DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for platelet-type bleeding disorder 9 — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePlatelet-type bleeding disorder 9 maps to a 1-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 platelet-type bleeding disorder 9 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
integrin subunit alpha 2 (ITGA2) — ITGA2 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 2sdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9RIE · 1.305 Å · ligand (2S)-2-hydroxybutanedioic acid (LMR). Experimental structure, not a prediction.
What the evidence adds up to
In a 2007 review of immune thrombocytopenic purpura in adults, splenectomy is described as the best curative treatment for chronic disease after at least six months of follow-up. Other treatments such as anti-D, rituximab, or dexamethasone may allow splenectomy to be postponed if a haemostatic platelet count is reached. Mortality from bleeding may be relevant only in patients refractory to splenectomy. The review states that an aggressive therapeutic approach is justified only in patients with platelet counts below 20 x 10⁹/L and those refractory to splenectomy.
A 2010 summary on inherited disorders of platelet function notes that Glanzmann thrombasthenia, a rare autosomal recessive disorder caused by defect or deficiency in platelet integrin αIIbβ3, results in absent platelet aggregation and a significant clinical bleeding diathesis. The summary states that present diagnostic testing for platelet function disorders and von Willebrand’s Disease often fails to identify the cause of bleeding in individuals with inherited mucocutaneous bleeding disorders.
A 2017 observational cohort study nested in a previous multicentre randomised thromboprophylaxis trial evaluated the association between platelet transfusions and major bleeding in 2,256 critically ill patients with thrombocytopenia. Among these, 71 patients (3.1%) received 190 platelet transfusions; 121 of those transfusions (63.7%) were given to 54 non-bleeding, thrombocytopenic patients. Adjusted rates of major bleeding were not statistically different with or without platelet transfusions (hazard ratio 0.85; 95% confidence interval 0.42–1.72). No significant association was found between platelet transfusion and thrombosis or death in the intensive care unit in adjusted analyses. The median post-transfusion platelet count increment was 20 x 10⁹/L at 3.5 hours. The authors note that inferences were limited by the small number of transfused patients and that clinical trials are needed.
A 2009 review of new antiplatelet agents discusses five categories under clinical study: thienopyridines, cyclopentyltriazolopyrimidines, anti-von Willebrand factor aptamers, thrombin receptor antagonists, and thromboxane receptor antagonists. The review states that each therapy aims to improve clinical response with hopes of incremental efficacy and decreased bleeding complications. No data from the abstracts directly address platelet-type bleeding disorder 9. What is still missing is any clinical trial specifically designed for this rare disorder, adequate patient stratification by molecular defect, and funding to move beyond expert-opinion-based guidelines.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Hematology · 2007 · 86 citations
Immune thrombocytopenic purpura in adults
AbstractPURPOSE OF REVIEW: A review of recent studies was conducted to determine if guidelines promulgated by the American Society of Hematology and the British Committee for Standards in Haematology need to be updated as these were based mainly on expert opinion rather than outcomes derived from clinical trials. RECENT FINDINGS: Recent studies suggest that most patients with immune thrombocytopenic purpura have a disease that is generally well tolerated, with little morbidity. Splenectomy remains the best 'curative' treatment for adults with chronic disease (at least 6 months of follow up). Other treatments such as anti-D, rituximab or dexamethasone may allow the decision of splenectomy to be postponed, possibly indefinitely, if hemostatic platelet count is attained. Mortality from bleeding may be relevant only in patients refractory to splenectomy. Cytotoxic agents should be reserved for patients with bleeding refractory to other treatments. SUMMARY: Patients with platelet counts less than 30 x 10(9)/l or bleeding have to be treated but management decisions should also be based on lifestyle, age, and other medical conditions that may contribute to the risk of serious bleeding. An aggressive therapeutic approach is justified only in patients with platelet counts below 20 x 10(9)/l and those refractory to splenectomy. Newer therapies may be more targeted in their action.
