Thrombopoietin receptor agonist romiplostim in refractory thrombocytopenia as a bridging therapy to the second allogeneic stem cell transplantation

Thrombopoietin (TPO) receptor agonist romiplostim mimic the action of TPO and stimulate the activation, proliferation and maturation of megakaryocytes, resulting in an increase in circulating platelet counts. In this work, we present a patient with a Ph-negative chronic myeloid leukemia (CML) with refractory thrombocytopenia treated with romiplostim as a bridging therapy to the second allogeneic stem cell transplantation (alloSCT). A 56-year old male patient was diagnosed with an atypical Ph-negative CML. One year after the diagnosis he underwent alloSCT from HLA-matched unrelated donor, but had early graft rejection, with severe bleeding diathesis, anemia and thrombocytopenia refractory to transfusion therapy. In addition to daily platelet transfusions (sometimes 2 times per day), he received tranexamic acid and intravenous immunoglobulins. Since the severe thrombocytopenia persisted, romiplostim was introduced as subcutaneous once per week treatment. After two weeks of romiplostim therapy, platelet count increased and the need for platelet transfusions decresed, and he was further followed up in outpatient setting receiving romiplostim as a bridging therapy to his second alloSCT that he received latter. This work describe an unusual use of the TPO receptor agonist as a bridging therapy between two alloSCTs to treat severe refractory thrombocytopenia

Biologic therapy and pregnancy – a tertiary center experience

Biološka se terapija primjenjuje u liječenju upalnih reumatskih bolesti posljednjih desetak godina čime se znatno unaprijedila kontrola aktivnosti bolesti. Sigurnost primjene biološke terapije u pretkoncepcijskom razdoblju te tijekom trudnoće i laktacije veoma je važna pri planiranju liječenja mladih bolesnica. Ni Američka agencija za hranu i lijekove ni Europska agencija za lijekove do danas nisu nijedan biološki lijek proglasile sigurnim u trudnoći. Europska liga protiv reumatizma i Britansko reumatološko društvo predložili su smjernice za liječenje reumatoloških bolesnica tijekom trudnoće i laktacije, dok Američko reumatološko društvo trenutačno izrađuje smjernice za terapijski pristup u trudnoći. S druge strane, objavljeni su mnogi radovi o ishodima trudnoća u bolesnica liječenih inhibitorima faktora tumorske nekroze i drugom biološkom terapijom, s malim brojem neželjenih ishoda. Cilj je ovog rada bila analiza primjene biološke terapije u bolesnica koje su planirano ili neplanirano zanijele za vrijeme liječenja u našoj ustanovi te ishoda tih trudnoća. Naši se rezultati ne razlikuju od dosad objavljene literature. Petnaest prikazanih bolesnica primalo je jedan od blokatora tumorske nekroze-α, a jedna bolesnica blokator interleukina- 6 tijekom trudnoće ili neposredno prije začeća. Samo su dvije bolesnice poštovale preporučeni minimalni period od obustave terapije do začeća. Od navedenih 16 bolesnica 3 su imale medicinski indiciran prekid trudnoće: jedna zbog teške malformacije ploda, a dvije zbog terapije konvencionalnim lijekovima koji modificiraju bolest, a kontraindicirani su u trudnoći.Treatment of inflammatory rheumatic diseases and control of disease activity have considerably improved after the introduction of biologic therapy over a decade ago. The safety profile of biologic therapy in the preconception period as well as during pregnancy and lactation is neccessary to consider when planning the treatment of young female patients. Neither the Food and Drug Administration Agency nor the European Medicines Agency have declared biologic therapy safe during pregnancy. Both the European League Against Rheumatism and the British Society for Rheumatology proposed guidelines for the treatment of female rheumatology patients during pregnancy and lactation, and the American College of Rheumatology is currently developing guidelines for the therapeutic approach during pregnancy. On the other hand, there are numerous publications of pregnancy outcomes in patients treated with biologic therapy, with a small number of adverse effects. We analyzed the modalities of biologic therapy and pregnancy outcomes in patients treated at our Department, during planned and unplanned pregnancies. Our results do not differ from the literature published to date. Among the patients described here, 15 were treated with an inhibitor of tumor necrosis factor-α and one with an IL-6 inhibitor during or just before pregnancy. Only 2 patients stopped biologic therapy in compliance with the guidelines. Of the 16 aforementioned patients, 3 had to undergo medically-induced abortion; one patient because of a severe fetal malformation and the other two patients because they had bee

