked hypercoagulability was observed in all global tests. The main parameters of TD (clot growth rate Vi and Vs) exceeded the reference range in more than 83% and 75% of patients, respectively. Citrate native TEG parameters (R, K, angle α and MA) also showed hyper-coagulation before anticoagulant therapy initiation in 24%, 17%, 48% and 53% of patients, respectively. After the start of treatment, a significant heparin response was obtained for the Vs parameter (the most sensitive to heparin parameter of TD): in 75% of cases, TD recorded hypo-coagulation, in 15% — normocoagulation, and in 10% of measurements, TD parameters continued to be in the hyper-coagulation range. The TEG parameter most sensitive to heparin (angle α) showed a lower response to heparin: it registered hypo-coagulation only in 25% of measurements, in 60% — normoco-agulation, and in 15% the parameter was in the hyper-coagulation range. Conclusion. The significant share of hypercoagulant results (10-15%) may indicate that some patients have not achieved a suffi-cient anticoagulant effect under the therapy.