DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for thrombocytosis disease — screening already-approved drugs against its 14-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleThrombocytosis disease maps to a 14-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for thrombocytosis disease is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
U2 small nuclear RNA auxiliary factor 1 (U2AF1) — U2AF1 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet hezdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1JMT · 2.2 Å · ligand HEXANE-1,6-DIOL (HEZ). Experimental structure, not a prediction.
What the evidence adds up to
In a prospective study of 777 adults with platelet counts above 500 x 10⁹/L, infection accounted for 21.9% of cases, rebound thrombocytosis for 19.4%, tissue damage for 17.9%, chronic inflammatory disorders for 13.1%, and malignancy for 5.9%; 6.1% had multiple simultaneous causes. A retrospective review of 801 cases found secondary thrombocytosis more common than primary, with infectious causes responsible for nearly half of all cases; patients with infection-related thrombocytosis had faster platelet normalisation but a higher risk of death than those with secondary non-infectious causes. Extreme thrombocytosis, defined as counts above 1 million x 10⁹/L, was most frequent in patients with multiple aetiological factors, myeloproliferative disorders, or after splenectomy.
Essential thrombocythaemia is the most common primary cause, and patients with it are more likely to have extreme (>800 x 10⁹/L) and prolonged (>1 month) thrombocytosis. In children, essential thrombocythaemia is roughly 100-fold rarer than in adults, and clonal markers are found in only 25.8% of paediatric cases compared with 80–90% in adults; the 2015 study investigated JAK2 V617F, MPL, and CALR mutations in a large paediatric cohort but reported no additional mutations. A 2004 report described three cases of familial thrombocytosis across three generations with elevated serum thrombopoietin levels but no mutations in the TPO gene or the transmembrane domain of c-MPL, suggesting altered TPO gene regulation rather than a coding mutation.
In 203 patients with non-metastatic nasopharyngeal carcinoma treated with intensity-modulated radiotherapy, 20.7% had thrombocytosis before treatment and 39.9% developed it during therapy; those with thrombocytosis had more advanced N stage (48.8% vs 30.0%, P = 0.008) and significantly lower 5-year progression-free survival (78.3% vs 89.1%, P = 0.019). Multivariate analysis identified thrombocytosis as an independent predictor of inferior progression-free survival (hazard ratio 2.37, 95% CI 1.08–5.21, P = 0.032), with a similar result in patients receiving induction chemotherapy with a TP regimen (HR 2.88, 95% CI 1.12–7.36, P = 0.028). A 2023 case report of a traumatic amputee with reactive thrombocytosis noted that secondary thrombocytosis resolves when the underlying event is managed, but extreme thrombocytosis may lead to thromboembolic episodes such as mesenteric vein thrombosis, pulmonary embolism, and acute myocardial infarction.
The distinction between reactive and clonal thrombocytosis is clinically important because it affects assessment, prognosis, and treatment; myeloproliferative neoplasms carry a distinctly elevated risk of thrombosis that drives treatment decisions. No drug is evaluated in these abstracts, and no targeted therapy is tested in a clinical trial. What remains missing is prospective validation of thrombocytosis as a prognostic marker in nasopharyngeal carcinoma, molecular markers to distinguish clonal from reactive thrombocytosis in children, and clinical trial data on new therapeutic targets for thrombocytosis.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Internal Medicine · 1991 · 86 citations
Thrombocytosis in adults: analysis of 777 patients
AbstractA total of 777 patients with thrombocytosis, defined as a platelet count of greater than 500 x 10(9)l-1, seen in a University hospital over a 1-year period, were studied prospectively for aetiology. The most frequent causes of thrombocytosis were infection (21.9%), rebound thrombocytosis (19.4%), tissue damage (17.9%), chronic inflammatory disorders (13.1%) and malignancy (5.9%). Thrombocytosis associated with multiple causative factors, occurring simultaneously, was seen in 6.1% of cases. Thrombocytosis of greater than or equal to 1 million x 10(9)l-1 was found most frequently in patients with multiple aetiological factors occurring at the same time, in myeloproliferative disorders, or in postsplenectomy patients.