Immune thrombocytopenia

Imuna trombocitopenija (ITP) je stečena, imunološki posredovana bolest odraslih i djece, čija je glavna karakteristika, prolazni ili trajni, različiti stupanj trombocitopenije. Broj trombocita manji od 100 x 109/L uzima se kao granična vrijednost za dijagnozu ITP-a. Dijeli se na primarnu i sekundarnu. Primarna ITP je ona koja se javlja bez poznatog uzroka, dok je sekundarna nastala temeljem podležeće osnovne bolesti. Klinička slika varira od asimptomatskih formi, preko mukokutanih krvarenja, do mogućeg životno ugrožavajućeg krvarenja, s intrakranijalnim krvarenjem kao najtežom formom. Dijagnostika primarnog ITP-a temelji se na isključivanju drugih, mogućih uzroka trombocitopenije (poput virusnih bolesti, imunodeficijencije, autoimunih ili limfoproliferativnih bolesti, primjene antitrombocitnih i drugih lijekova), jer specifični dijagnostički test ne postoji. Detaljno uzeta anamneza i klinički pregled prvi je korak u daljnjoj dijagnostici, a kompletna krvna slika i periferni razmaz krvi trebali bi pokazati samo izoliranu trombocitopeniju, bez drugih patoloških promjena. Terapijski plan treba individualizirati; osim vrijednosti trombocita i krvarećih manifestacija, drugi čimbenici poput životnog stila, dobi, lijekova i komorbiditeta, pridonose odluci je li liječenje potrebno. Prva terapijska linija su kortikosteroidi, s ili bez intravenskih imunoglobulina. U kroničnom tipu ITP-a često su nužne druge terapijske linije, poput splenektomije, agonista trombopoetinskih receptora, rituksimaba, ili drugih imunosupresiva. Sveukupno gledajući, ITP je bolest koja može varirati od asimptomatskih do teških kliničkih slika, od samo limitirajuće do kronične bolesti. U evaluaciji i liječenju bolesti, treba se voditi preporučenim smjernicama, ali isto tako prilagoditi terapijski plan, koji će najviše odgovarati individualnom bolesniku.Immune thrombocytopenia (ITP) is an acquired, immune-mediated disease of adults and children, whose main characteristic is a transient or persistent thrombocytopenia of a different degree. A platelet count less than 100 x 109/L is established as the threshold for ITP diagnosis. It is classified as a primary or secondary form. Primary ITP is the one that occurs without known cause, while secondary ITP is caused by underlying disease. Clinical presentation varies from asymptomatic forms, through mucocutaneous bleeding, to life threatening bleeding, with intracranial bleeding as the most severe form. Diagnosis of primary ITP is based on the exclusion of other possible causes of thrombocytopenia (such as viral diseases, immunodeficiency, autoimmune or lymphoproliferative diseases, use of antithrombotic or other drugs) because a specific diagnostic test does not exist. Carefully taken patient's history and physical examination are the first steps in the further diagnostic process. Peripheral blood count and peripheral blood smear should show isolated thrombocytopenia without other pathological changes. The therapeutic plan should be individualized; besides platelet count and bleeding manifestations, other factors like lifestyle, age, medication and comorbidities, contribute to decision whether the treatment is needed or not. The first-line treatment are corticosteroids, with or without intravenous immunoglobulins. The chronic ITP often requires other treatment lines, such as splenectomy, thrombopoietic receptor agonists, rituximab, or other immunosuppressants. Overall, ITP is a disease that may vary from asymptomatic to severe clinical forms and from the self-limited to the chronic illness. In evaluation and management of ITP, the recommended guidelines should be followed, but also adapted to the treatment plan that will suit the individual patient the best