Inherited disorders of platelet function and challenges to diagnosis of mucocutaneous bleeding
AbstractSUMMARY: Platelets play a pivotal role in the arrest of bleeding at sites of vascular injury. Following endothelial damage, they respond rapidly by adhesion to subendothelial matrix proteins resulting in platelet activation, spreading, aggregation, secretion and recruitment of additional platelets to form the primary haemostatic plug. This mass provides a surface for thrombin generation and fibrin mesh formation that stabilizes the clot. Careful study of patients with inherited platelet disorders and, subsequently, of informative animal models, has identified structural platelet abnormalities that have enhanced our understanding of platelet function. The investigations of rare, but severe, inherited platelet disorders have led us to the discovery of causative molecular defects. One of the most informative is the rare autosomal recessive disorder Glanzmann thrombasthenia, caused by defect or deficiency in the platelet integrin alphaIIbbeta3, resulting in absent platelet aggregation and a significant clinical bleeding diathesis. Our new challenge is to understand the mechanisms underlying more common, but less well-defined, mucocutaneous bleeding (MCB) disorders. Present diagnostic testing for platelet function disorders and von Willebrand's Disease often fails to identify the cause of bleeding in individuals with inherited MCB.
Research and Practice in Thrombosis and Haemostasis · 2017 · 14 citations · open access
The association between platelet transfusions and bleeding in critically ill patients with thrombocytopenia
AbstractBackground Platelet transfusions are commonly used to treat critically ill patients with thrombocytopenia. Whether platelet transfusions are associated with a reduction in the risk of major bleeding is unknown. Patients/Methods Observational cohort study nested in a previous multicenter, randomized thromboprophylaxis trial in the intensive care unit (ICU). The objective was to evaluate the association between platelet transfusions and adjudicated major bleeding events. Platelet transfusion episodes were reviewed for timing of administration, product type, and dose. Major bleeding with and without platelet transfusions was adjusted for severity of thrombocytopenia, use of anti‐platelet agents, surgery and other covariates. Secondary outcomes were thrombosis, death in ICU and platelet count increment. Results Among 2,256 patients, 71 (3.1%) received 190 platelet transfusions. Of those, 121 (63.7%) were administered to 54 non‐bleeding, thrombocytopenic patients. Adjusted rates of major bleeding were not statistically different with or without the administration of platelet transfusions (hazard ratio for transfused patients 0.85; 95% confidence interval, 0.42‐1.72). We did not find a significant association between platelet transfusion use and thrombosis or death in ICU in adjusted analyses. Thrombocytopenia, anemia, major or minor bleeding and use of anticoagulants were associated with platelet transfusion administration. The median post‐transfusion platelet count increment was 20×10 9 /L at 3.5 hours post‐transfusion. Conclusions Rates of major bleeding were not different for patients who did and did not receive platelet transfusions. Inferences were limited by the small number of transfused patients. Clinical trials are needed to better investigate the potential hemostatic benefit and potential harms of platelet transfusions for this high‐risk population.
Current Opinion in Cardiology · 2009 · 10 citations
A new generation of antiplatelet agents
AbstractPURPOSE OF REVIEW: Since the development and market entry of clopidogrel, a platelet ADP blocker, physicians have had few new antiplatelet options available to them for the treatment of acute and chronic coronary disease, specifically in the setting of acute coronary syndromes, percutaneous coronary intervention, and chronic stent management. Over the years, limitations of current antiplatelet regimens have emerged, establishing a need for novel antiplatelet drugs. This article discusses potential new targets for platelet inhibition and reviews innovative antiplatelet therapies under investigation. RECENT FINDINGS: There are five main categories of antiplatelet therapies currently undergoing clinical study, consisting of the thienopyridines (P2Y12 receptor antagonists), cyclopentyltriazolopyrimidines (P2Y12 receptor antagonists), anti-von Willebrand factor aptamers, thrombin receptor (protease-activated receptor-1) antagonists, and thromboxane receptor antagonists. Early studies of these agents are discussed. SUMMARY: Each of these new antiplatelet therapies has a unique profile that is aimed at improving clinical response with hopes of incremental efficacy and decreased complications, specifically bleeding.
