An Overview of the Mechanisms of HIV-Related Thrombocytopenia

Abstract

The first thrombocytopenia cases related to the human immunodeficiency virus (HIV) were described even before its isolation in 1983. Subsequently, multiple mechanisms have been proposed to elucidate the etiology of thrombocytopenia. In addition to other types of cytopenia affecting patients with HIV, thrombocytopenia is observed in about 10–50% HIV patients as one of the first clinical signs of infection. Thus, in this review we aim to summarize the mechanisms proposed for thrombocytopenia since the discovery of HIV, and especially the innovations in the field in recent years. Among the different mechanisms suggested for HIV-related thrombocytopenia, there is emphasis on the accelerated destruction of platelets (PLTs) due to the action of immune complexes, and the presence of anti-PLT and anti-HIV antibodies that cross-react with the PLT membrane. There are also secondary causes of thrombocytopenia, such as the effect of drugs and opportunistic diseases associated with HIV.

Evaluation of Non-Viral Surrogate Markers as Predictive Indicators for Monitoring Progression of Human Immunodeficiency Virus Infection: An Eight-Year Analysis in a Regional Center

“…However, the results of data mining indicated that a combination of TLC, Hb and platelet counts were more reliable measures for monitoring of HIV infected subjects. Thrombocytopenia can occur in HIV-related diseases as a result of platelet destruction by antibodies (25,26). Tong et al assessed hepatitis B treatment guidelines to show that monitoring of platelet counts at baseline and during the course of disease reduced death rates by 20z, suggesting the potential of this marker as a useful tool for prognosis of liver failure and hepatocellular carcinoma.…”

Only severe thrombocytopenia results in bleeding and defective thrombus formation in mice

“…5,6 Other drugs induce thrombocytopenia as a major side effect by affecting platelet production in the bone marrow through direct myelosupression. 7,8 Thrombocytopenia can also be associated with chronic infections such as HIV 9 or hepatitis C 10 or may be an accessory syndrome of hereditary diseases. [11][12][13] Generally, medical treatment of thrombocytopenia with functional platelets is indicated in adult patients with a platelet count of ,30 platelets/nL blood.…”

Platelets as Immune Cells in Infectious Diseases

“…n Induction of activation and phagocytosis -Survival of platelets is shortened after activation by contact with pathogens; for example, in adenovirus infection [223], by HIV Tat protein [90], fungal pathogens (Aspergillus, Candida and Mucormycetes) and secreted compounds of Aspergillus [169,173,175] -STEC enhances platelet phagocytosis by macrophages by inducing downmodulation of platelet CD47 [105] n Induction of apoptosis and cell lysis -Staphylococcus aureus and Escherichia coli, as well as their secreted toxins, trigger degradation of the antiapoptotic protein Bcl-x L in platelets [106] -Bacterial cell wall peptidoglycan stimulates platelet apoptosis [107] -The toxins streptolysin O of Streptococcus pyogenes and pneumolysin of Streptococcus pneumoniae form pores in the platelet membrane [110,111] -Dengue virus infection induces platelet apoptosis [225] n Induction of antiplatelet autoimmune antibodies via molecular mimicry -Antibodies against microbial antigens of HIV, HCV, Dengue virus and Helicobacter pylori cross-react with platelet glycoproteins [136,226] n Affecting thrombopoiesis in the bone marrow -HIV proteins interact with the cell surface of platelet progenitor cells, thus inducing functional defects [227] -Mimicry of viral proteins induces autoimmune antibodies that inhibit megakaryocyte differentiation [228] -Megakaryocytes are infected by HIV [229], HCV [147], CMV [150] and HHV-6 [230] -HIV modifies the cytokine pattern in the bone marrow that is necessary for thrombopoiesis [126] -Production of thrombopoietin, a growth factor for megakaryocyte differentiation, is impaired in HCV-induced liver disease [231] n Sequestration of platelets in the enlarged spleen -HCV-induced portal hypertension results in platelet sequestration in the spleen [137] Impairment of platelet activation/aggregation n Direct interaction -Candidal and cryptococcal cells impair platelet aggregation [232] n Secreted metabolites -Fungal gliotoxin impairs platelet activation and aggregation [166] Resistance to antimicrobial peptides n Modification of net surface rate -S. aureus isolates reduce surface-positive charge thus altering tPMP susceptibility [121], less charge is associated with enhanced resistance …”