A Champion of Host Defense: A Generic Large-Scale Cause for Platelet Dysfunction and Depletion in Infection

Abstract

Thrombocytopenia is commonly associated with sepsis and infections, which in turn are characterized by a profound immune reaction to the invading pathogen. Platelets are one of the cellular entities that exert considerable immune, antibacterial, and antiviral actions, and are therefore active participants in the host response. Platelets are sensitive to surrounding inflammatory stimuli and contribute to the immune response by multiple mechanisms, including endowing the endothelium with a proinflammatory phenotype, enhancing and amplifying leukocyte recruitment and inflammation, promoting the effector functions of immune cells, and ensuring an optimal adaptive immune response. During infection, pathogens and their products influence the platelet response and can even be toxic. However, platelets are able to sense and engage bacteria and viruses to assist in their removal and destruction. Platelets greatly contribute to host defense by multiple mechanisms, including forming immune complexes and aggregates, shedding their granular content, and internalizing pathogens and subsequently being marked for removal. These processes, and the nature of platelet function in general, cause the platelet to be irreversibly consumed in the execution of its duty. An exaggerated systemic inflammatory response to infection can drive platelet dysfunction, where platelets are inappropriately activated and face immunological destruction. While thrombocytopenia may arise by condition-specific mechanisms that cause an imbalance between platelet production and removal, this review evaluates a generic large-scale mechanism for platelet depletion as a repercussion of its involvement at the nexus of responses to infection.

Patients with Congenital Bleeding Disorders Appear to be Less Severely Affected by SARS-CoV-2: Is Inherited Hypocoagulability Overcoming Acquired Hypercoagulability of Coronavirus Disease 2019 (COVID-19)?

“…Viral associated depletion of platelets may represent another characteristic of patients with COVID-19, which can thus lead to potential platelet consumption. 12,13 It should be mentioned that one major limitation of our study is the absence of all coagulation parameters in most patients. Since being male is a risk factor for mortality, one might expect that patients with hemophilia would potentially be at a greater risk of more severe forms of COVID-19, but this was not the experience in our cohort.…”

COVID-19 — Toward a comprehensive understanding of the disease

“…Coagulation disorders are correlated with the severity of bacterial and viral infections [68]. But they can be triggered through systemic or local inflammation involving the endothelium, platelets, and plasma factors [69,70]. Also, in COVID-19 endothelial dysfunction, high von Willebrand factor activity, and probably genetic factors play an essential role in the process.…”

Platelets in Coronavirus Disease 2019

“…Platelets are known to interact directly with several different types of virus through surface integrins, P-selectin, and toll-like receptors, as recently reviewed in detail in this journal by Page and Pretorius. 22 Regarding interactions between SARS-CoV-2 and platelets, however, current knowledge is sparse. Some lessons may be learned from the SARS-CoV and MERS-CoV (Middle East respiratory syndrome coronavirus) outbreaks in 2002 to 2003 and 2012, where similar findings have been described of thrombocytopenia, predominantly mild, in 30 to 50% of patients.…”