Effects of 3‐Azidothymidine on Platelet Counts, Indium‐111‐Labelled Platelet Kinetics, and Antiplatelet Antibodies
AbstractTreatment of the acquired immunodeficiency syndrome with 3-azidothymidine (zidovudine; AZT) can induce severe neutropenia and anemia, while platelet counts increase. In order to understand the mechanism by which this favorable effect on platelets is induced, we prospectively studied platelet kinetics and platelet serology in 8 hemophiliacs receiving the drug. All patients underwent a second investigation after 3 months of treatment. Four patients were thrombocytopenic before treatment. Platelet counts increased significantly already after 1 week of treatment (p = 0.03), when only 3 patients remained thrombocytopenic. In these latter patients a further increase of platelet counts was noticed during the following 3 months. Platelet life-span was shortened in all patients at the initial investigation and a significant prolongation was measurable at the second evaluation (p = 0.015). Platelet-associated immunoglobulin G was increased in 3 patients at the first investigation and in 4 patients at the follow-up. Platelet-associated complement (PAC3d) was elevated in all subjects at the first determination. It decreased in 6, but increased in 2 patients thereafter; thus these changes did not become significant (p = 0.078). Immunofluorescence studies revealed antiplatelet antibodies in 7 patients' sera before treatment, and in 5 sera during drug therapy. At both investigations, the antibodies bound to the platelet glycoprotein IIIa as was demonstrated by immunoprecipitation of radiolabeled platelet proteins. We conclude, that AZT treatment improves platelet counts in HIV-infected hemophiliacs primarily by a prolongation of platelet survival without having a significant influence on antiplatelet antibody binding.
Scandinavian Journal of Haematology · 1983 · 9 citations
An Assessment of the Sensitivity of 3 Bleeding Time Techniques
AbstractThe sensitivity of 3 bleeding time techniques to an aspirin-induced defect of platelet function has been assessed in 35 normal volunteers. A carefully standardised Ivy technique was compared with 2 commercial devices for a template bleeding time, the Simplate II and the Thrombolette. The standardised Ivy and the Simplate II were found to have a similar sensitivity; the Thrombolette tended to be less sensitive but the difference was not significant.
Cambridge University Press eBooks · 2001 · 1 citations
Clinical approach to the bleeding patient
AbstractINTRODUCTION Reduced platelet count or function is typically expressed clinically as a bleeding problem; further chapters of this book discuss platelet disorders in more detail. The clinician faced with a patient presenting hemorrhagic symptoms, however, must consider a much broader differential diagnosis than just a platelet problem. The present chapter describes a systematic approach to such a bleeding patient. This involves taking initial urgent measures if required and then performing a brief inspection for subcutaneous bleeding, taking a focused medical history, completing the physical examination, and reviewing the initial laboratory tests. INITIAL URGENT MEASURES If the patient is actively bleeding at the moment of presentation, it may be necessary to estimate the extent of blood loss; in the acute phase of hemorrhage, the hemoglobin level will be uninformative; (postural) hypotension or tachycardia are signs of a filling defect of the circulation and the need for fluid replacement. In an actively bleeding patient, it is always appropriate to place a peripheral venous line at the moment of drawing blood. If there is suspicion of an important hemostatic defect, one should avoid puncture of a neck vein or of an artery, since catastrophic hemorrhage can be the consequence, resulting in compression of the airways in the neck (Fig. 9.1) or of the femoral nerve in the groin following arterial blood sampling.
Hereditary αδ-Storage Pool Deficiency with the Abnormal Structures of the Platelet Microtubules.
AbstractAbstract The case is a 27-year-old man, who referred to us presenting the mild bleeding tendency after extraction of a tooth. Bleeding time was 3 minutes by the Duke method, and his platelet count was slightly decreased (7x10 10 /l). His mother also has the similar platelet abnormality. They have no albinism. The peripheral smear demonstrated the abnormal platelet morphology with hypo or agranular and large forms. Almost normal platelets were also present on the smear. A platelet adhesion test showed the impaired collagen adhesion. A platelet aggregation study revealed the abnormally poor responses to adenosine diphosphate, collagen, arachidonate, U-46619, and a relatively retained response to ristocetin. Electron microscopy of the platelets demonstrated 2 populations: one with almost normal distribution of the granules, the other with marked decrease in both α and dense granules, even though the former population had the abnormal granules and the obvious vacuoles in the platelets. Flow cytometry revealed the reduced Mepacrine positive platelets and the decreased surface CD62P induced with phorbor ester in the patient. The patient platelets contained the reduced concentration of both adenosine triphosphate and serotonin, compared with the normal control. The cytoskeleton structures were examined with immunocytochemistry using the specific antibodies. Most platelets of the patient lost the typical coiled marginal bands and showed the yarnball-like structures of the microtubules, although the actin microfilaments were relatively retained. In other words, the platelets even with the almost normal distribution of the granules have a disturbed tubulin organization, which were not apparent in the leukocytes. These results suggested that some platelet-specific proteins, such as β1 tubulin, involved in the formation of the microtubules could be causative for this hereditary storage pool deficiency.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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