RARE DISEASE
Essential thrombocythemia
Essential thrombocythemia
Essential thrombocythemia
Synonyms: ET, Essential thrombocytosis
Synonyms: ET, Essential thrombocytosis
Synonyms: ET, Essential thrombocytosis
Drug discovery
11
drugs
With orphan designations
Overview
Essential Thrombocythemia (ET) is a Philadelphia-negative myeloproliferative neoplasm characterized by sustained thrombocytosis (>450,000/mcL), thrombotic/hemorrhagic complications, and constitutional symptoms. Diagnosis requires exclusion of reactive causes and other MPNs, with mutations in JAK2 (50%), CALR (23.5%), or MPL (5%) supporting clonal origin [1][6][15]. Management focuses on thrombosis prevention, with disease progression risks including myelofibrosis (13%) and acute leukemia (<2%) [1][6][12].
Therapies
Low-risk: Low-dose aspirin (81–100 mg/day) for microvascular symptoms/thrombosis prevention [3][16][19]
High-risk: Cytoreduction (hydroxyurea, pegylated interferon-α) ± aspirin; anagrelide/ruxolitinib for refractory cases [3][5][13]
Cardiovascular risk factor optimization (e.g., hypertension, diabetes control) [1][8][16]
Categories: rare hematological diseases, rare neoplastic diseases, rare transplant-related disorders
Research Papers
1,682 drug discovery papers about Essential thrombocythemia, with 2 first-in-class and 35 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,682 drug discovery papers about Essential thrombocythemia, with 2 first-in-class and 35 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-13 | Hematological trajectories and pregnancy complications in essential thrombocythemia and polycythemia vera
Abstract Women with essential thrombocythemia (ET) and polycythemia vera (PV) are at increased risk of pregnancy complications. During pregnancy, hematologic parameters tend to approach normal values, and previous studies have reported that a greater decline in platelet counts in ET is associated with reduced risk of complications. In this study, we examined longitudinal trajectories of platelet count, hemoglobin, hematocrit, and leukocyte count during pregnancy, characterized pregnancy outcomes, and investigated the association between platelet trajectories and preeclampsia. We established a longitudinal cohort of pregnant women with ET and PV in the Capital Region and Region Zealand between 2010 and 2024, using data from regional laboratory information systems and Danish health registries. In total, 41 ET and 5 PV pregnancies in 35 women were included. The mean age at MPN diagnosis was 30.1 years in women with ET and 34.1 years in women with PV. In ET pregnancies, platelet counts, hemoglobin, hematocrit and leukocyte count changed by − 44%, − 5%, − 12% and + 55%, respectively, from baseline to delivery, and in PV pregnancies − 36%, − 26%, − 25% and + 47%, respectively. Overall, 29% of ET pregnancies had a maternal complication, with preeclampsia being the most common (12%). ET women who developed preeclampsia had significantly higher platelet counts before pregnancy and experienced a greater decline in platelet counts during pregnancy than women without preeclampsia. Thus, hematologic trajectories during pregnancy may help identify women at increased risk of preeclampsia.
2026-08-09 | The thrombopoietin receptor in myeloproliferative neoplasms: A unifying mechanism of disease pathogenesis and therapeutic targeting.
The Philadelphia chromosome negative myeloproliferative neoplasms (MPNs), essential thrombocythemia, polycythemia vera, and primary myelofibrosis, are clonal hematopoietic stem cell disorders unified by constitutive thrombopoietin receptor (MPL) signaling. All 3 MPN driver mutations, JAK2, CALR, and MPL, converge on enhanced MPL signaling, establishing the thrombopoietin (TPO)/MPL axis as the central molecular hub linking clonal hematopoiesis to the cardinal manifestations of MPN, including thrombosis, hemorrhage, and fibrotic progression. As the principal regulator of hematopoietic stem cell maintenance and megakaryopoiesis and a key mediator of platelet priming, the TPO/MPL axis links stem cell biology to thromboinflammation and disease progression. This review summarizes the physiologic functions of the TPO/MPL axis, its dysregulation in MPN, and the downstream mechanisms linking aberrant MPL signaling to thrombosis, hemorrhage, and fibrotic progression. We further highlight recent advances in our understanding of TPO/MPL signaling in platelet biology, including its roles in platelet activation, metabolism, and thromboinflammation, and discuss emerging therapeutic strategies targeting the TPO/MPL pathway with the goal of simultaneously reducing thrombohemorrhagic complications, limiting fibrotic progression, and diminishing the malignant stem cell clone.