Immune thrombocytopenia

Imuna trombocitopenija (ITP) je stečena, imunološki posredovana bolest odraslih i djece, čija je glavna karakteristika, prolazni ili trajni, različiti stupanj trombocitopenije. Broj trombocita manji od 100 x 109/L uzima se kao granična vrijednost za dijagnozu ITP-a. Dijeli se na primarnu i sekundarnu. Primarna ITP je ona koja se javlja bez poznatog uzroka, dok je sekundarna nastala temeljem podležeće osnovne bolesti. Klinička slika varira od asimptomatskih formi, preko mukokutanih krvarenja, do mogućeg životno ugrožavajućeg krvarenja, s intrakranijalnim krvarenjem kao najtežom formom. Dijagnostika primarnog ITP-a temelji se na isključivanju drugih, mogućih uzroka trombocitopenije (poput virusnih bolesti, imunodeficijencije, autoimunih ili limfoproliferativnih bolesti, primjene antitrombocitnih i drugih lijekova), jer specifični dijagnostički test ne postoji. Detaljno uzeta anamneza i klinički pregled prvi je korak u daljnjoj dijagnostici, a kompletna krvna slika i periferni razmaz krvi trebali bi pokazati samo izoliranu trombocitopeniju, bez drugih patoloških promjena. Terapijski plan treba individualizirati; osim vrijednosti trombocita i krvarećih manifestacija, drugi čimbenici poput životnog stila, dobi, lijekova i komorbiditeta, pridonose odluci je li liječenje potrebno. Prva terapijska linija su kortikosteroidi, s ili bez intravenskih imunoglobulina. U kroničnom tipu ITP-a često su nužne druge terapijske linije, poput splenektomije, agonista trombopoetinskih receptora, rituksimaba, ili drugih imunosupresiva. Sveukupno gledajući, ITP je bolest koja može varirati od asimptomatskih do teških kliničkih slika, od samo limitirajuće do kronične bolesti. U evaluaciji i liječenju bolesti, treba se voditi preporučenim smjernicama, ali isto tako prilagoditi terapijski plan, koji će najviše odgovarati individualnom bolesniku.Immune thrombocytopenia (ITP) is an acquired, immune-mediated disease of adults and children, whose main characteristic is a transient or persistent thrombocytopenia of a different degree. A platelet count less than 100 x 109/L is established as the threshold for ITP diagnosis. It is classified as a primary or secondary form. Primary ITP is the one that occurs without known cause, while secondary ITP is caused by underlying disease. Clinical presentation varies from asymptomatic forms, through mucocutaneous bleeding, to life threatening bleeding, with intracranial bleeding as the most severe form. Diagnosis of primary ITP is based on the exclusion of other possible causes of thrombocytopenia (such as viral diseases, immunodeficiency, autoimmune or lymphoproliferative diseases, use of antithrombotic or other drugs) because a specific diagnostic test does not exist. Carefully taken patient's history and physical examination are the first steps in the further diagnostic process. Peripheral blood count and peripheral blood smear should show isolated thrombocytopenia without other pathological changes. The therapeutic plan should be individualized; besides platelet count and bleeding manifestations, other factors like lifestyle, age, medication and comorbidities, contribute to decision whether the treatment is needed or not. The first-line treatment are corticosteroids, with or without intravenous immunoglobulins. The chronic ITP often requires other treatment lines, such as splenectomy, thrombopoietic receptor agonists, rituximab, or other immunosuppressants. Overall, ITP is a disease that may vary from asymptomatic to severe clinical forms and from the self-limited to the chronic illness. In evaluation and management of ITP, the recommended guidelines should be followed, but also adapted to the treatment plan that will suit the individual patient the best

