English

Olga An

Immune thrombocytopenia: what can the systems biology and systems physiology offer?

Immune thrombocytopenia (ITP) is an acquired bleeding disorder of autoimmune pathophysiology. The causes of ITP could be related to other pathology (viral, bacterial, or systemic), or ITP could develop without any apparent reason. While the immune system dysregulation mechanisms in ITP were described, its etiology remains unclear. Moreover, all existing treatment approaches are not specific for ITP, and its action is highly patient- specific. Here we describe recent findings in the origins and development of ITP and discuss novel experimental and theoretical approaches to diagnosing ITP and predicting therapy effects.

Schematic of immune thrombocytopenia mechanisms. The thrombocytopenia in patients could be caused by both T-cells cytotoxicity (CTLs are more active because T-regulatory cells and T-helpers provide dysregulated stimuli) and B-cells antibody production (plasma cells are producing antiplatelet antibodies of IgG and IgM classes; B-regulatory cells provide more activating signals to B-cells to produce antibodies). CTLs specifically attack platelets and induce their apoptosis. Antibodies from plasma cells opsonize platelets. Consecutively, opsonized platelets are eliminated through the spleen. CTLs – cytotoxic T-lymphocytes; Treg – T-regulatory cell; Th – T-helper; Breg – B-regulatory cell; BAFF – B-cell activating factor.
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#autoimmunity#ITP#platelets#acute/chronic ITP#computational modeling#murine models

A strong correlation exists between platelet consumption and platelet hyperactivation in COVID-19 patients. Pilot study of the patient cohort from CCH RAS Hospital (Troitsk).

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It is known that in COVID-19, hypercoagulation and sometimes thrombocytopenia are related to disease severity. There is also controversial data on platelet participation in COVID-19 pathology. We aimed to determine the degree of platelet hyperactivation in COVID-19 patients. Whole blood flow cytometry with Annexin-V and lactadherin staining ("PS+ platelets") was utilized. Additionally, a stochastic mathematical model of platelet production and consumption was developed. Here we demonstrated that the percentage of PS+ platelets in COVID-19 patients was twofold that of healthy donors. There was a significant correlation between the amount of PS+ platelets and the percentage of lung damage in patients. No connection was found between platelet senescence and hospital therapy or patients' chronic diseases, except for chronic lung disease. Although no thrombocytopenia was observed in patients, the observed increase in platelet size (FSC-A parameter in flow cytometry) could indicate that platelet age is decreased in patients. The developed computational model of platelet turnover confirms the possibility of intense platelet consumption without noticeable changes in platelet count. We conclude that the observed platelet hyperactivation in COVID-19 could be caused by platelet activation in circulation, leading to platelet consumption without significant thrombocytopenia.

Computational model of platelet production in the presence of COVID-19 induced thrombosis. A – Detailed scheme of the model (most sensitive reactions are highlighted in red). B – Dependence of the average platelet count (green curve and dots) and platelet size (red curve and dots) from the platelet consumption index in the model. Platelet number and size in the absence of consumption lie in the areas, highlighted by green and red rectangles correspondingly. C – Platelet size distribution in the absence (green bars) and the presence (red bars) of consumption (with consumption index set to 2). Whiskers on all plots represent SD.
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#COVID-19#platelets#coagulation#inflammation#hyperactivation