DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for thrombophilia — screening already-approved drugs against its 34-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleThrombophilia maps to a 34-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 thrombophilia 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
A 2012 Cochrane review found no randomised or controlled clinical trials that assessed whether thrombophilia testing after venous thromboembolism reduces the risk of recurrent events. The authors concluded that no such trials could be identified. A 2013 retrospective study of 392 children with venous thromboembolism reported that thrombophilia rates were low in both inpatients and outpatients; central venous line presence was significantly associated with not being tested. The study did not report survival or recurrence rates.
A 2022 cross-sectional study of 3686 patients referred for thrombophilia testing at a Swiss tertiary hospital found that only 33% of tests were adherent to internal guidelines. Test results influenced treatment decisions in 5.1% of guideline-adherent work-ups and 9.7% of non-adherent work-ups, an absolute difference of 4.3%. The authors concluded that adherence to guidelines was poor and did not affect treatment decisions. A separate 2022 retrospective cohort study of 3550 patients from the same centre reported that 34% had at least one thrombophilia finding, and 10% had high-risk thrombophilia. Appropriate anticoagulation decisions occurred in 6% of work-ups overall (13% of low-risk and 27% of high-risk cases), while 5% of negative results led to inappropriate withholding of anticoagulation. Among 2492 patients followed for a median of 49 months, high-risk thrombophilia was associated with higher risk of subsequent venous thromboembolism and pregnancy-related morbidity. The authors stated that the work-up had limited usefulness in clinical decision-making.
No drug is mentioned in any of these abstracts. What remains missing is any randomised trial of testing versus no testing, prospective validation of selection criteria that might increase the therapeutic impact of thrombophilia testing, and evidence that testing changes patient outcomes such as mortality or recurrence rates in a controlled setting.
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 · 62 citations · open access
Thrombophilia testing for prevention of recurrent venous thromboembolism
AbstractBACKGROUND: Tests for thrombophilia are being performed on a large scale in people after venous thromboembolism (VTE) even though the benefits of testing are still subject to debate. The most important benefit would be a reduction in the risk of recurrent VTE due to the use of additional prophylactic measures. This is an update of a review first published in 2009. OBJECTIVES: The objective of this review was to assess the benefit of testing for thrombophilia after VTE in terms of risk reduction of recurrent VTE. SEARCH METHODS: For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched May 21 2012) and CENTRAL (2012, Issue 5). The authors searched MEDLINE and EMBASE. SELECTION CRITERIA: Randomized controlled trials (RCTs) and controlled clinical trials (CCTs) that compared the rate of recurrent VTE in participants with VTE who were tested for thrombophilia with the rate in participants with VTE who were not tested were eligible. DATA COLLECTION AND ANALYSIS: We planned to extract data from identified studies using data extraction forms. MAIN RESULTS: No studies were included because no RCTs or CCTs could be identified. AUTHORS' CONCLUSIONS: There are currently no randomized controlled trials or controlled clinical trials that have assessed the benefit(s) of testing for thrombophilia on the risk of recurrent VTE.
Thrombophilia testing in children: A 7 year experience
AbstractBACKGROUND: Incidence of venous thromboembolism (VTE) in children is reported to be increasing. We examined thrombophilia testing results in children with VTE that presented in inpatient and outpatient settings to explore patterns of thrombophilia testing. PATIENTS/METHODS: Children, ages 0-20 years with VTE seen at our institution from Jan 2005 to Apr 2012 were studied retrospectively. All patients with VTE confirmed by imaging were eligible and the presence of significant risk factors was evaluated. Thrombophilia was diagnosed if >1 tests confirmed: persistently low protein C (PC), protein S (PS), and antithrombin (AT) following VTE resolution, persistent antiphospholipid antibodies (APA) positivity >12 weeks from first test, factor V Leiden (FVL) and prothrombin mutation (PTm) hetero- or homozygosity, elevated plasminogen activator inhibitor (PAI-1) levels with 4G/5G or 4G/4G polymorphisms, methylene tetrahydrofolate reductase (MTHFR) polymorphisms with elevated fasting homocysteine levels. RESULTS: Three hundred ninety-two patients met inclusion criteria. At least one test was ordered in 157/239 inpatients. All 153 outpatients had >1 test ordered. Thrombophilia rate differences between inpatients and outpatients did not reach statistical significance except for PC deficiency, which was significantly higher in outpatients. Of inpatients, central venous line (CVL) was significantly associated with not having tests done (P < 0.0022). CONCLUSIONS: This study of pediatric VTE demonstrated a low thrombophilia rate in both inpatient and outpatient populations. The role of testing in other pediatric patients should be further explored.
Thrombosis Research · 2022 · 14 citations · open access
Adherence to thrombophilia testing guidelines and its influence on anticoagulation therapy: A single-center cross-sectional study
AbstractINTRODUCTION: The collected evidence on thrombophilia guidelines is scarce and data about their impact on clinical decisions are unknown. We aimed to investigate the adherence to thrombophilia testing guidelines, its therapeutic impact in patients with guideline-adherent and non-adherent testing and identify the patients' clinical characteristics mostly associated with treatment decisions. MATERIALS AND METHODS: We conducted a single-center cross-sectional study of patients referred for thrombophilia testing at the outpatient clinic of a tertiary hospital between 01/2010-10/2020. We systematically evaluated the adherence of thrombophilia testing to internal guidelines and the influence of test results on anticoagulation therapy. Using multivariable logistic regression, we evaluated the association between clinical characteristics and influence of thrombophilia tests on anticoagulation therapy in the entire cohort and by indication for referral. RESULTS: Of 3686 included patients, mostly referred for venous thromboembolism (2407, 65 %) or arterial thrombosis (591, 16 %), 3550 patients (96 %) underwent thrombophilia testing. Indication for testing was according to guidelines in 1208 patients (33 %). Test results influenced treatment decisions in 56 of 1102 work-ups (5.1 %) that were adherent to guidelines, and in 237 of 2448 (9.7 %) non-adherent work-ups (absolute difference, 4.3 %; 95 % confidence interval, 2.9-6.3 %). Age < 50 years, female sex, absence of risk factors and co-morbidities, weakly provoked venous thromboembolism and referral indication other than venous thromboembolism were associated with influence on anticoagulation therapy. CONCLUSIONS: Adherence to guidelines for thrombophilia testing was poor and did not have an impact on treatment decisions. Refinement of selection criteria is needed to increase the therapeutic impact of thrombophilia testing.
