DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for platelet-type bleeding disorder 15 — 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 15 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 15 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
actinin alpha 1 (ACTN1) — ACTN1 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 2EYI · 1.7 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
A 2007 review of immune thrombocytopenic purpura in adults concluded that most patients tolerate the disease well with little morbidity. Splenectomy was described as the best curative treatment for adults with chronic disease of at least six months. Other treatments such as anti-D, rituximab, or dexamethasone might allow splenectomy to be postponed, possibly indefinitely, if a haemostatic platelet count is reached. The review stated that mortality from bleeding may be relevant only in patients refractory to splenectomy, and that cytotoxic agents should be reserved for bleeding refractory to other treatments. An aggressive approach was justified only for patients with platelet counts below 20 x 10⁹/l and those refractory to splenectomy.
A 2011 study of 46 trauma patients on clopidogrel used a P2Y12 point-of-care assay to measure platelet inhibition. Mean age was 75.9 years; 86.9% of injuries were from falls. Platelet inhibition ranged from 0% to 89%. No deaths occurred, and only two patients had haemorrhagic complications (increased intracranial haemorrhage), one from the 0% inhibition group and one from the >30% inhibition group. The authors noted that a large percentage of patients had undetectable or low platelet inhibition despite reportedly taking clopidogrel, suggesting non-response or non-compliance. They concluded that reversal therapies such as platelet transfusions or desmopressin would be unlikely to benefit this group.
A 2014 modelling analysis of the TOPPS trial, which enrolled 600 patients with haematologic malignancies, found that 46% of 560 patients with complete follow-up had at least one WHO grade 2-4 bleed in 30 days. Baseline factors associated with more days of bleeding were allogeneic HSCT or chemotherapy treatment plan, female sex, and assignment to the no-prophylaxis arm. A platelet count below 10 x 10⁹/l on each of the previous three days was significantly associated with grade 2-4 bleeding (hazard ratio 1.5, 95% CI 1.1 to 2.0, p=0.009). Fever was also a significant risk factor: patients with a temperature of at least 38°C had the highest hazard of a grade 2-4 bleed (HR 1.7, 95% CI 1.3 to 2.4) compared to those with temperature below 37.5°C. Minor bleeding did not predict more severe bleeds. The authors concluded that clinically stable patients without fever undergoing autologous HSCT had the lowest risk of bleeding and might benefit least from prophylactic platelet transfusions.
A 2001 chapter on the clinical approach to the bleeding patient stated that reduced platelet count or function is typically expressed as a bleeding problem, but emphasised that the differential diagnosis is broader than just platelet disorders. It described a systematic approach involving urgent measures, inspection for subcutaneous bleeding, focused history, physical examination, and initial laboratory tests. What remains missing for platelet-type bleeding disorder 15 specifically are prospective studies that stratify patients by validated risk factors (platelet count burden, fever, treatment plan) to guide targeted transfusion or other interventions, and trials that test whether such stratification reduces bleeding without increasing harm.
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.
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.
Cardiovascular Drugs and Therapy · 2009 · 9 citations · open access
Oral Antiplatelet Therapy for Acute and Chronic Management of NSTE ACS: Residual Ischemic Risk and Opportunities for Improvement
AbstractINTRODUCTION: Non-ST-segment elevation acute coronary syndromes (NSTE ACS) are highly prevalent in the United States and globally, and are associated with significant morbidity and mortality. DISCUSSION: The key role of platelet-mediated thrombosis in the pathogenesis of NSTE ACS is confirmed by the proven clinical benefits of antiplatelet agents (aspirin and a P2Y(12) adenosine diphosphate [ADP] receptor antagonist) in this setting. Despite the documented advantages and broad use of antiplatelet therapy, the long-term morbidity and mortality rates remain significant, and the bleeding risk remains substantial. Residual risk can be attributed, at least in part, to the fact that thrombosis continues in the presence of current treatments because aspirin and P2Y(12) ADP receptor antagonists each block only one of multiple platelet activation pathways, and thus do not impact other platelet activation pathways, such as the one triggered by interaction of thrombin with protease-activated receptor (PAR)-1, thereby exposing patients to continued accumulation of thrombotic events. CONCLUSION: These considerations suggest that novel therapies with a different mechanism of action, when used in combination with current antiplatelet agents, may provide more comprehensive inhibition of platelet activation and additional reductions in morbidity and mortality, potentially without incremental bleeding risk.
