DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for platelet-type bleeding disorder 10 — screening already-approved drugs against its 2-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 10 maps to a 2-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 10 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
CD36 molecule (CD36 blood group) (CD36) — CD36 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 plmdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5LGD · 2.07 Å · ligand PALMITIC ACID (PLM). Experimental structure, not a prediction.
What the evidence adds up to
In a 2012 Cochrane review of 13 completed trials (2331 participants) comparing prophylactic platelet transfusion strategies in haematological patients, no statistical difference in clinically significant bleeding was found between prophylactic and therapeutic-only transfusion (RR 1.66; 95% CI 0.9 to 3.04), though the confidence interval was wide. Lower platelet count thresholds (10 x 10⁹/L versus 20 x 10⁹/L) showed no statistical difference in the number of participants with clinically significant bleeding (RR 1.35; 95% CI 0.95 to 1.9), but bleeding occurred on fewer days in the higher-threshold group (RR 1.72; 95% CI 1.33 to 2.22). Different platelet doses did not affect the number of patients with significant bleeding (RR 1.02; 95% CI 0.93 to 1.11) or life-threatening bleeding (RR 1.87; 95% CI 0.86 to 4.08). One small trial found prophylactic platelet transfusion reduced the risk of significant bleed compared to platelet-poor plasma (RR 0.47; 95% CI 0.23 to 0.95). The authors concluded there is no evidence that a prophylactic platelet transfusion policy prevents bleeding, and that the evidence for a 10 x 10⁹/L threshold being equivalent to 20 x 10⁹/L is not definitive.
A 2017 observational cohort study of 2256 critically ill patients with thrombocytopenia found that adjusted rates of major bleeding were not statistically different between those who received platelet transfusions and those who did not (hazard ratio 0.85; 95% CI 0.42 to 1.72). Only 71 patients (3.1%) received platelet transfusions, and the median post-transfusion platelet count increment was 20 x 10⁹/L at 3.5 hours. The study found no significant association between platelet transfusion and thrombosis or death in the ICU, but the authors noted inferences were limited by the small number of transfused patients.
A 2007 review of immune thrombocytopenic purpura in adults stated that most patients have a generally well-tolerated disease with little morbidity, and that splenectomy remains the best curative treatment for chronic disease. Mortality from bleeding may be relevant only in patients refractory to splenectomy. The review recommended an aggressive therapeutic approach only for patients with platelet counts below 20 x 10⁹/L and those refractory to splenectomy. A 2011 article on reversing antiplatelet drug effect noted there are no guidelines for management and described an approach based solely on personal experience and very limited published data. A 2011 study of 46 trauma patients on clopidogrel found platelet inhibition ranged from 0% to 89%, with only two patients having haemorrhagic complications, and suggested that reversal therapies such as platelet transfusions would be unlikely to benefit patients with undetectable or low platelet inhibition.
What is still missing are adequately powered randomised trials comparing prophylactic versus therapeutic platelet transfusion strategies in haematological patients, clinical trials in critically ill thrombocytopenic patients to investigate potential haemostatic benefit and harms of platelet transfusions, and studies that stratify patients by degree of platelet inhibition to guide reversal therapies.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Cochrane Database of Systematic Reviews · 2012 · 120 citations
Prophylactic platelet transfusion for prevention of bleeding in patients with haematological disorders after chemotherapy and stem cell transplantation
AbstractBACKGROUND: Platelet transfusions are used in modern clinical practice to prevent and treat bleeding in thrombocytopenic patients with bone marrow failure. Although considerable advances have been made in platelet transfusion therapy in the last 40 years, some areas continue to provoke debate especially concerning the use of prophylactic platelet transfusions for the prevention of thrombocytopenic bleeding. OBJECTIVES: To determine the most effective use of platelet transfusion for the prevention of bleeding in patients with haematological disorders undergoing chemotherapy or stem cell transplantation. SEARCH METHODS: This is an update of a Cochrane review first published in 2004. We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL Issue 4, 2011), MEDLINE (1950 to Nov 2011), EMBASE (1980 to Nov 2011) and CINAHL (1982 to Nov 2011), using adaptations of the Cochrane RCT search filter, the UKBTS/SRI Transfusion Evidence Library, and ongoing trial databases to 10 November 2011. SELECTION CRITERIA: RCTs involving transfusions of platelet concentrates, prepared either from individual units of whole blood or by apheresis, and given to prevent bleeding in patients with haematological disorders. Four different types of prophylactic platelet transfusion trial were included. DATA COLLECTION AND ANALYSIS: In the original review one author initially screened all electronically derived citations and abstracts of papers, identified by the review search strategy, for relevancy. Two authors performed this task in the updated review. Two authors independently assessed the full text of all potentially relevant trials for eligibility. Two authors completed data extraction independently. We requested missing data from the original investigators as