DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for blood coagulation disease — screening already-approved drugs against its 44-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleBlood coagulation disease maps to a 44-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 blood coagulation 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
ABO, alpha 1-3-N-acetylgalactosaminyltransferase and alpha 1-3-galactosyltransferase (ABO) — ABO 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 6-deoxy-alpha-l-galactopyranosyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4Y63 · 1.3 Å · ligand octyl 2-O-(6-deoxy-alpha-L-galactopyranosyl)-beta-D-galactopyranoside (BHE). Experimental structure, not a prediction.
What the evidence adds up to
Massive transfusion protocols exist at a relatively small number of large trauma centres. Most are designed to treat existing coagulopathy, though the evidence suggests prevention is superior to treatment. Simple fixed ratios such as 1:1:1 red blood cells to plasma to platelets are associated with improved outcome, and the authors propose that such a standard protocol could foster multicentre research. In German trauma centres between 2002 and 2009, the fresh frozen plasma to red blood cell ratio increased from 0.65 to 0.75 and the platelet to red blood cell ratio from 0.04 to 0.09, while use of haemostatic drugs rose from 43.4% of patients in 2005 to 60.7% in 2009. Fibrinogen concentrate use increased from 17.0% to 45.6% and recombinant factor VIIa from 1.9% to 6.3%. Mortality rates remained unchanged over the eight-year period. The authors note that grades of evidence remain low for most of these changes and call for randomised controlled trials.
In patients with haemophilia who develop cardiovascular disease, antithrombotic treatment currently relies on expert opinion and adaptation of guidelines for non-haemophilic patients, because no specific evidence-based guidelines exist for patients with coagulation defects. Replacement therapy with the deficient coagulation factor should be tailored to control the increased bleeding risk from antiplatelet and anticoagulant drugs. For acquired coagulation factor inhibitors, such as factor V inhibition causing severe bleeding, no clear treatment guidelines exist. One case report describes a patient with cerebral haemorrhage who received corticosteroids, intravenous immunoglobulins, rituximab, cyclophosphamide and recombinant factor VIIa, and achieved full recovery despite poor initial prognosis.
Among 41 patients who developed disseminated intravascular coagulation after haematopoietic stem cell transplantation, the 23 treated after 2008 with recombinant human soluble thrombomodulin had significantly improved clinical outcomes at day 100 and prolonged overall survival compared with the 11 treated with heparin or antithrombin III concentrate (P = 0.044). Seven patients received no anticoagulant therapy. For rare congenital coagulation disorders, single-factor concentrates are the therapy of choice, and orphan drug legislation has been developed to stimulate production.
What is still missing are randomised controlled trials for blood component ratios and haemostatic drugs in trauma, specific evidence-based guidelines for antithrombotic management in haemophilia, and clear treatment protocols for acquired coagulation factor inhibitors. The mortality data from the German trauma registry show that despite more aggressive coagulation support, survival has not improved, underscoring the need for better patient stratification and trial design rather than simply more products.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
The Journal of Trauma: Injury, Infection, and Critical Care · 2006 · 447 citations
Massive Transfusion Practices Around the Globe and a Suggestion for a Common Massive Transfusion Protocol
AbstractBACKGROUND: Massive transfusion, the administration of 10 to more than 100 units of red blood cells (RBC) in less than 24 hours, can be a life saving therapy in the treatment of severe injury. The rapid administration of large numbers of RBC, along with sufficient plasma and platelets to treat or prevent coagulopathy, is frequently a disorderly process. Patient care and collaborative research might be aided with a common protocol. METHODS: The authors polled trauma organizations and trauma centers to find examples of massive transfusion protocols. The goals and ease of use of these protocols were evaluated. RESULTS: Massive transfusion protocols exist at a relatively small number of large and well-organized trauma centers. Most of these protocols are designed to treat pre-existing and/or ongoing coagulopathy. CONCLUSIONS: The evidence would suggest that prevention of coagulopathy is superior to its treatment. Simple ratios such as 1:1:1 RBC:plasma:platelets have the benefit of ease of use and the relatively higher plasma and platelet doses appear to be associated with improved outcome. Such a standard protocol can foster multicenter research on resuscitation and hemorrhage control. The fixed volume ratios might allow the number and rate of administered units of RBC to be used as surrogates for blood loss and primary treatment effect.
Expert Opinion on Pharmacotherapy · 2012 · 25 citations
Management of antithrombotic therapy for acute coronary syndromes and atrial fibrillation in patients with hemophilia
AbstractINTRODUCTION: Patients with hemophilia now have a life expectancy very close to that of the unaffected male population and, hence, are at risk of developing the classic age-related morbidities, i.e., cardiovascular diseases. The peculiarity of the management of these diseases in hemophilia is that antithrombotic drugs impinge on the already compromised hemostasis of these lifelong bleeders. AREAS COVERED: This opinion article outlines the strategies we have developed, based on our clinical experience, for the antithrombotic treatment of two common cardiovascular diseases - acute coronary syndromes and chronic atrial fibrillation - in patients with hemophilia A and B. EXPERT OPINION: In the absence of specific evidence-based guidelines for patients with coagulation defects, antithrombotic treatment is currently based on expertise and adaptation of the guidelines developed for non-hemophilic patients. Replacement therapy should be tailored with the deficient coagulation factor so as to control the increased risk of bleeding inherent in the use of antiplatelet and anticoagulant drugs.