Risk Factors for Bleeding: A Modelling Analysis of the TOPPS Randomized Controlled Trial of Prophylactic Platelet Transfusion
AbstractAbstract Background The recent UK/Australia TOPPS trial of prophylactic platelet transfusions (PltTx) recruited 600 patients with hematologic malignancies and reported that for all patients prophylaxis led to lower rates of World Health Organization (WHO) grade 2-4 bleeding. However, between 43 and 50% of all patients in the trial had some grade 2-4 bleeding, and there was evidence that the effect of PltTx varied by patient subgroup. Given the limited effectiveness of prophylactic PltTx to reduce bleeding risk, the issue remains whether other patient factors or clinical characteristics are more important prognostic factors for bleeding. Methods Statistical models were developed to explore risk factors for bleeding in all patients and in the large subgroup of autologous HSCT patients in the TOPPS dataset. Models were developed for baseline characteristics at presentation and for recurrent analysis of bleeding to assess the risks of grade 2-4 bleeding on any given day, accounting for previous bleeds in the 30 day time period. Additional analyses were undertaken to explore the severity and burden of thrombocytopenia, and importance of fever as a risk factor for bleeding. Results Baseline characteristic data were complete for 592 patients and 560 of these had complete follow-up data for the 30 days of the study. 256 (46%) of the 560 patients had at least one grade 2-4 bleed in the 30 days. Figure 1 shows the results of the main multivariate modeling of baseline characteristics associated with number of cumulative days bleeding. Treatment plan (alloHSCT/chemo), female sex and treatment arm (no-prophylaxis) were all found to be significantly associated with increased number of days of bleeding. Relevance of a low plt count over the previous 3 days was investigated for study days 4 to 30 (6712 bleeding records, 588 patients). There was evidence of a significant association between bleeding and a plt count <10x109/L for each of the previous 3 days (hazard ratio 1.5, 95% CI: 1.1 to 2.0, p=0.009). Number of days out of the previous 3 with a plt count <10x109/L was significantly associated with a grade 2-4 bleed (p<0.0001) and there was a significant interaction with treatment plan (p=0.005) (Fig 2). Additional analysis investigated relevance of the highest temperature in the previous 3 days for study days 4 to 30 (n=4,277, 469 patients). After adjusting for the factors in Figure 1, plt count on the preceding day, and red cell transfusion in previous 3 days, a significant association was found between highest temperature and hazard of grade 2-4 bleeding (p=0.03). Patients with a temp of at least 380C had the highest hazard of a grade 2-4 bleed (HR: 1.7, 95% CI: 1.3 to 2.4, compared to temp <37.50C). There was no evidence that grade 1 bleeding predicted a grade 2-4 bleed in either the Cox proportional hazards model or the risk-adjusted recurrent event analysis. Discussion We need to better understand factors identifying patients at greater or lesser risk of bleeding. Our findings confirm the presence of a sub-group effect, with differences for baseline characteristics between autoHSCT versus alloHSCT/chemotherapy patients. Severity and burden of thrombocytopenia was identified as a risk factor for bleeding. There was a significant association between highest temperature and hazard of a grade 2-4 bleed, but there was no evidence of minor bleeding predicting more severe bleeds. Clinically stable patients without fever and undergoing autologous HSCT have the lowest risk of bleeding and may benefit least from prophylactic platelet transfusions. Prospective studies are required to address the usefulness of risk factors to support better targeted plt transfusions. Figure 1 Multivariate modelling of baseline characteristics associated with number of days bleeding Figure 1. Multivariate modelling of baseline characteristics associated with number of days bleeding Figure 2 Risk-adjusted hazard ratios for a grade 2-4 bleed for the number of days with a platelet count <10x109/L, by treatment arm Figure 2. Risk-adjusted hazard ratios for a grade 2-4 bleed for the number of days with a platelet count <10x109/L, by treatment arm Disclosures No relevant conflicts of interest to declare.
TURKISH JOURNAL OF MEDICAL SCIENCES · 2016 · 5 citations · open access
The effect of methylprednisolone treatment on fibrinolysis, thecoagulation system, and blood loss in cardiac surgery
AbstractBACKGROUND/AIM: The purpose of this study was to examine steroid pretreatment in order to decrease postoperative coagulopathy disorders and bleeding. MATERIALS AND METHODS: In this randomized double-blinded study, the efficacy of low versus high doses of methylprednisolone on the coagulation system and postoperative bleeding was compared in patients who were undergoing cardiac surgery with cardiopulmonary bypass (CPB). The platelet response to agonists, D-dimer concentration, tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI-1) antigens, and platelet receptors CD42b, CD62P, and CD41a were evaluated. RESULTS: The platelet response to agonists was reduced. The mean concentrations of D-dimer and tPA antigen increased although PAI-1 concentration did not show any significant changes following heparin neutralization. Postoperative expression of CD42b showed no changes in comparison with preoperation values in both groups. There was a significant increase in the expression of CD62P with a methylprednisolone dose of 15 mg/kg, while there was just a slight increase with a dose of 5 mg/kg. CD41a, as a fibrinogen receptor, was increased significantly after CPB in both groups. Significant data were shown in decreasing blood loss with a high dose of methylprednisolone. CONCLUSION: Methylprednisolone at a dose of 15 mg/kg reduced bleeding, probably by increasing CD62P after heparin neutralization, which can activate platelet activation in favor of better hemostasis.
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.
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