Immune thrombocytopenia

Imuna trombocitopenija (ITP) je stečena, imunološki posredovana bolest odraslih i djece, čija je glavna karakteristika, prolazni ili trajni, različiti stupanj trombocitopenije. Broj trombocita manji od 100 x 109/L uzima se kao granična vrijednost za dijagnozu ITP-a. Dijeli se na primarnu i sekundarnu. Primarna ITP je ona koja se javlja bez poznatog uzroka, dok je sekundarna nastala temeljem podležeće osnovne bolesti. Klinička slika varira od asimptomatskih formi, preko mukokutanih krvarenja, do mogućeg životno ugrožavajućeg krvarenja, s intrakranijalnim krvarenjem kao najtežom formom. Dijagnostika primarnog ITP-a temelji se na isključivanju drugih, mogućih uzroka trombocitopenije (poput virusnih bolesti, imunodeficijencije, autoimunih ili limfoproliferativnih bolesti, primjene antitrombocitnih i drugih lijekova), jer specifični dijagnostički test ne postoji. Detaljno uzeta anamneza i klinički pregled prvi je korak u daljnjoj dijagnostici, a kompletna krvna slika i periferni razmaz krvi trebali bi pokazati samo izoliranu trombocitopeniju, bez drugih patoloških promjena. Terapijski plan treba individualizirati; osim vrijednosti trombocita i krvarećih manifestacija, drugi čimbenici poput životnog stila, dobi, lijekova i komorbiditeta, pridonose odluci je li liječenje potrebno. Prva terapijska linija su kortikosteroidi, s ili bez intravenskih imunoglobulina. U kroničnom tipu ITP-a često su nužne druge terapijske linije, poput splenektomije, agonista trombopoetinskih receptora, rituksimaba, ili drugih imunosupresiva. Sveukupno gledajući, ITP je bolest koja može varirati od asimptomatskih do teških kliničkih slika, od samo limitirajuće do kronične bolesti. U evaluaciji i liječenju bolesti, treba se voditi preporučenim smjernicama, ali isto tako prilagoditi terapijski plan, koji će najviše odgovarati individualnom bolesniku.Immune thrombocytopenia (ITP) is an acquired, immune-mediated disease of adults and children, whose main characteristic is a transient or persistent thrombocytopenia of a different degree. A platelet count less than 100 x 109/L is established as the threshold for ITP diagnosis. It is classified as a primary or secondary form. Primary ITP is the one that occurs without known cause, while secondary ITP is caused by underlying disease. Clinical presentation varies from asymptomatic forms, through mucocutaneous bleeding, to life threatening bleeding, with intracranial bleeding as the most severe form. Diagnosis of primary ITP is based on the exclusion of other possible causes of thrombocytopenia (such as viral diseases, immunodeficiency, autoimmune or lymphoproliferative diseases, use of antithrombotic or other drugs) because a specific diagnostic test does not exist. Carefully taken patient's history and physical examination are the first steps in the further diagnostic process. Peripheral blood count and peripheral blood smear should show isolated thrombocytopenia without other pathological changes. The therapeutic plan should be individualized; besides platelet count and bleeding manifestations, other factors like lifestyle, age, medication and comorbidities, contribute to decision whether the treatment is needed or not. The first-line treatment are corticosteroids, with or without intravenous immunoglobulins. The chronic ITP often requires other treatment lines, such as splenectomy, thrombopoietic receptor agonists, rituximab, or other immunosuppressants. Overall, ITP is a disease that may vary from asymptomatic to severe clinical forms and from the self-limited to the chronic illness. In evaluation and management of ITP, the recommended guidelines should be followed, but also adapted to the treatment plan that will suit the individual patient the best