The Journal of Trauma: Injury, Infection, and Critical Care · 2012 · 18 citations
Coagulation management of bleeding trauma patients is changing in German trauma centers
AbstractBACKGROUND: Recent findings have emphasized the need for early and aggressive coagulation support in bleeding trauma patients. This study aimed to examine whether blood component transfusion and hemostatic drug administration during acute trauma care have changed in daily practice during the recent years. METHODS: The multicenter trauma registry of the German Society for Trauma was retrospectively analyzed for primarily admitted patients older than 16 years with an Injury Severity Score ≥ 16 who had received at least five red blood cell (RBC) units between emergency room arrival and intensive care unit admission. Administration of fresh frozen plasma and platelet units has been documented since 2002, and use of hemostatic drugs since 2005. RESULTS: From 2002 until 2009 (n = 2,813), the fresh frozen plasma:RBC ratio increased from 0.65 to 0.75 (p = 0.02) and the platelet:RBC ratio from 0.04 to 0.09 (p < 0.0001). A constant increase was also observed regarding the overall use of hemostatic drugs (n = 1,811; 2005-2009) as these were administered to 43.4% of the patients in 2005 and to 60.7% in 2009 (p < 0.0001). Especially, the administration of fibrinogen concentrate (2005: 17.0%, 2009: 45.6%; p < 0.0001) and recombinant factor VIIa (2005: 1.9%, 2009: 6.3%; p = 0.04) showed a marked increase. However, mortality rates remained unchanged during the 8-year study period. CONCLUSIONS: The therapy of bleeding trauma patients has changed in Germany during the recent years toward more aggressive coagulation support. This development continues although grades of evidence are still low regarding most of the changes reported in our study. Randomized controlled trials are needed with respect to blood component therapy using predefined ratios and to the administration of hemostatic drugs commonly used for the severely injured.
European Journal Of Haematology · 2013 · 18 citations
Effect of recombinant human soluble thrombomodulin on clinical outcomes of patients with coagulopathy after hematopoietic stem cell transplantation
AbstractFrom 2001 to 2012, 71 individuals with hematological diseases received HSCT in our institution. Of these, 41 developed disseminated intravascular coagulation (DIC) in association with various underlying conditions. The patients who developed DIC after 2008 (n = 23) were treated by recombinant human soluble thrombomodulin (rTM), and the others (n = 11) were treated by either heparin and/or antithrombin III concentrate. Seven patients did not receive any anticoagulant therapy. Of note, treatment for coagulopathy by rTM significantly improved clinical outcomes of patients at day 100 and dramatically prolonged their overall survival (P = 0.044). Taken together, rTM is useful to improve clinical outcomes of transplant recipients with coagulopathy.
Balkan Medical Journal · 2017 · 3 citations · open access
Successful Outcome of Severe Intra-cerebral Bleeding Associated with Acquired Factor V Inhibition: Utilization of Multiple Therapeutic Agents
AbstractBACKGROUND: Acquired coagulation factor inhibitors are antibodies that either inhibit activity or increase the clearance of a clotting factor and lead to an increased risk of bleeding. Most of the time, the disorder is attributed to factor VIII inhibition (acquired haemophilia A); however, other coagulation factors could also be implicated. CASE REPORT: Herein, we report an interesting case of a patient who underwent coronary artery bypass grafting and received antibiotic treatment after surgery with third generation cephalosporin. A month later, he presented with extreme bleeding diathesis and cerebral haemorrhage. Following a thorough clinical and laboratory investigation, an acquired factor V inhibitor was diagnosed. The patient received treatment with corticosteroids, intravenous immunoglobulins, anti-CD20 monoclonal antibodies (rituximab), cyclophosphamide and recombinant factor VIIa. Finally, despite the poor initial prognosis, the patient managed to achieve a full recovery. CONCLUSION: As there are no clear guidelines on acquired coagulation inhibitor treatment, reports of such cases could offer insight for future therapy choices. The case was unique because the treatment regimen included a combination of multiple therapeutic agents including rituximab.
Expert Opinion on Orphan Drugs · 2015 · 2 citations
Factor concentrates for rare congenital coagulation disorders: where are we now?
AbstractIntroduction: Current treatments of rare coagulation disorders (RCD) include fresh frozen plasma, cryoprecipitates, prothrombin complex concentrates, plasma-derived concentrates and recombinant products. Single-factor concentrates are the therapy of choice since they allow administration of only the defective protein and reduce the risk of transfusion adverse effects. Specific legislation has been developed to stimulate the development of drugs for such rare diseases, the so-called “orphan drugs.”
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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