Journal of Clinical Medicine · 2022 · 9 citations · open access
Thrombophilia Impact on Treatment Decisions, Subsequent Venous or Arterial Thrombosis and Pregnancy-Related Morbidity: A Retrospective Single-Center Cohort Study
Abstract(1) Background: Thrombophilia testing utility has remained controversial since its clinical introduction, because data on its influence on treatment decisions are limited. (2) Methods: We conducted a single-center retrospective cohort study of 3550 unselected patients referred for thrombophilia consultation at the Bern University Hospital in Switzerland from January 2010 to October 2020. We studied the influence of thrombophilia testing results on treatment decisions and evaluated the association between thrombophilia and thromboembolic and pregnancy-related morbidity events after testing up to 03/2021. (3) Results: In 1192/3550 patients (34%), at least one case of thrombophilia was found and 366 (10%) had high-risk thrombophilia. A total of 211/3550 (6%) work-ups (111/826 (13%) with low-risk thrombophilia and 100/366 (27%) with high-risk thrombophilia) led to an appropriate decision to extend or initiate anticoagulation, and 189 (5%) negative results led to the withholding of anticoagulation therapy inappropriately. A total of 2492 patients (69%) were followed up for >30 days, with a median follow-up of 49 months (range, 1−183 months). Patients with high-risk thrombophilia had a higher risk of subsequent venous thromboembolic events and pregnancy-related morbidity compared to those without thrombophilia. (4) Conclusions: Our study demonstrated the limited usefulness of thrombophilia work-up in clinical decision-making. High-risk thrombophilia was associated with subsequent venous thromboembolism and pregnancy-related morbidity.
Journal of Blood Medicine · 2022 · 8 citations · open access
Apixaban Use in Patients with Protein C and S Deficiency: A Case Series and Review of Literature
AbstractBackground: Historically, warfarin was the mainstay anticoagulant agent to manage patients presenting with thrombotic disorders caused by Protein C or S deficiency. Several direct oral anticoagulants (DOACs) were introduced over the past decade. They showed superiority over warfarin in patients with venous thromboembolism in many landmark trials. Insufficient data are available that examine the outcome of utilizing apixaban in patients with protein S deficiency induce thrombosis. Cases Presentation: We reported the clinical outcomes of utilizing apixaban in four patients with systemic thrombosis caused by protein C or S deficiency who presented to a tertiary hospital in Riyadh, Saudi Arabia. Four patients exhibited typical features of thrombotic events. After confirming the diagnosis, one patient was initially started on apixaban, and the other three patients were converted from warfarin to apixaban. Three of the four patients tolerated the apixaban during the follow-up period. Additionally, they did not have any bleeding or thrombotic complications. However, one patient developed recurrent thrombotic events despite switching to different type of DOAC and was ultimately transitioned back to warfarin. Conclusion: Based on the available emerging evidence and our case series, the use of apixaban could be effective in preventing recurrent thrombotic events in patients with inherited thrombophilia without safety concerns. Further, large studies are warranted to investigate the safety and efficacy of apixaban in these population.
Open Access CRIS of the University of Bern · 2022 · 0 citations · open access
Thrombophilia Impact on Treatment Decisions, Subsequent Venous or Arterial Thrombosis and Pregnancy-Related Morbidity: A Retrospective Single-Center Cohort Study.
Abstract(1) Background: Thrombophilia testing utility has remained controversial since its clinical introduction, because data on its influence on treatment decisions are limited. (2) Methods: We conducted a single-center retrospective cohort study of 3550 unselected patients referred for thrombophilia consultation at the Bern University Hospital in Switzerland from January 2010 to October 2020. We studied the influence of thrombophilia testing results on treatment decisions and evaluated the association between thrombophilia and thromboembolic and pregnancy-related morbidity events after testing up to 03/2021. (3) Results: In 1192/3550 patients (34%), at least one case of thrombophilia was found and 366 (10%) had high-risk thrombophilia. A total of 211/3550 (6%) work-ups (111/826 (13%) with low-risk thrombophilia and 100/366 (27%) with high-risk thrombophilia) led to an appropriate decision to extend or initiate anticoagulation, and 189 (5%) negative results led to the withholding of anticoagulation therapy inappropriately. A total of 2492 patients (69%) were followed up for >30 days, with a median follow-up of 49 months (range, 1-183 months). Patients with high-risk thrombophilia had a higher risk of subsequent venous thromboembolic events and pregnancy-related morbidity compared to those without thrombophilia. (4) Conclusions: Our study demonstrated the limited usefulness of thrombophilia work-up in clinical decision-making. High-risk thrombophilia was associated with subsequent venous thromboembolism and pregnancy-related morbidity.
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.