2026-08-03 | Profile of Philadelphia Chromosome Negative (Ph-) Myeloproliferative Neoplasm with Special Emphasis on Vascular Thrombotic Events and the Response to Cytoreductive Therapy in Polycythemia Vera and Essential Thrombocythemia Patients: A Single Center Study from Kerala.
Thrombotic events are a major morbidity among Philadelphia chromosome-negative myeloproliferative neoplasm (Ph-MPN) patients. There is a lack of data from Kerala regarding the profile of Ph-MPN and the prevalence of thrombosis among these patients. To study the clinical profile, driver mutations, incidence of thrombotic events among Ph-MPN patients, and the response to hydroxyurea therapy. We reviewed the medical records of 84 Ph-MPN patients who were on follow-up from April 2019 to June 2023 in a tertiary care hospital in Kerala. There were 48 polycythemia vera (PV), 16 essential thrombocythemia (ET), 14 primary myelofibrosis (PMF), and six unclassifiable MPN (MPN-u) patients. The incidence of Janus kinase 2 (JAK2) mutation was 96, 62.5, and 79% among PV, ET, and PMF patients, respectively. The incidence of calreticulin (CALR) mutation was 37.5 and 21% among ET and PMF patients, respectively. The incidence of thrombotic events was 23/48 (48%), 7/16 (43.5%), and 6/14 (42.8%) among PV, ET, and PMF patients, respectively. All ET and PMF patients with thrombotic events were JAK2V617F-mutated. Eighty-seven percent of the evaluable patients on hydroxyurea for PV achieved freedom from therapeutic phlebotomies. ET patients who were on hydroxyurea achieved a median platelet count of 4.3 lakhs/µL (3.16-6.08). There is a higher incidence of thrombosis among Ph-MPN patients from Kerala, which needs to be ascertained in a population-based study. JAK2V617F mutation is the major determinant of thrombotic episodes in ET and PMF. Hydroxyurea is an effective cytoreductive therapy in PV and ET.
2026-07-21 | Practical Guide for Managing Philadelphia-Negative Myeloproliferative Neoplasms in Patients with Organ Dysfunction.
Classical Philadelphia-negative myeloproliferative neoplasms (MPNs), including polycythaemia vera, essential thrombocythaemia, and myelofibrosis, frequently occur in patients with renal, hepatic, cardiovascular, or hematologic comorbidities. These vulnerabilities complicate treatment selection, dose adjustment, and toxicity monitoring. However, patients with advanced kidney disease, dialysis dependence, decompensated cirrhosis, severe cytopenias, or overlapping organ impairment are often underrepresented in prospective trials. This narrative review presents a practical, organ-adapted framework for selecting MPN therapy in clinically complex patients. We define renal and hepatic impairment, compare commonly used cytoreductive and targeted therapies-including hydroxyurea, busulfan, anagrelide, ruxolitinib, fedratinib, momelotinib, pacritinib, ropeginterferon alfa-2b, and pegylated interferon alfa-2a-and discuss their use in dialysis, decompensated liver disease, cytopenic myelofibrosis, anemia-dominant myelofibrosis, and combined organ vulnerability. The proposed approach prioritizes label-based dose modification when available, cautious dose initiation when evidence is extrapolated, structured early monitoring, and multidisciplinary review for high-risk patients. Management of Philadelphia-negative myeloproliferative neoplasms (MPNs) in organ dysfunction should be individualized according to disease phenotype, treatment goal, organ reserve, hematologic tolerance, frailty, and label-specific safety restrictions. In renal impairment, hydroxyurea and ruxolitinib may remain feasible in selected patients when dose-adjusted and monitored closely, whereas dialysis and severe renal impairment require conservative initiation and multidisciplinary review because direct evidence remains limited. In myelofibrosis, JAK inhibitor choice should be phenotype-adapted: ruxolitinib remains a common standard when blood counts and organ function permit, momelotinib is attractive in anemia-dominant disease, pacritinib is particularly relevant in severe thrombocytopenia, and fedratinib is useful in selected settings but requires thiamine-focused safety management. In hepatic dysfunction or overlapping organ vulnerability, therapy should prioritize safety, reversible contributors, conservative starting strategies, explicit stopping rules, and early reassessment.
