Thrombopoietin Receptor Agonists in Treatment of Idiopathic Thrompocytopenic Purpura (Primary Immune Thrombocytopenia): Efficacy and Safety in Everyday Clinical Practice

Background & Aims. The use of thrombopoietin receptor agonists (aTPO-r) is a new approach to the treatment of patients with idiopathic thrompocytopenic purpura (ITP) irresponsive to other methods. Data on the efficacy and safety of aTPO-r outside the frames of clinical trials are limited. The aim of the study is to evaluate the efficacy of the therapy in the routine clinical practice as the second and subsequent lines of therapy, as well as the frequency and nature of complications of the treatment in chronic ITP patients. Methods. Data on 58 adult patients (median age: 56 years) with chronic ITP were retrospectively evaluated; 43 (74 %) of them were treated with romiplostim and 15 (26 %) patients received eltrombopag. Two or more lines of prior therapy were ineffective in 19 (33 %) patients (14 from the romiplostim group and 5 from the eltrombopag group). aTPO-r was prescribed and adjusted according to the prescription guidelines. The efficacy of the treatment was assessed based on the platelet response and the possibility of achieving a sustained response after discontinuation of the therapy. Hemorrhagic manifestations were classified according to the WHO bleeding scale. The safety assessment is conducted by identifying adverse events (AEs) and lab test abnormalities. Treatment-related adverse events was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Results. The therapy with aTPO-r was effective in 49 (84 %) patients, including 36 patients (84 %) treated with romiplostim and 13 patients (87 %) with eltrombopag. The median dose to maintain a response was 3.7 mg/kg and 44 mg, respectively. A stable remission was achieved in 4 patients after discontinuation of romiplostim and 1 patient after discontinuation of eltrombopag. aTPO-r resistance was diagnosed in 9 (16 %) patients: 7 (16 %) of them were from the romiplostim group and 2 (13 %) from the eltrombopag group. Complete arrest of bleeding was achieved in 43 (88 %) responders and its reduction to grade I was achieved in the remaining 6 (12 %) of them. The most frequent AEs of romiplostim therapy were headache, arthralgia and dermatitis; and the treatment with eltrombopag caused hepatotoxicity, headache, and nausea. The severity of events did not lead to complete discontinuation of the therapy in any case. Different types of thrombotic complications were diagnosed in 3 patients (5.2 %). Conclusion. The therapy with aTPO-r is an effective and safe method for the treatment of patients with chronic ITP in the second and subsequent lines of therapy

Molecular Genetic Markers and Clinical Characteristics of Essential Thrombocythemia

Background & Aims. The presence of different molecular genetic markers of clonality (mutations in JAK2, MPL, CALR) or their absence (triple negative status, TN) in essential thrombocythemia (ET) indicates a biological heterogeneity of the disease and can determine its clinical forms. The aim was to evaluate the association of molecular genetic markers with the clinical form and the prognosis of ET. Materials & Methods. We analyzed the data of 240 patients with ET at the age of 20–91 years (median age 58.7 years), who were observed in the Russian Research Institute of Hematology and Transfusiology from 1999 to 2016 (median observation period 37.2 months). Results. The JAK2V617F (JAK2+) mutation was found in 182 (75.9 %) of 240 patients. CALR (CALR+) mutations were found in 30 (12.5 %): type 1 (CALR1+) mutations in 13/30 (43.3 %) and type 2 (CALR2+) in 17/30 (56.7 %). MPL (MPL+) mutations were found in only 2 (0.8 %) of 240 patients. None of the mutations were detected in 26 (10.8 %) of 240 patients (TN status). Significantly higher platelet counts were observed in CALR1+ and CALR2+ subgroups during the primary diagnosis of ET compared with JAK2+ and TN groups. The mean platelet counts were 1252 × 109/L for CALR2+ and 1079 × 109/L for CALR1+ vs 841 × 109/L (p < 0.001; p = 0.06) and 775 × 109/L (p < 0.001; p = 0.04) for JAK2+ and TN, respectively. Thrombosis was diagnosed in 50 (27.4 %) of 182 patients of the JAK2+ subgroup, in 8 (30.7 %) of the 26 patients of the TN subgroup, and in 2 (18.2 %) of 11 patients of the CALR1+ subgroup. No thrombosis was found in the CALR2+ and MPL+ subgroups (p < 0.001). In general, the CALR1+ status was characterized as the most favorable in terms of prognosis (5-year overall survival rate of 100 %), compared to the least favorable TN status (5-year overall survival rate of 85 %). Conclusion. Mutations in the CALR gene were characterized by a more favorable prognosis in comparison with JAK2+ and TN, as well as a decrease in the risk and frequency of thrombosis, despite higher platelet counts. TN-status of ET was associated with unfavorable prognosis

Genetic Markers of Hereditary Thrombophilia and Risk of Thrombotic Complications in Patients with Polycythemia Vera

Background. Thrombotic complications are one of the main problems of polycythemia vera (PV) treatment. They significantly impair the quality of life of these patients and may lead to the lethal outcome. A thrombotic event often precedes the diagnosis of this hematological disease. The pathogenesis of thrombosis in myeloproliferative neoplasms, PV, in particular, is a complex one. Prescription of antiaggregants in the absence of thrombosis and anticoagulants after a thrombotic event requires special attention and development of corresponding recommendations. The prescription of anticoagulants is impossible without taking into account the risks of hemorrhagic complications, which are also typical for myeloproliferative neoplasms. Aim. Assessment of the impact of hereditary thrombophilia genetic markers on the risk of thrombotic complications in patients with PV. Methods. The study examined 116 patients with PV, who were screened for markers of hereditary thrombophilia: factor V (G1691A, FV Leiden), prothrombin, methylenetetrahydrofolate reductase (MTHFR), fibrinogen (FI), plasminogen activator inhibitor (PAI-1), and platelet fibrinogen receptor type IIIA (GPIIIA). The incidence of these markers and their role in thrombosis in such patients was investigated. Results. The study provided data on the incidence of hereditary thrombophilia markers in patients with PV. Statistically significant differences in the incidence of these markers and homocysteine level were found between patients with thrombosis and without them. Conclusion. The information about the hereditary thrombophilia markers presence may be useful for the prescription of adequate antiaggregant and anticoagulant therapy for PV patients. Further research in this field is justified and it will probably demonstrate the relevance of hereditary thrombophilia markers as prognostic factors for thrombotic complications risk assessment