Journal of Clinical Medicine Research · 2012 · 59 citations · open access
Etiology of Thrombocytosis in a General Medicine Population: Analysis of 801 Cases With Emphasis on Infectious Causes
AbstractBACKGROUND: The clinical importance of an elevated platelet count is often overlooked, particularly as a diagnostic clue to the presence of an underlying infection. We sought to better describe the relationship between thrombocytosis and inflammatory conditions, with a focus on infectious causes. METHODS: We retrospectively reviewed 801 sequential cases of thrombocytosis (platelet count > 500 × 10(9)/L) at a tertiary care hospital. RESULTS: Essential thrombocythemia was the most common cause of primary thrombocytosis, and these patients were more likely to have extreme (> 800 × 10(9)/L) and prolonged (> 1 month) thrombocytosis. Secondary thrombocytosis was more common than primary, with infectious causes accounting for nearly half the cases. Demographic factors associated with an infectious etiology included inpatient status, quadriplegia/paraplegia, an indwelling prosthesis, dementia and diabetes. Clinical and laboratory characteristics associated with an infectious cause of thrombocytosis included fever, tachycardia, weight loss, hypoalbuminemia, neutrophilia, leukocytosis and anemia. Patients with thrombocytosis secondary to infection had a more rapid normalization of platelet count, but higher risk of dying, than those with secondary, non-infectious causes. CONCLUSIONS: Infection is a common cause of thrombocytosis and should be considered in patients with comorbidities that increase risk of infection and when clinical and/or laboratory data support an infectious etiology. Thrombocytosis may have prognostic implications as a clinical parameter.
British Journal of Haematology · 2015 · 23 citations · open access
How we diagnose and treat essential thrombocythaemia
AbstractThe approach to the diagnosis and management of essential thrombocythaemia (ET) is steadily changing, influenced by advances in molecular biology, data from clinical trials and retrospective analyses of patient cohorts. In the past decade options for clinical management largely remain unchanged, but who we treat, and with what target in mind, is evolving. A further area of change is recognition of symptoms that may be associated with ET, as well as other myeloproliferative neoplasms, and that potential options for their management are becoming available. Judicious and careful diagnosis is increasingly a fundamental key to successful management followed by cytoreductive therapy in a subset of patients. In this review we demonstrate our management strategies for ET using a case-based format.
Distinct molecular abnormalities underlie unique clinical features of essential thrombocythemia in children
AbstractEssential thrombocythemia (ET) is rare in children, with an annual incidence of ~100-fold lower than that in adults. 1 The rarity of the disease in children makes the clinical course and pathogenesis of childhood ET far less clear. It is reported that clonal markers are much less common in children with ET (25.8%) than that in adult cases (80–90%). 2 , 3 , 4 Except for JAK2 V617F, and MPL and calreticulin ( CALR ) mutations, no other mutations have yet been reported in childhood ET. 2 , 5 , 6 , 7 , 8 More molecular markers are needed to distinguish clonal from reactive thrombocytosis in children. The present study investigated the JAK2 V617F, and MPL and CALR mutations in a large cohort of children with ET. We conducted the first study to analyze the molecular profiles by targeted next-generation sequencing and to investigate the JAK2 46/1 haplotype in childhood ET.
American Journal of Hematology · 2004 · 18 citations · open access
A case of familial thrombocytosis: Possible role of altered thrombopoietin production
AbstractFamilial thrombocytosis (FT) is an inherited disorder with clinical presentations similar to essential thrombocytosis (ET). In several pedigrees, overproduction of thrombopoietin (TPO) has been shown to be responsible for the disease. We report herein three cases of thrombocytosis in three successive generations. All cases had increased serum TPO levels. Sequence analysis of TPO gene and transmembrane domain of c-MPL, known as the TPO receptor, revealed no mutations. Platelet c-MPL expression was similar or slightly increased as compared to normal volunteers. These data suggest that altered regulation of the TPO gene might be involved in the pathogenesis of FT.