2026-07-16 | Successful Topical Treatment of Hydroxyurea-Induced Ulcers Without Drug Discontinuation: A Case Report.
Hydroxyurea, an antineoplastic agent, is widely used to treat essential thrombocythemia and polycythemia vera. Although hydroxyurea-induced skin ulcers are uncommon, they are a recognized long-term adverse effect. Current management generally recommends discontinuation of hydroxyurea as the mainstay of treatment; however, drug withdrawal may aggravate the underlying hematologic disease. We report a case of bilateral medial malleolar ulcers associated with hydroxyurea therapy in a 65-year-old man with essential thrombocythemia, who showed marked improvement after two months of topical treatment with recombinant bovine basic fibroblast growth factor (rb-bFGF) gel, without discontinuation of hydroxyurea. Complete healing was confirmed at 25-month follow-up, while hematologic disease control was maintained. This case suggests that localized wound care with topical rb-bFGF may represent a feasible therapeutic option in selected patients when hydroxyurea discontinuation is not feasible.
2026-08-13 | Hematological trajectories and pregnancy complications in essential thrombocythemia and polycythemia vera
Abstract Women with essential thrombocythemia (ET) and polycythemia vera (PV) are at increased risk of pregnancy complications. During pregnancy, hematologic parameters tend to approach normal values, and previous studies have reported that a greater decline in platelet counts in ET is associated with reduced risk of complications. In this study, we examined longitudinal trajectories of platelet count, hemoglobin, hematocrit, and leukocyte count during pregnancy, characterized pregnancy outcomes, and investigated the association between platelet trajectories and preeclampsia. We established a longitudinal cohort of pregnant women with ET and PV in the Capital Region and Region Zealand between 2010 and 2024, using data from regional laboratory information systems and Danish health registries. In total, 41 ET and 5 PV pregnancies in 35 women were included. The mean age at MPN diagnosis was 30.1 years in women with ET and 34.1 years in women with PV. In ET pregnancies, platelet counts, hemoglobin, hematocrit and leukocyte count changed by − 44%, − 5%, − 12% and + 55%, respectively, from baseline to delivery, and in PV pregnancies − 36%, − 26%, − 25% and + 47%, respectively. Overall, 29% of ET pregnancies had a maternal complication, with preeclampsia being the most common (12%). ET women who developed preeclampsia had significantly higher platelet counts before pregnancy and experienced a greater decline in platelet counts during pregnancy than women without preeclampsia. Thus, hematologic trajectories during pregnancy may help identify women at increased risk of preeclampsia.
2026-08-09 | The thrombopoietin receptor in myeloproliferative neoplasms: A unifying mechanism of disease pathogenesis and therapeutic targeting.