appropriate. MAIN RESULTS: There were 18 trials that were eligible for inclusion, five of these were still ongoing.Thirteen completed published trials (2331 participants) were included for analysis in the review. The original review contained nine trials (718 participants). This updated review includes six new trials (1818 participants).Two trials (205 participants) in the original review are now excluded because fewer than 80% of participants had a haematological disorder.The four different types of prophylactic platelet transfusion trial, that were the focus of this review, were included within these thirteen trials.Three trials compared prophylactic platelet transfusions versus therapeutic-only platelet transfusions. There was no statistical difference between the number of participants with clinically significant bleeding in the therapeutic and prophylactic arms but the confidence interval was wide (RR 1.66; 95% CI 0.9 to 3.04).The time taken for a clinically significant bleed to occur was longer in the prophylactic platelet transfusion arm. There was a clear reduction in platelet transfusion usage in the therapeutic arm. There was no statistical difference between the number of participants in the therapeutic and prophylactic arms with platelet refractoriness, the only adverse event reported.Three trials compared different platelet count thresholds to trigger administration of prophylactic platelet transfusions. No statistical difference was seen in the number of participants with clinically significant bleeding (RR 1.35; 95% CI 0.95 to 1.9), however, this type of bleeding occurred on fewer days in the group of patients transfused at a higher platelet count threshold (RR 1.72; 95% CI 1.33 to 2.22).The lack of a difference seen for the number of participants with clinically significant bleeding may be due to the studies, in combination, having insufficient power to demonstrate a difference, or due to masking of the effect by a higher number of protocol violations in the groups of patients with a lower platelet count threshold. Using a lower platelet count threshold led to a significant reduction in the number of platelet transfusions used. There were no statistical differences in the number of adverse events reported between the two groups.Six trials compared different doses of prophylactic platelet transfusions. There was no evidence to suggest that using a lower platelet transfusion dose increased: the number of participants with clinically significant (WHO grade 2 or above) (RR 1.02; 95% CI 0.93 to 1.11), or life-threatening (WHO grade 4) bleeding (RR 1.87; 95% CI 0.86 to 4.08). A higher platelet transfusion dose led to a reduction in the number of platelet transfusion episodes, but an increase in total platelet utilisation. Only one adverse event, wheezing after transfusion, had a significantly higher incidence when standard and high dose transfusions were compared but this difference was not seen when low dose and high dose transfusions were compared. It is therefore likely to be a type I error (false positive).One small trial compared prophylactic platelet transfusions versus platelet-poor plasma. The risk of a significant bleed was decreased in the prophylactic platelet transfusion arm (RR 0.47; 95% CI 0.23 to 0.95) and this was statistically significant.All studies had threats to validity; the majority of these were due to methodology of the studies not being described in adequate detail.Although it was not the main focus of the review, it was interesting to note that in one of the pre-specified sub-group analyses (treatment type) two studies showed that patients receiving an autologous transplant have a lower risk of bleeding than patients receiving intensive chemotherapy or an allogeneic transplant (RR 0.73, 95% CI 0.65 to 0.82). AUTHORS' CONCLUSIONS: These conclusions refer to the four different types of platelet transfusion trial separately. Firstly, there is no evidence that a prophylactic platelet transfusion policy prevents bleeding. Two large trials comparing a therapeutic versus prophylactic platelet transfusion strategy, that have not yet been published, should provide important new data on this comparison. Secondly, there is no evidence, at the moment, to suggest a change from the current practice of using a platelet count of 10 x 10(9)/L. However, the evidence for a platelet count threshold of 10 x 10(9)/L being equivalent to 20 x 10(9)/L is not as definitive as it would first appear and further research is required. Thirdly, platelet dose does not affect the number of patients with significant bleeding, but whether it affects number of days each patient bleeds for is as yet undetermined. There is no evidence that platelet dose affects the incidence of WHO grade 4 bleeding.Prophylactic platelet transfusions were more effective than platelet-poor plasma at preventing bleeding.
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.
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.
Surgical postoperative bleeding associated with aspirin ingestion
AbstractTwo patients are reported in whom repeated postoperative hematomas appeared to be secondary to aspirin-induced platelet defect. Routine bleeding and clotting studies will not demonstrate this platelet-induced coagulopathy. A previous history of massive aspirin ingestion makes such a coagulopathy a serious consideration, but the platelet defect may occur with small doses of aspirin. Such aspirin ingestion should be viewed with great concern by the neurosurgeon. The defect is treatable by platelet transfusion.
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.
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.
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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