DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for platelet-type bleeding disorder 18 — 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 18 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 18 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
RAS guanyl releasing protein 2 (RASGRP2) — RASGRP2 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6AXF · 3.1 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
The abstracts do not describe a disease called "platelet-type bleeding disorder 18." They discuss platelet dysfunction in general, both hereditary and acquired. One 1992 review states that hereditary platelet function defects are generally rare, though hereditary storage pool disease is common enough to be suspected in a child with characteristic findings. The same review notes that acquired platelet function defects, especially those caused by drugs, are very common and should be suspected in patients with easy bruising or mucosal bleeding. The mainstay of therapy for significant bleeding from these defects is liberal infusion of platelet concentrates, and for acquired defects, any offending drugs should be discontinued.
A 2011 review on reversing antiplatelet drug effect states there are no guidelines for management of patients on antiplatelet agents who need urgent surgery or have serious bleeds. The author describes an approach based solely on personal experience and very limited published data. A 2011 study of 46 trauma patients on clopidogrel found that platelet inhibition ranged from 0% to 89% as measured by a point-of-care assay. Only two patients had hemorrhagic complications, and the authors concluded that a large percentage of patients had undetectable or low platelet inhibition despite reportedly being on the drug, making reversal therapies unlikely to be beneficial in that group.
A 2021 study of 49 patients with acute intracranial bleeding found clinically relevant platelet dysfunction in 14 patients (29%). Of those, 8 were on antiaggregatory medication, and 6 patients (12%) were diagnosed with acute acquired platelet dysfunction not due to medication. The authors recommend that treatment algorithms for coagulopathy in this cohort should incorporate aggregometric measures for goal-directed therapy. A 2001 clinical approach chapter describes a systematic evaluation of the bleeding patient, including urgent measures, inspection for subcutaneous bleeding, focused history, physical exam, and initial lab tests.
What is missing is any specific trial of a drug for a condition called platelet-type bleeding disorder 18. The abstracts provide no randomised data on any pharmacologic reversal agent, no validated threshold of platelet inhibition that predicts bleeding, and no prospective trial comparing platelet transfusion versus other therapies in this context. Money for such trials, a standardised diagnostic definition, and patient stratification by mechanism of dysfunction are all absent.
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 Oral Implantology · 2007 · 94 citations
Use of Platelet-Rich Plasma in the Management of Oral Biphosphonate-Associated Osteonecrosis of the Jaw: A Report of 2 Cases
AbstractBisphosphonates (BP) are nonhormonal medications used in the treatment of various bone malignancies and metabolic conditions. Since 2003, there have appeared a significant and growing number of articles in the worldwide medical and dental literature describing the complication of an osteonecrosis of the jaws associated with the intravenous and, most recently, the oral form of BP medication that has been refractory to any definitive form of treatment. The authors have successfully managed 2 patients taking the oral form of BP with adjunctive treatment using platelet-rich plasma (PRP), and in one case with hyperbaric oxygen (HBO). We were able to obtain complete remission in each case, which is defined as resolution of pain and complete closure of exposed bone in the jaws. The purpose of this report is to describe a treatment protocol and the rationale for using PRP and HBO to obtain complete remission of this new pathologic condition.
How do I transfuse platelets (PLTs) to reverse anti‐PLT drug effect? (CME)
AbstractAntiplatelet agents (APAs) are commonly used in clinical practice to either treat or prevent arterial thrombotic disorders in patients at high risk. The newer APAs are more potent with higher bleeding risk profiles. Patients who present with serious bleeds or need urgent surgical interventions while on APAs may require reversal of these agents' effect on PLTs. Currently, there are no guidelines for management of such patients. This article describes my approach to PLT transfusion or use of pharmacologic agents in such clinical scenarios based solely on personal experience and very limited published data.
Seminars in Thrombosis and Hemostasis · 1992 · 38 citations
Platelet Function Defects: A Clinical Review
AbstractPlatelet dysfunction, especially acquired forms, are common causes of hemorrhage, especially in association with trauma and surgery. Although the hereditary platelet function defects are generally quite rare, hereditary storage pool disease is common enough to be suspected in an individual, usually a child, with characteristic historical and clinical findings. The acquired platelet function defects, especially those resulting from drugs, are very common and should promptly be suspected in patients developing easy and spontaneous bruising, mild to moderate mucosal membrane hemorrhage, or unexplained bleeding associated with trauma or surgery. The template bleeding time is generally useful as a screening test of platelet function, but a normal template bleeding time, in the presence of a suggestive history, suggestive clinical findings, or in the patient frankly bleeding, is not reliable and platelet aggregation or lumi-aggregation should be done in appropriate clinical situations. The mainstay of therapy for essentially all these defects, if bleeding is significant, is the liberal infusion of appropriate numbers of platelet concentrates. The acquired platelet function defects, of course, should also be managed by attempts to treat or control the underlying disease, if possible, and offending drugs or potentially offending drugs should promptly be discontinued.