The Philadelphia chromosome negative myeloproliferative neoplasms (MPNs), essential thrombocythemia, polycythemia vera, and primary myelofibrosis, are clonal hematopoietic stem cell disorders unified by constitutive thrombopoietin receptor (MPL) signaling. All 3 MPN driver mutations, JAK2, CALR, and MPL, converge on enhanced MPL signaling, establishing the thrombopoietin (TPO)/MPL axis as the central molecular hub linking clonal hematopoiesis to the cardinal manifestations of MPN, including thrombosis, hemorrhage, and fibrotic progression. As the principal regulator of hematopoietic stem cell maintenance and megakaryopoiesis and a key mediator of platelet priming, the TPO/MPL axis links stem cell biology to thromboinflammation and disease progression. This review summarizes the physiologic functions of the TPO/MPL axis, its dysregulation in MPN, and the downstream mechanisms linking aberrant MPL signaling to thrombosis, hemorrhage, and fibrotic progression. We further highlight recent advances in our understanding of TPO/MPL signaling in platelet biology, including its roles in platelet activation, metabolism, and thromboinflammation, and discuss emerging therapeutic strategies targeting the TPO/MPL pathway with the goal of simultaneously reducing thrombohemorrhagic complications, limiting fibrotic progression, and diminishing the malignant stem cell clone.
2026-08-03 | Profile of Philadelphia Chromosome Negative (Ph-) Myeloproliferative Neoplasm with Special Emphasis on Vascular Thrombotic Events and the Response to Cytoreductive Therapy in Polycythemia Vera and Essential Thrombocythemia Patients: A Single Center Study from Kerala.
Thrombotic events are a major morbidity among Philadelphia chromosome-negative myeloproliferative neoplasm (Ph-MPN) patients. There is a lack of data from Kerala regarding the profile of Ph-MPN and the prevalence of thrombosis among these patients. To study the clinical profile, driver mutations, incidence of thrombotic events among Ph-MPN patients, and the response to hydroxyurea therapy. We reviewed the medical records of 84 Ph-MPN patients who were on follow-up from April 2019 to June 2023 in a tertiary care hospital in Kerala. There were 48 polycythemia vera (PV), 16 essential thrombocythemia (ET), 14 primary myelofibrosis (PMF), and six unclassifiable MPN (MPN-u) patients. The incidence of Janus kinase 2 (JAK2) mutation was 96, 62.5, and 79% among PV, ET, and PMF patients, respectively. The incidence of calreticulin (CALR) mutation was 37.5 and 21% among ET and PMF patients, respectively. The incidence of thrombotic events was 23/48 (48%), 7/16 (43.5%), and 6/14 (42.8%) among PV, ET, and PMF patients, respectively. All ET and PMF patients with thrombotic events were JAK2V617F-mutated. Eighty-seven percent of the evaluable patients on hydroxyurea for PV achieved freedom from therapeutic phlebotomies. ET patients who were on hydroxyurea achieved a median platelet count of 4.3 lakhs/µL (3.16-6.08). There is a higher incidence of thrombosis among Ph-MPN patients from Kerala, which needs to be ascertained in a population-based study. JAK2V617F mutation is the major determinant of thrombotic episodes in ET and PMF. Hydroxyurea is an effective cytoreductive therapy in PV and ET.
2026-07-21 | Practical Guide for Managing Philadelphia-Negative Myeloproliferative Neoplasms in Patients with Organ Dysfunction.
