FARMACIA, 2021, Vol. 69, 2 219 https://doi.org/10.31925/farmacia.2021.2.5 REVIEW EFFICACY AND SAFETY OF THROMBOPOIETIN RECEPTOR AGONISTS IN MODERN TREATMENT OF IMMUNE THROMBOCYTOPENIA ANDRADA PARVU 1,2 *, OLGA HILDA ORASAN 3 , STEFAN VLAD POP 1,4 , IULIA ANDREA ZSOLDOS 1 , CRISTINA CATANA 1 , IOANA STEFANIA DEAC 1 , ANCA SIMONA BOJAN 1,2 1 Haematology Department, “Iuliu Hațieganu” University of Medicine and Pharmacy, 73 21-Decembrie Boulevard, Cluj- Napoca, Romania 2 Haematology Department, “Prof. Dr. Ion Chiricuţă” Oncological Institute, 73 21-Decembrie Boulevard, Cluj-Napoca, Romania 3 4 th Medical Department, “Iuliu Hațieganu” University of Medicine and Pharmacy, 18 Republicii Street, Cluj -Napoca, Romania 4 Emergency County Hospital, 2 Ravensburg Street, Satu-Mare, Romania *corresponding author: parvuandrada@hotmail.com Manuscript received: June 2020 Abstract Immune thrombocytopenia (IT), characterized by isolated platelet decrease and bleeding, could be primary or secondary to infections, autoimmune diseases, drugs. Classical treatments for IT are corticosteroids, immunoglobulins (1 st line) and splenectomy, immunosuppression (2 nd line), therapies based on decreasing platelets’ destruction. Thrombopoietin receptor agonists (TRA), romiplostim, eltrombopag and avatrombopag, modern drugs used for refractory patients, increase platelets production. The aim of the article is a review of literature based on 59 scientific articles regarding the efficacy and safety of TRA in primary IT. This review is helpful to specialists, given the limited experience with these drugs, approved in 2008 in the United States and in 2009 in Europe. TRA have shown good efficacy, treatment leading to increased platelet counts, decreased haemorrhagic episodes, reduced concomitant medication. TRA were well tolerated, the adverse effects reported were medullary fibrosis, thrombosis, headache, rhinopharyngitis, hepatocitolysis, fatigue. Rezumat Trombocitopenia imună (TI), caracterizată prin scăderea numărului de trombocite şi hemoragii, poate fi primară sau secundară unor infecţii, boli autoimune, medicamente. Tratamentele clasice scad distrucţia trombocitelor şi sunt reprezentate de corticoizi şi imunoglobuline (linia I), splenectomie şi imunosupresie (linia II). Agoniştii receptorilor de trombopoietină (ART), romiplostin, eltrombopag și avatrombopag, medicamente moderne destinate cazurilor refractare, stimulează trombocitopoieza. Acestă analiză sistematică de literatură se bazează pe 59 articole de specialitate și analizează eficacitatea şi siguranţa ART în TI primară. Lucrarea este utilă având în vedere experienţa limitată cu aceste medicamente aprobate în 2008 în Statele Unite şi în 2009 în Europa. ART au dovedit o bună eficienţă, crescând numărul de trombocite, scăzând numărul şi amploarea episoadelor hemoragice, reducând medicaţia concomitentă. ART sunt bine tolerate, efectele adverse constând în mielofibroză, tromboze, cefalee, rinofaringită, hepatocitoliză, fatigabilitate. Keywords: thrombopoietin receptor agonists, immune thrombocytopenia Introduction Immune thrombocytopenia (IT) is an autoimmune disease characterized by isolated thrombocytopenia (platelet count under 100.000/μL) in the absence of other causes or disorders that may be associated with thrombocytopenia. The dominant clinical manifestation is bleeding, which generally correlates with the severity of thrombocytopenia [7, 18, 19, 58]. According to the classical pathogenetic theory, immune thrombocytopenia is mediated by autoantibodies, platelet antibodies that accelerate platelet destruction and inhibit their production. New pathogenetic theories are based on multiple immune mechanisms of platelet and their progenitors’ destruction (complement mediated cytotoxicity of T lymphocytes and CD4 + mediated cytotoxicity). Another modern idea is that platelet production is variably impaired, antibodies could contribute to megakaryocyte destruction, induce apoptosis, impede platelet release, or promote intra- medullary phagocytosis [7, 18]. The disease could be primary (idiopathic) or secondary to infections (eg. Helicobacter pylori, B or C hepatitis, HIV), to other autoimmune diseases (systemic erythematous lupus, rheumatoid arthritis or other collagenous pathologies) or to certain drugs. In addition, environmental and genetic factors may impact