The Journal of Trauma: Injury, Infection, and Critical Care · 2011 · 31 citations
A New Clopidogrel (Plavix) Point-of-Care Assay: Rapid Determination of Antiplatelet Activity in Trauma Patients
AbstractINTRODUCTION: An increasing proportion of trauma patients are on anticoagulation or antiplatelet therapy. Unlike warfarin, where measuring international normalized ratio can help direct management, measuring platelet inhibition from clopidogrel (Plavix) is not standardized. We report the use of a new P2Y12 point-of-care assay (VerifyNow; Accumetrics, San Diego, CA) to determine the magnitude of platelet inhibition in trauma patients using clopidogrel. METHODS: Trauma patients in 2009 were queried for clopidogrel use by prehospital personnel and the trauma team. Blood was obtained on admission for patients reportedly taking clopidogrel and was assayed for platelet inhibition using the VerfiyNow-P2Y12 device that measures P2Y12 reaction units and photometrically determines platelet inhibition percentage within 30 minutes. Patient demographics including age, Injury Severity Score, mechanism of injury, and complications from hemorrhage were also analyzed. RESULTS: In the time studied, 46 patients taking clopidogrel were assayed for platelet inhibition. The mean age was 75.9 years±11.8 years, and the most common mechanism of injury was fall (86.9%). Platelet inhibition ranged from 0% to 89%. There were no deaths, and only two patients, from the 0% and>30% inhibition group, had hemorrhagic complications (increased intracranial hemorrhage). CONCLUSIONS: The P2Y12 point-of-care assay determined that a large percentage of patients had undetectable or low platelet inhibition despite reportedly being on clopidogrel therapy. These patients may be clopidogrel nonresponders or noncompliant. It is unlikely that clopidogrel reversal therapies, such as platelet transfusions or Desmopressin, would be beneficial in this group. Further studies stratifying the percent platelet inhibition needed to increase bleeding complications is warranted to optimize management strategies.
Scandinavian Journal of Haematology · 1981 · 14 citations
Prolonged Bleeding Time with Adequate Platelet Count in Hospital Patients
Abstract100 patients with a modified Ivy bleeding time longer than 10 min in the presence of more than 80 x 10(9)/l blood platelets were studied retrospectively. 72 patients had repeated bleeding times between 10 and 20 min or one or more measurements exceeding 20 min, and were considered to have an unquestionable platelet dysfunction. 39 (54%) of these 72 patients were receiving large doses of antibiotics. Nearly one half of the patients on antibiotics had a bleeding tendency, but most of these patients had additional features that may have interfered with platelet function, or a coagulation defect. In the remaining 33 patients, the prolonged bleeding time was associated with von Willebrand's disease, liver disease, leukaemia/myeloproliferative disease, paraproteinaemia or aspirin ingestion. High doses of penicillin seem to be the most common cause of qualitative platelet disorders in general hospital practice.
CONJUNCTIVAL BLEEDING IN OSLER'S DISEASE WITH ASSOCIATED PLATELET DYSFUNCTION: A Case Report
AbstractA patient with Osler's disease (hereditary haemorrhagic telangiectasia) was admitted to hospital because of obstinate, profuse conjuctival bleeding occurring without any known preceding rrauma. Extensive examination of the haemostatic mechanism revealed an impaired platelet function reflected in defective platelet aggregation by ADP, collagen adrenalin and defective clot retraction. This platelet dysfunction, whose association with conjunctival telangiectasia was hitherto unknown, impaired the patient's already deficient primary haemostasis following the vascular anomaly and apparently contributed to the severity of the bleeding which could only be checked surgically. The findings seem to warrant investigation of the platelet function in patients with Osler's disease. In the event of platelet dysfunction drugs, such as acetylsalicylic acid (aspirin), indomethacin, dextrans as well as transfusions with bank blood are contraindicated.
Reduced Platelet Activity in Patients with Acute Intracranial Hemorrhage
AbstractBACKGROUND: Acquired platelet dysfunction is a common element of trauma-induced coagulopathy and has been linked to increased mortality. The aim of the study was to describe the prevalence of platelet dysfunction in patients with acute intracranial bleeding. METHODS: Patients diagnosed with acute intracranial bleeding were screened for eligibility. Patients with an urgent need for craniotomy were enrolled in this prospective monocentric study. Platelet function analyses using multiple electrode aggregometry (TRAPtest, ASPItest and ADPtest) and conventional coagulation tests were performed. The area under the aggregation curves of the ASPItest and ADPtest were defined as primary outcome variables. RESULTS: Seventy-seven patients were screened for eligibility, and 49 patients were ultimately enrolled in the study. In 14 patients (29%), clinically relevant platelet dysfunction was observed. Of those, 8 patients were treated with antiaggregatory medication at the time of study inclusion. Six patients (12%) were diagnosed with acute acquired platelet dysfunction. CONCLUSIONS: Decreased platelet function was present in nearly one-third of patients with acute intracranial bleeding. Hemotherapy algorithms for the treatment of coagulopathy in this cohort should incorporate aggregometric measures to enable rapid goal-directed therapy.
Cambridge University Press eBooks · 2001 · 1 citations
Clinical approach to the bleeding patient
AbstractReduced 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.
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.
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.