Classical Philadelphia-negative myeloproliferative neoplasms (MPNs), including polycythaemia vera, essential thrombocythaemia, and myelofibrosis, frequently occur in patients with renal, hepatic, cardiovascular, or hematologic comorbidities. These vulnerabilities complicate treatment selection, dose adjustment, and toxicity monitoring. However, patients with advanced kidney disease, dialysis dependence, decompensated cirrhosis, severe cytopenias, or overlapping organ impairment are often underrepresented in prospective trials. This narrative review presents a practical, organ-adapted framework for selecting MPN therapy in clinically complex patients. We define renal and hepatic impairment, compare commonly used cytoreductive and targeted therapies-including hydroxyurea, busulfan, anagrelide, ruxolitinib, fedratinib, momelotinib, pacritinib, ropeginterferon alfa-2b, and pegylated interferon alfa-2a-and discuss their use in dialysis, decompensated liver disease, cytopenic myelofibrosis, anemia-dominant myelofibrosis, and combined organ vulnerability. The proposed approach prioritizes label-based dose modification when available, cautious dose initiation when evidence is extrapolated, structured early monitoring, and multidisciplinary review for high-risk patients. Management of Philadelphia-negative myeloproliferative neoplasms (MPNs) in organ dysfunction should be individualized according to disease phenotype, treatment goal, organ reserve, hematologic tolerance, frailty, and label-specific safety restrictions. In renal impairment, hydroxyurea and ruxolitinib may remain feasible in selected patients when dose-adjusted and monitored closely, whereas dialysis and severe renal impairment require conservative initiation and multidisciplinary review because direct evidence remains limited. In myelofibrosis, JAK inhibitor choice should be phenotype-adapted: ruxolitinib remains a common standard when blood counts and organ function permit, momelotinib is attractive in anemia-dominant disease, pacritinib is particularly relevant in severe thrombocytopenia, and fedratinib is useful in selected settings but requires thiamine-focused safety management. In hepatic dysfunction or overlapping organ vulnerability, therapy should prioritize safety, reversible contributors, conservative starting strategies, explicit stopping rules, and early reassessment.
2026-07-16 | Successful Topical Treatment of Hydroxyurea-Induced Ulcers Without Drug Discontinuation: A Case Report.
Hydroxyurea, an antineoplastic agent, is widely used to treat essential thrombocythemia and polycythemia vera. Although hydroxyurea-induced skin ulcers are uncommon, they are a recognized long-term adverse effect. Current management generally recommends discontinuation of hydroxyurea as the mainstay of treatment; however, drug withdrawal may aggravate the underlying hematologic disease. We report a case of bilateral medial malleolar ulcers associated with hydroxyurea therapy in a 65-year-old man with essential thrombocythemia, who showed marked improvement after two months of topical treatment with recombinant bovine basic fibroblast growth factor (rb-bFGF) gel, without discontinuation of hydroxyurea. Complete healing was confirmed at 25-month follow-up, while hematologic disease control was maintained. This case suggests that localized wound care with topical rb-bFGF may represent a feasible therapeutic option in selected patients when hydroxyurea discontinuation is not feasible.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
11 orphan drug designations for Essential thrombocythemia, including 1 approved therapy.
11 orphan drug designations for Essential thrombocythemia, including 1 approved therapy.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
recombinant fully human IgG1 monoclonal antibody selectively targeting PD-L2 | antibodies | FDA | 2026-01-01 | — | mAbTree Biologics AG |
peginterferon alfa-2a | proteins | FDA | 2024-06-27 | — | Pharma& U.S. Inc. |
Ropeginterferon alfa-2b | proteins | EMA | 2022-10-11 | — | Aop Orphan Pharmaceuticals GmbH |
Hetrombopag olamine, Rafutrombopag | — | FDA | 2022-06-13 | — | Jiangsu Hengrui Pharmaceuticals Co., Ltd. |
Bomedemstat ditosilate | small molecules | EMA | 2021-06-21 | — | Merck Sharp & Dohme B.V. |
bomedemstat | small molecules | FDA | 2018-11-07 | — | Merck & Co., Inc. |
pegylated proline interferon alpha-2b | proteins | FDA | 2014-04-11 | — | PharmaEssentia |
Pomalidomide | — | EMA | 2010-07-27 | — | Celgene Europe Limited |
ruxolitinib phosphate | small molecules | FDA | 2010-03-22 | — | Incyte Corporation |
Anagrelide hydrochloride monohydrate [Xagrid] | small molecules | EMA | 2000-12-29 | — | [INACTIVE] Shire Pharmaceutical Development Limited |
Anagrelide [Agrylin] | small molecules | FDA | 1988-01-27 | 1997-03-14 | Takeda Development Center Americas, Inc. |
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