International Journal of Research in Medical Sciences · 2023 · 1 citations · open access
Extreme thrombocytosis in traumatic amputee and role of thromboembolism prophylaxis: a case report
AbstractPlatelets are the smallest blood component produced in the bone marrow that plays a fundamental role in the blood clotting process. A normal platelet count applicable to all adults is 150 to 400×109/l. Thrombocytosis develops when the platelet count exceeds 450×109/l. Thrombocytosis is classified into primary thrombocytosis and secondary (or extreme) thrombocytosis. Primary thrombocytosis is a chronic myeloproliferative disorder in which sustained megakaryocyte proliferation leads to an increase in the number of circulating platelets. Extreme thrombocytosis or reactive thrombocytosis, is defined as abnormally high platelet count in the absence of chronic myeloproliferative disease, secondary to an underlying events, disease, or the use of certain medications. Causes of reactive thrombocytosis include acute blood loss, acute infection, amputation, iron deficiency, asplenia, cancer, chronic inflammatory or infectious diseases. Secondary thrombocytosis resolves when the underlying event is managed. Extreme thrombocytosis may result in thromboembolic episode such as mesenteric vein thrombosis, pulmonary embolism and acute myocardial infarction. In patients who survive after trauma the platelet count displays a bimodal response with an initial decrease below baseline values, followed by an increase above the normal range after 1 week. We report a similar experience of a trauma patient with reactive thrombocytosis and discussion on importance of thromboprophylaxis.
Prognostic value of thrombocytosis in nasopharyngeal carcinoma in the era of intensity-modulated radiotherapy
AbstractINTRODUCTION: Thrombocytosis, recognized as a clinically significant event, has been established as an unfavorable prognostic factor in various solid tumors. This study aimed to investigate the prognostic value of thrombocytosis-occurring either before or during treatment-in patients with non-metastatic nasopharyngeal carcinoma (NPC) who received intensity-modulated radiotherapy (IMRT). METHODS: A total of 203 patients with NPC who received IMRT were retrospectively analyzed. Thrombocytosis was defined as a platelet count exceeding 300 × 10⁹/L. The prognostic significance of thrombocytosis was assessed using the log-rank test and multivariate analyses. RESULTS: Among the 203 patients, 42 cases (20.7%) exhibited thrombocytosis prior to treatment initiation, and 81 cases (39.9%) developed thrombocytosis during therapy. Patients with thrombocytosis had more advanced N stage compared to those without (48.8% vs. 30.0%; P = 0.008). The 5-year progression-free survival (PFS) rate was significantly lower in patients with thrombocytosis than in those without (78.3% vs. 89.1%; P = 0.019). Multivariate analyses revealed that thrombocytosis was an independent prognostic factor for inferior PFS (hazard ratio [HR] = 2.37, 95% confidence interval [CI] = 1.08-5.21; P = 0.032). A similar result was observed in the subgroup of patients who received induction chemotherapy with the TP regimen (HR = 2.88, 95% CI = 1.12-7.36; P = 0.028). CONCLUSIONS: Thrombocytosis occurring before or during treatment serves as a valuable predictor of disease progression and poor prognosis in patients with NPC. Patients presenting with thrombocytosis may require more intensive therapeutic strategies; therefore, the presence of thrombocytosis should be considered when selecting an induction chemotherapy regimen. Further prospective studies are warranted to confirm these findings.
AbstractThrombocytosis is a clinical condition that is frequently seen, with a high percentage of instances being found by chance.The diagnosis of thrombocytosis might be difficult due to the wide range of possible diagnoses.Thrombocytosis may be fake, the result of a reaction, or the result of a clonal problem.This distinction is significant because it has effects on assessment, prognosis, and treatment.The myeloproliferative neoplasms, particularly essential thrombocythemia and polycythemia vera, are linked with clonal thrombocytosis, which has a distinct prognosis profile and a significantly elevated risk of thrombosis.The motivation behind these illnesses' treatment plans is this risk.New therapeutic targets are awaiting investigation in clinical studies using targeted treatments for thrombocytosis.[1
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works using Disease Ontology synonyms, resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
